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30488364
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Improvement of thermotolerance in Lachancea thermotolerans using a bacterial selection pressure.
|
The use of thermotolerant yeast strains is an important attribute for a cost-effective high temperature biofermentation processes. However, the availability of thermotolerant yeast strains remains a major challenge. Isolation of temperature resistant strains from extreme environments or the improvements of current strains are two major strategies known to date. We hypothesised that bacteria are potential "hurdles" in the life cycle of yeasts, which could influence the evolution of extreme phenotypes, such as thermotolerance. We subjected a wild-type yeast, Lachancea thermotolerans to six species of bacteria sequentially for several generations. After coevolution, we observed that three replicate lines of yeasts grown in the presence of bacteria grew up to 37 °C whereas the controls run in parallel without bacteria could only grow poorly at 35 °C retaining the ancestral mesophilic trait. In addition to improvement of thermotolerance, our results show that the fermentative ability was also elevated, making the strains more ideal for the alcoholic fermentation process because the overall productivity and ethanol titers per unit volume of substrate consumed during the fermentation process was increased. Our unique method is attractive for the development of thermotolerant strains or to augment the available strain development approaches for high temperature industrial biofermentation.
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10.1007/s10295-018-2107-4
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20392248
|
Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts.
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Different working modes were proposed to explain how bone morphogenetic protein (BMP) type I and II receptors are involved in Smad phosphorylation cascades. In addition, both parathyroid hormone (PTH) and Wnts are also known to regulate phosphorylation of Smads. Here we established a mouse model in which a C-terminal truncated BMP type II receptor (BMPRII) is expressed specifically in osteoblasts as a dominant negative form in the BMP/Smad signaling pathway. Smad1/5/8 phosphorylation levels were reduced in bone marrow stromal cells from the transgenic mice. The sizes of embryos were smaller, and the mineralization of calvarial bones and lumbar vertebrae were delayed in mice expressing the transgene. In adult transgenic mice, total bone volume was reduced with no significant changes observed in cortical bone. Thus, osteoblast-targeted expression of dominant negative BMPRII leads to inhibited Smad1 phosphorylation, delayed skeletal development, and decreased bone formation in the adult mice. This study provides an in vivo tool to study the role of BMPRII in BMP/Smad signaling and the regulation of this pathway by PTH and Wnts.
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10.1111/j.1749-6632.2009.05248.x
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26531167
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Potential advantages of the GuideLiner ® catheter: insights from optical coherence tomography.
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Optical coherence tomography (OCT) has been reported as promising not only for the evaluation of lesion morphology, but also for better clinical outcomes; however, in some cases with severe vessel tortuosity or angulated bifurcation, it is difficult to advance an intravascular imaging catheter. We report a case in which a GuideLiner ® catheter facilitated obtaining better angiographic and OCT images with the sub-selective injection of minimal contrast medium, even in a case with a tortuous vessel or angulated bifurcation. Furthermore, OCT assessment of a vessel through the catheter may be other potential advantage of this device.
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10.1007/s12928-015-0365-x
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22652348
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Visualizing interaction effects: a proposal for presentation and interpretation.
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Interaction terms are often included in regression models to test whether the impact of one variable on the outcome is modified by another variable. However, the interpretation of these models is often not clear. We propose several graphical presentations and corresponding statistical tests alleviating the interpretation of interaction effects. We implemented functions in the statistical program R that can be used on interaction terms in linear, logistic, and Cox Proportional Hazards models. Survival data were simulated to show the functionalities of our proposed graphical visualization methods. The mutual modifying effect of the interaction term is grasped by our presented figures and methods: the combined effect of both continuous variables is shown by a two-dimensional surface mimicking a 3D-Plot. Furthermore, significance regions were calculated for the two variables involved in the interaction term, answering the question for which values of one variable the effect of the other variable significantly differs from zero and vice versa. We propose several graphical visualization methods to ease the interpretation of interaction effects making arbitrary categorizations unnecessary. With these approaches, researchers and clinicians are equipped with the necessary information to assess the clinical relevance and implications of interaction effects. Copyright © 2012 Elsevier Inc. All rights reserved.
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10.1016/j.jclinepi.2012.02.013
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11456016
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Color Doppler imaging of untreated and irradiated choroidal melanomas.
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We examined untreated and irradiated choroidal melanomas with color Doppler imaging (CDI), a noninvasive method providing quantitative measures of blood flow, to determine if the tumor vessel damage associated with irradiation can be detected using this technology. CDI was performed on 122 untreated and 76 previously irradiated tumors using a Q2000 color Doppler ultrasound unit. Spectral analysis was performed on all detectable vascular regions within the tumor to obtain estimates of the peak systolic and end diastolic flow velocities and resistive index ((syst-diast)/syst). Vessels were detected in 93% of the untreated tumors and in 63% of the treated tumors (p<0.001, X2), and the median number of vascular regions found was higher among untreated tumors (3 vs 1, p=0.001, Wilcoxon Rank Sum). The effect of treatment status on the detection of tumor vessels was significant (p=0.039), controlling for age, sex, largest tumor pretreatment diameter, and tumor height at CDI in a logistic regression model. Mean resistive index was lower in the untreated tumors (0.53 vs 0.58, p=0.0050), controlling for tumor height and other covariates in an analysis of variance. On examination with CDI, irradiated tumors had fewer detectable vascular regions and greater resistance to flow than untreated tumors, a pattern consistent with known radiation effects.
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10.1177/112067210101100208
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8033946
|
Wernicke's encephalopathy induced by hyperemesis gravidarum, associated with bilateral caudate lesions on computed tomography and magnetic resonance imaging.
|
The case of an 18-year-old woman with Wernicke's encephalopathy induced by hyperemesis gravidarum is reported. She had severe vomiting and received antiemetic therapy and intravenous administration of glucose and low-dose insulin solution without thiamine. She developed coma, nystagmus, ataxia and polyneuropathy. CT and MR imaging showed bilateral caudate lesions as well as symmetrical periventricular lesions of the thalamus and hypothalamus and periaqueductal gray matter. Caudate lesions are quite rare in Wernicke's encephalopathy.
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10.1159/000117034
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11310206
|
The effect of an osteolytic tumor on the three-dimensional trabecular bone morphology in an animal model.
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To investigate the application of micro-computed tomography (microCT) for the assessment of density differences and deterioration of three-dimensional architecture of trabecular bone in an experimental rat model for tumor-induced osteolytic defects. Walker carcinosarcoma 256 malignant breast cancer cells (W256) were surgically implanted into the medullary canal of the left femur of 15 4-month-old rats. Twenty-eight days after surgery all animals were killed and both femora from each rat were harvested. A total of 30 specimens (left and right femur) were scanned in a desktop microCT imaging system (microCT 20, Scanco Medical) to assess densitometric and architectural parameters. For each specimen a total of 200 micro-tomographic slices with a resolution of 30 microns in the distal metaphysis was taken. Bone mineral content (BMC) was analyzed for both cortical and trabecular bone (ctBMC), and for trabecular bone only (tBMC). Architectural indices (BV/TV, Tb. N, Tb. Th, Tb. Sp) according to standard definitions used in histomorphometry were calculated for trabecular bone. The quantitative analysis of density parameters revealed significantly (P < 0.001) lower values for ctBMC and tBMC in the tumor-bearing group (T) of 26% and 31%, respectively, compared with the contralateral control group. The quantitative analysis revealed significant (P < 0.001) changes in the architectural parameters in the tumor-bearing bones compared with the contralateral control group: BV/TV was 30% lower, Tb. N and BS/TV decreased by 24% and 21%, respectively, Tb. Th. decreased by 10% and Tb. Sp. increased by 94%. This study demonstrates that microCT is able to provide three-dimensional parameters of bone mass and trabecular structure in an animal model for tumor-induced bone loss. Recent advances in therapeutic approaches for skeletal diseases such as osteoporosis and metastatic bone diseasse rely on an understanding of the effects of the agents on the mechanical properties of bone. In order to quantify the structural changes of the affected bones the application of a non-destructive method is mandatory. The use of microCT seems to be a great advantage, since biomechanical tests and further histologic analysis can be done for the same specimens.
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10.1007/s002560000287
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25627305
|
[Legionella pneumonia after infliximab in a patient with rheumatoid arthritis].
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The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
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10.1016/j.rbr.2013.04.008
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37074245
|
Accuracy of 3-dimensional-printed customized transfer tray using a flash-free adhesive system in digital indirect bonding: An in vivo study.
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This paper evaluated the accuracy of a computer-aided design and manufacturing indirect bonding technique using a new customized 3D-printed transfer tray and a flash-free adhesive system for orthodontic bonding. This in vivo study analyzed 106 teeth selected from 9 patients undergoing orthodontic treatment. Quantitative deviation analysis was performed to evaluate the bonding positioning errors, assessing the differences between the virtually planned and the clinically transferred bracket position after indirect bonding procedures by superimposing 3-dimensional dental scans. Estimated marginal means were evaluated for individual brackets and tubes, arch sectors, and overall collected measurements. A total of 86 brackets and 20 buccal tubes were analyzed. Among individual teeth, mandibular second molars showed the highest positioning errors, whereas maxillary incisors reported the lowest values. Considering arch sectors, the posterior areas showed greater displacements than the anterior areas, as the right side compared to the left side, with a higher error rate reported for the mandibular arch than the maxillary arch. The overall bonding inaccuracy measurement was 0.35 mm, below the clinical acceptability limit of 0.50 mm. The accuracy of a 3-dimensional-printed customized transfer tray using a flash-free adhesive system in computer-aided design and manufacturing indirect bonding was generally high, with greater positioning errors for posterior teeth. Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.
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10.1016/j.ajodo.2023.02.017
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37150105
|
In vitro and in vivo antimicrobial activity of self-assembled melittin nanoparticles: A comparative study with melittin peptide.
|
The aim of the present study was to analyse the efficacy of self-assembled melittin nanoparticles (MelNP) and compare with native melittin peptide (Mel). Self-assembly formation of the melittin was promoted by heating at 90 °C for 50 min followed by cooling at room temperature. SEM micrographs revealed the formation of nanovesicles. MIC of MelNP against E. coli, S. aureus and P. aeruginosa was found to be 4, 2, and 2 μM, respectively while it was 8, 8 and 4 μM for Mel peptide. Markedly, MelNP showed 12.6 % hemolysis at 8 μM whereas with Mel it was about 71.63 %. The lytic activity of MelNP was also higher in the presence of trypsin/serum than Mel. Both MelNP and Mel exhibited membranolytic activity with cellular disintegration. Further, toxicity analysis studied up to 72 h showed that MelNP was non-toxic to zebrafish embryos up to 6 μM; however, with Mel exposed embryos showed up 30 dead embryos. Bacterial load was markedly reduced in MelNP and Mel exposed infected embryos than compared to the infected one. Moreover, the peptides were also responsible for reducing the infection and prolonging the survivability in infected embryos. Thus, MelNP could be considered an efficient and safer therapeutic molecule that Mel and wherein further experiments are warranted to affirm the broad spectrum efficiency. Copyright © 2023 Elsevier B. V. All rights reserved.
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10.1016/j.colsurfb.2023.113331
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26432890
|
Cutting Edge: Inhibiting TBK1 by Compound II Ameliorates Autoimmune Disease in Mice.
|
TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that plays a crucial role in innate immunity. Enhanced TBK1 function is associated with autoimmune diseases and cancer, implicating the potential benefit of therapeutically targeting TBK1. In this article, we examined a recently identified TBK1 inhibitor Compound II on treating autoimmune diseases. We found that Compound II is a potent and specific inhibitor of TBK1-mediated IFN response. Compound II inhibited polyinosinic-polycytidylic acid-induced immune activation in vitro and in vivo. Compound II treatment also ameliorated autoimmune disease phenotypes of Trex1(-/-) mice, increased mouse survival, and dampened the IFN gene signature in TREX1 mutant patient lymphoblasts. In addition, we found that TBK1 gene expression is elevated in systemic lupus erythematosus patient cells, and systemic lupus erythematosus cells with high IFN signature responded well to Compound II treatment. Together, our findings provided critical experimental evidence for inhibiting TBK1 with Compound II as an effective treatment for TREX1-associated autoimmune diseases and potentially other interferonopathies. Copyright © 2015 by The American Association of Immunologists, Inc.
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10.4049/jimmunol.1500162
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17106807
|
Soil fungal communities underneath willow canopies on a primary successional glacier forefront: rDNA sequence results can be affected by primer selection and chimeric data.
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Soil fungal communities underneath willow canopies that had established on the forefront of a receding glacier were analyzed by cloning the polymerase chain reaction (PCR)-amplified partial small subunit (18S) of the ribosomal (rRNA) genes. Congruence between two sets of fungus-specific primers targeting the same gene region was analyzed by comparisons of inferred neighbor-joining topologies. The importance of chimeric sequences was evaluated by Chimera Check (Ribosomal Database Project) and by data reanalyses after omission of potentially chimeric regions at the 5'- and 3'-ends of the cloned amplicons. Diverse communities of fungi representing Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota were detected. Ectomycorrhizal fungi comprised a major component in the early plant communities in primary successional ecosystems, as both primer sets frequently detected basidiomycetes (Russulaceae and Thelephoraceae) forming mycorrhizal symbioses. Various ascomycetes (Ophiostomatales, Pezizales, and Sordariales) of uncertain function dominated the clone libraries amplified from the willow canopy soil with one set of primers, whereas the clone libraries of the amplicons generated with the second primer set were dominated by basidiomycetes. Accordingly, primer bias is an important factor in fungal community analyses using DNA extracted from environmental samples. A large proportion (>30%) of the cloned sequences were concluded to be chimeric based on their changing positions in inferred phylogenies after omission of possibly chimeric data. Many chimeric sequences were positioned basal to existing classes of fungi, suggesting that PCR artifacts may cause frequent discovery of new, higher level taxa (order, class) in direct PCR analyses. Longer extension times during the PCR amplification and a smaller number of PCR cycles are necessary precautions to allow collection of reliable environmental sequence data.
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10.1007/s00248-004-0006-x
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6018511
|
Information delivery and the sensory evoked potential.
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The waveform of evoked responses recorded from human scalp is not determined solely by the physical eliciting stimulus, but also varies as a function of the effective information provided by the stimulus. There is a positive component whose latency is determined by the point in time at which ambiguity is reduced, and whose shape and amplitude are influenced by whether it is the presence or absence of an external event which delivers the information.
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10.1126/science.155.3768.1436
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21858763
|
From the discovery of vascular endothelial growth factor to the introduction of avastin in clinical trials - an interview with Napoleone Ferrara by Domenico Ribatti.
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Napoleone Ferrara and his colleagues at Genentech were the first to isolate and clone vascular endothelial growth factor (VEGF) in 1989. His laboratory has investigated many aspects of VEGF biochemistry and molecular biology. In 1993, Ferrara reported that inhibition of VEGF-induced angiogenesis by specific monoclonal antibodies resulted in dramatic suppression of the growth of a variety of tumors in vivo. These findings provided an important evidence that inhibition of angiogenesis may suppress tumor growth and blocking VEGF action could have therapeutic value for a variety of malignancies. A further development was the design in a rational fashion in 1997 of a humanized anti-VEGF monoclonal antibody (Avastin), now in clinical trials as a treatment for several solid tumors and also outside of cancer, in the treatment of age-related macular degeneration (AMD). Ferrara's work is revolutionizing quality of life for many of the estimated 1.2 million individuals in the US who have wet AMD. Upwards of a million AMD patients worldwide have already received anti-VEGF antibody therapy.
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10.1387/ijdb.103216dr
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33805367
|
Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.
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In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e. g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i. e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).
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10.3390/cancers13071565
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30993381
|
In vitro models to study insulin and glucocorticoids modulation of trimethyltin (TMT)-induced neuroinflammation and neurodegeneration, and in vivo validation in db/db mice.
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Brain susceptibility to a neurotoxic insult may be increased in a compromised health status, such as metabolic syndrome. Both metabolic syndrome and exposure to trimethyltin (TMT) are known to promote neurodegeneration. In combination the two factors may elicit additive or compensatory/regulatory mechanisms. Combined effects of TMT exposure (0.5-1 μM) and mimicked metabolic syndrome-through modulation of insulin and glucocorticoid (GC) levels-were investigated in three models: tridimensional rat brain cell cultures for neuron-glia effects; murine microglial cell line BV-2 for a mechanistic analysis of microglial reactivity; and db/db mice as an in vivo model of metabolic syndrome. In 3D cultures, low insulin condition significantly exacerbated TMT's effect on GABAergic neurons and promoted TMT-induced neuroinflammation, with increased expression of cytokines and of the regulator of intracellular GC activity, 11β-hydroxysteroid dehydrogenase 1 (11β-Hsd1). Microglial reactivity increased upon TMT exposure in medium combining low insulin and high GC. These results were corroborated in BV-2 microglial cells where lack of insulin exacerbated the TMT-induced increase in 11β-Hsd1 expression. Furthermore, TMT-induced microglial reactivity seems to depend on mineralocorticoid receptor activation. In diabetic BKS db mice, a discrete exacerbation of TMT neurotoxic effects on GABAergic neurons was observed, together with an increase of interleukin-6 (IL-6) and of basal 11β-Hsd1 expression as compared to controls. These results suggest only minor additive effects of the two brain insults, neurotoxicant TMT exposure and metabolic syndrome conditions, where 11β-Hsd1 appears to play a key role in the regulation of neuroinflammation and of its protective or neurodegenerative consequences.
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10.1007/s00204-019-02455-0
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11928669
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[Occupational exposure to chemicals in the manufacture of rubber tires].
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The work environment of the rubber industry company, producing various types of tires, was assessed and the workers of the plant were included in a cohort study of mortality. Concentrations of twenty chemical substances at 137 workposts were measured by employees of the plant laboratory and the sanitary and epidemiological station in 1981-1996. The mean values and concentration ranges were determined by departments and workposts. The excess of threshold limit values was analyzed. The workposts with exposure to agents possibly carcinogenic to humans were identified. The analysis performed will render it possible to calculate doses of cumulative exposure to given compounds among workers covered by the epidemiological study.
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987076
|
Regulation of female sexual behavior in the golden hamster: behavioral effects of mating and ovarian hormones.
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In the female hamster, sexual receptivity was abbreviated following copulation. Short-term effects of mating, lasting approximately 24-48 hr, were observed in females mated in either estradiol- or estradiol-and-progesterone-induced estrus. Long-term effects of copulation, of 9 days or more in duration, were apparent only in females chronically treated with both estradiol and progesterone, suggesting that progesterone exposure prolongs the inhibitory effects of mating. When progesterone stimulation was intermittent through the use of short-acting injection procedures, recovery from mating could be detected in 48 hr and was complete within 96 hr after copulation. The pattern of behavioral response to ovarian hormones in unmated females was also documented, replicating the "biphasic" effect of progesterone in this species. The inhibitory effects of mating and progesterone summate to produce consistent decrements in female sexual receptivity. It is postulated that short-term postcopulatory abbreviations in receptivity would reduce the vulnerability of the estrous female while long-term inhibitions, interacting with sustained progesterone stimulation, would reduce the probability of mating during pregnancy when hormone levels are elevated for a prolonged period.
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10.1037/h0077274
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19534665
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Natural killer cell receptors in human immunodeficiency virus infection: pathways to protection or doors to disappointment?
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In the absence of effective treatment, infection with the human immunodeficiency virus (HIV) ultimately leads to the acquired immune deficiency syndrome (AIDS). Many attempts have been made to prevent and attenuate HIV infection. While antiretroviral therapies for infected individuals have had great success, preventative and therapeutic vaccines focused on both humoral and cellular-mediated immunity have failed. Recently, several natural killer cell receptor (NKR) genotypes, in concert with certain class I human histompatibility-linked antigens (HLA) were found to be associated with protection from HIV infection and/or disease progression. These receptors are expressed on both natural killer (NK) cells and subsets of T lymphocytes. As HIV infection is often associated with attenuation of NK cells and much remains unknown about the basic functions of NKR, it remains undetermined whether the protective effect of these receptors relates to their expression on NK cells, T lymphocytes or both. This review summarizes current literature regarding NKR and HIV infection, and addresses several major questions remaining about the role of these receptors in protection against infection and disease progression.
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10.2174/157016209789346273
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32251560
|
[Laparoscopic orchiopexy for inguinal palpable cryptorchidism].
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To investigate the feasibility and advantages of laparoscopic orchiopexy in the treatment of inguinal palpable cryptorchidism. This study included 773 cases of inguinal palpable cryptorchidism with 869 undescended testes, 218 on the left, 459 on the right and 96 bilaterally. The patients were aged 6 months to 8 years, averaging 20 months. The surgical procedures involved cutting open the posterior peritoneal wall with the ultrasonic scalpel, dissecting the spermatic cord close to the inferior pole of the kidney, separating the posterior peritoneum from the vas deferens, severing the testicular gubernaculum, pulling the testis back into the abdominal cavity and, with the vas deferens protected, bringing the testis down into the scrotum and getting it fixed. All the operations were successfully performed, with an average operation time of 34.8 ± 5.4 minutes and no conversion to open surgery. Ipsilateral patent processus vaginalis was found in 692 (89.5%) of the 773 cases, and contralateral concealed hernia in 233 (34.4%) of the 677 cases of unilateral cryptorchidism, which were all treated by high ligation of the hernial sac. There was no subcutaneous emphysema intraoperatively or vomiting, abdominal distension, wound bleeding and obvious pain postoperatively. The patients were followed up for 6 to 18 months, during which, regular Doppler ultrasonography revealed that the testes were located in the scrotum with no testicular retraction and atrophy, inguinal hernia or hydrocele. Laparoscopic orchiopexy is safe and effective for the treatment of inguinal palpable cryptorchidism, and meanwhile can be used for the detection and management of contralateral concealed hernia and the prevention of metachronous inguinal hernia.
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18266332
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An organic/Si nanowire hybrid field configurable transistor.
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We report a field configurable transistor (FCT) fabricated on a Si nanowire FET platform by integrating a thin film of conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV) and an ionic conductive layer (RbAg4I5) into the gate. The FCT can be precisely configured to desired nonvolatile analog state dynamically, repeatedly, and reversibly by controlling the concentration of iodide ions in the MEH-PPV layer with a gate voltage. The flexible configurability and plasticity of the FCT could facilitate field-programmable circuits for defect-tolerance and synapse-like devices for learning.
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10.1021/nl073112y
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8135784
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Characterization of NF(P), the nuclear factor that interacts with the regulatory P sequence (5'-CGAAAATTTCC-3') of the human interleukin-4 gene: relationship to NF-kappa B and NF-AT.
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The P sequence of the human interleukin-4 (IL-4) gene, which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore (A23187) in Jurkat T cells, shares sequence similarity with the NF-kappa B and the NF-AT binding sites. We examined whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and NF-AT. NF-kappa B (P65 or P65/P50 heterodimer) bound to the P sequence in electrophoretic mobility shift assays (EMSA) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T cells. In EMSAs, NF(P) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence. Both mobility shift and sequence specificity of NF-AT were similar to those of NF(P) and only a small amount of P65 was detected in NF(P) in crude nuclear extracts. These results indicate that the component(s) of NF-AT has the potential to reconstitute NF(P) whereas NF-kappa B alone cannot account for NF(P) in crude extracts. Unlike NF-AT, NF(P) does not contain AP1 as its DNA binding component.
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10.1006/bbrc.1994.1248
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33233149
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Conidial heat resistance of various strains of the food spoilage fungus Paecilomyces variotii correlates with mean spore size, spore shape and size distribution.
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Contamination by spores is often the cause of fungal food spoilage. Some distinct strains of the food spoilage fungus Paecilomyces variotii are able to produce airborne conidia that are more heat-resistant than similar species. These ellipsoid asexual spores can vary in size between strains, but also within strains. Here, we compared four measurement techniques to measure conidia size and distribution of five heat-sensitive and five heat-resistant P. variotii strains. Light microscopy (LM), Scanning Electron Microscopy (SEM) and Coulter Counter (CC) were used to measure and compare the spherical equivalent diameter, while CC and flow cytometry were used to study spore size distributions. The flow cytometry data was useful to study spore size distributions, but only relative spore sizes were obtained. There was no statistic difference between the method used of spore size measurement between LM, SEM and CC, but spore size was significantly different between strains with a 2.4-fold volume difference between the extremes. Various size distribution and shape parameters were correlated with conidial heat resistance. We found significant correlations in mean spore size, aspect ratio, roundness and skewness in relation to heat resistance, which suggests that these parameters are indicative for the conidial heat resistance of a P. variotii strain. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
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10.1016/j.foodres.2020.109514
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38825766
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Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study.
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To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE. These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia-Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire-Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS). A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i. e., adults), and PWH 15 were <18 years (i. e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were "leisure time" (58% showed maladjustment) and "work/studies" (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of "sport" (49.4 [28.6]), "physical health" (40.5 [25.8]) and "future" (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in "lying/sitting/kneeling/standing," "function of legs" and "leisure activities and sports," with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression. PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression. © 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.
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10.1111/hae.15057
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35725651
|
Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate.
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Muscle atrophy is an increasingly global health problem affecting millions, there is a lack of clinical drugs or effective therapy. Excessive loss of muscle mass is the typical characteristic of muscle atrophy, manifesting as muscle weakness accompanied by impaired metabolism of protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one of the main components of the ketone body, has been reported to be effective for the obvious hemodynamic effects in atrophic cardiomyocytes and exerts beneficial metabolic reprogramming effects in healthy muscle. This study aims to exploit how the 3HB exerts therapeutic effects for treating muscle atrophy induced by hindlimb unloaded mice. Anabolism/catabolism balance of muscle protein was maintained with 3HB via the Akt/FoxO3a and the mTOR/4E-BP1 pathways; protein homeostasis of 3HB regulation includes pathways of ubiquitin-proteasomal, autophagic-lysosomal, responses of unfolded-proteins, heat shock and anti-oxidation. Metabolomic analysis revealed the effect of 3HB decreased purine degradation and reduced the uric acid in atrophied muscles; enhanced utilization from glutamine to glutamate also provides evidence for the promotion of 3HB during the synthesis of proteins and nucleotides. 3HB significantly inhibits the loss of muscle weights, myofiber sizes and myofiber diameters in hindlimb unloaded mouse model; it facilitates positive balance of proteins and nucleotides with enhanced accumulation of glutamate and decreased uric acid in wasting muscles, revealing effectiveness for treating muscle atrophy. © 2022. The Author(s).
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10.1186/s13578-022-00826-2
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35765994
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Left pulmonary veins draining into persistent left superior caval vein in presence of unroofed coronary sinus.
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We report a case of 5-year-old girl with double outlet right ventricle with a rare combination of partial anomalous pulmonary venous drainage into a persistent left superior caval vein in the presence of an unroofed coronary sinus while highlighting its possible embryological origins and therapeutic implications. © 2022 Wiley Periodicals LLC.
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10.1111/jocs.16733
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10926041
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Integrating prevention education into the medical school curriculum: the role of departments of family medicine.
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Departments of family medicine--including departments of family and community medicine, departments of family and preventive medicine, and departments of family practice-at U. S. medical schools regularly participate in teaching prevention principles to students, using a variety of formats and methods. Required clinical experiences (i. e., clerkships and preceptorships), required nonclinical courses, and electives frequently include prevention content. Collaborative interdisciplinary clerkships, interdisciplinary nonclinical courses, and courses directed by other departments also enable family medicine faculty to teach prevention principles. This article describes examples of innovative educational programs in which family medicine faculty teach prevention content to medical students. Directions for future educational efforts by family medicine faculty in the prevention area are proposed.
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10.1097/00001888-200007001-00008
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11672584
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Urokinase-type plasminogen activator up-regulates its own expression by endothelial cells and monocytes via the u-PAR pathway.
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Signal transduction by urokinase-type plasminogen activator (u-PA) bound to its cell receptor has been well established. In the present study, we found, for the first time to our knowledge, that u-PA promotes its own synthesis by endothelial cells and monocytes. This phenomenon was characterized and shown to involve the u-PA receptor (u-PAR) pathway. The finding may be of general importance, since most cells that express u-PAR also produce u-PA. Human umbilical vein endothelial cells (HUVECs), U937 monocytes, and human peripheral blood monocytes (PFMCs) were incubated with diisopropylfluorophosphate (DFP)-pretreated u-PA, the amino-terminal fragment (ATF) of u-PA, or the kringle domain. A threefold up-regulation of u-PA secretion and synthesis by u-PA or ATF was found. The predominant effect was expressed in HUVECs, in which u-PA mRNA was also up-regulated. The u-PA kringle domain had no effect on u-PA synthesis, leading to the conclusion that the EGF domain was responsible. This was also consistent with the additional finding that the u-PAR, to which the EGF domain binds, was necessary for the up-regulation. The results indicate that u-PA up-regulates itself via its EGF domain and u-PAR. The possibilities that the results were related to displacement of receptor-bound u-PA or the blocking of u-PA incorporation into the cells were excluded. A modest up-regulation of u-PAR was also associated with this phenomenon.
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10.1016/s0049-3848(01)00322-x
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11359151
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Homologous collagen substances for vocal fold augmentation.
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Dysphonia resulting from failure of glottic closure during voicing is a difficult clinical problem. Recently developed homologous collagen compounds may be beneficial in treating this problem. The objectives of this thesis are to: 1) evaluate the potential site(s) of collagen graft placement in the human vocal fold, quantify the amount of graft material that can be injected into these sites, and determine how these sites are accessed by the currently available surgical tools for injection; 2) determine the effects of the superficial vocal fold implant on laryngeal vibratory patterns and characterize how the implant affects the forces required to bring vocal folds into an adducted position for vibration; and 3) evaluate the host response to two different forms of cadaveric collagen. Prospective laboratory. Three separate experiments were undertaken: 1) Eight cadaver larynges were injected with collagen compounds through a 27-gauge needle. The amount of substance required to medialize the vocal fold and potential positions for graft placement were evaluated. 2) Six cadaver larynges were mounted on a stabilizing stand while airflow, vocal fold length, adduction forces, and abduction forces on the vocal folds were manipulated. Vibratory patterns before and after the injection of the vocal folds with solubilized collagen were assessed. 3) A nude mouse model was used to study the host response to two different exogenous collagen compounds. Solubilized collagen compounds could be injected reliably into the superficial layer of the lamina propria (SLLP), medial portion of the thyroarytenoid muscle, or lateral portion of the thyroarytenoid muscle. When injected superficially, significantly less material was required to displace the medial edge of the vocal fold to midline (P =.0001). When graft material was placed into the medial portion of the thyroarytenoid (TA) muscle, the forces required to bring the vocal fold into a position suitable for vibration were significantly reduced (P =.0106) and the vibratory patterns of the vocal folds were not impaired. Both AlloDerm(R) and Dermalogen(R) solubilized preparations of human dermal tissue were well tolerated in the nude-mouse model. Minimal inflammatory reaction occurred. Small amounts of graft material were identified histologically at the end of the 6-month study period. The graft material appeared organized and had been infiltrated with fibroblasts of host origin. Homologous collagen compounds can be reliably injected into the cadaveric human larynx. When the substances are injected into the medial portion of the TA muscle, immediately deep to the vocal ligament, they decrease the force of contraction needed to bring the vocal folds into a position adequate for phonation and have minimal affect on the vibratory patterns. These forms of homologous collagen are well tolerated. A small amount persists over a 6-month interval. These materials warrant further clinical trials in human subjects.
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10.1097/00005537-200105000-00001
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7262172
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Control of antibiotic therapy in paediatric patients. II. Appropriateness of antibiotic choice in selected diseases.
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The adequacy of antibiotic choice and the importance of the physician's knowledge of antibiotic use in causing errors in prescribing were investigated. A prospective three-month study was conducted in nine Italian pediatric hospital wards, involving every patient admitted to hospital for otitis, pneumonia or pharyngotonsillitis. The suspected aetiology and the antibiotic prescribed were recorded on a special form by the physician in charge. Each choice of antimicrobial agent was judged as adequate, justifiable or not justified. Out of 314 prescriptions 56.1% were assessed as adequate, 4.1% as justifiable and 39.8% as not justified. Analysis of the suspected bacteria, and of the correlation between the presumed aetiological agent and the prescribed antibiotic, demonstrates that inadequate knowledge of the physician plays a major role in producing a high percentage of unjustified prescriptions.
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10.1007/BF00607147
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36477738
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The cribriform morphology impairs Gleason 7 prostate cancer lesion detection on multiparametric magnetic resonance imaging.
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Prostate multiparametric magnetic resonance imaging (mpMRI) is a useful tool for the detection of tumor lesions however, some clinically significant lesions are still missed. We determined whether the cribriform pattern has an effect on lesion detection in mpMRI. We reviewed the single-institution database of the patients who underwent mpMRI before radical prostatectomy. We included the patients only with the Gleason 7 final pathology of open radical prostatectomy with curative intent between 2016 and 2021. Prostatectomy mappings according to the 16-sector map and cribriform patterns were re-evaluated by two genitourinary pathologists. Prostate mpMRIs were read by two genitourinary radiologists. If the index and nonindex lesions in pathology mapping were matched with mpMRI as Prostate Imaging Reporting and Data System-3 or higher, it was defined as detectable. We compared the detection rates of lesions with and without cribriform morphology. In regression analysis, we also assessed the factors affecting the detectability of prostate cancer lesions. A total of 120 patients and 157 lesions were included in our study. While 52 of 83 cribriform pattern positive lesions could be detected in mpMRI, 59 of 74 cribriform pattern negative lesions could be detected (62.7% vs. 79.7%, respectively, p = 0.019). The lesions were also distributed homogeneously according to diameters and analyzed separately. All lesions between 21 and 30 mm with the negative cribriform pattern were detected on mpMRI. However, only 77.8% of cribriform pattern positive lesions between 21 and 30 mm could be detected (p = 0.034). The Higher D'Amico risk group and the absence of cribriform morphology were independent predictors for the lesion detection on mpMRI. The presence of cribriform pattern in Gleason 7 prostate cancer lesions decreases the lesion detection rate of mpMRI. © 2022 Wiley Periodicals LLC.
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10.1002/pros.24465
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9656453
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Oxidised mannan antigen conjugates preferentially stimulate T1 type immune responses.
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It is desirable to be able to produce either T1 or T2 responses and we have found that, in mice, mannose--coupled antigens stimulated T2 type responses antibodies and CTLs, whereas if oxidized, mannose--coupled antigens stimulated T1 responses little antibody and a potent CTL response. In addition, the cytokine profiles support the T1rT2 differentiation with these immunizations, in that oxidized mannan antigen gives IFNg, IL-2 and IL-12 production, whereas in the absence of oxidization, IL-4 and not the other cytokines is produced. A number of antigens have been examined--particularly Mucin 1 and the delivery method using mannose may be applicable to the other antigens.
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10.1016/s0165-2427(98)00094-4
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22256957
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The "Miserable Minority" following mild traumatic brain injury: who are they and do meta-analyses hide them?
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Ruff et al. (1994; Ruff, Camenzuli, & Mueller, 1996) hypothesized that some mild traumatic brain injury (MTBI) patients will suffer chronic symptomatic complaints and impairments, identifying this subgroup as the "miserable minority." However, several meta-analyses of the effects of MTBI have been published (e. g., Rohling et al., 2011) showing no significant cognitive impairments following recovery. Recently Pertab, James, and Bigler (2009) suggested that meta-analysis might be obscuring impairments in some MTBI patients, presenting a hypothetical score distribution to illustrate their claim. Our statistical analyses of their hypothetical figure and of several other potential distributions containing an impaired subgroup that varied as a function of effect size and base rate of occurrence did not support the existence of a miserable minority that is obscured in meta-analyses by the larger group of MTBI patients experiencing full recovery. Indeed, given our recent published MTBI effect size of -0.07 (Rohling et al., 2011), for an impaired subgroup to exist, the level of impairment would have to be just under a tenth of a standard deviation, equivalent to a WMS-IV Index score value of 1 point. At effect sizes this small, any cut score chosen on a test to diagnose patients would result in more false positives than true positives. This greatly increases the risk of misdiagnosis in persons who are susceptible to misattribution, expectancy effects, and "diagnosis threat," thereby increasing the risk of iatrogenic illness.
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10.1080/13854046.2011.647085
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1614380
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Public and private responsibility for financing nursing-home care: the effect of Medicaid asset spend-down.
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Data from a nationally representative sample of nursing-home residents at the beginning of 1987 are used to assess the interaction of Medicaid asset spend-down, the distribution of nursing-home days by payment source, and the effect of proposed changes in public financing of nursing-home care. Three out of five nursing-home residents were covered by Medicaid in January 1987; nearly all of the remainder were private-pay. Most Medicaid recipients were covered by Medicaid when they entered the care facility at the start of an episode, but 18 percent had spent down and were originally admitted as private-pay. A universal nursing-home benefit that insured the first six months of each nursing-home episode would cover 16 percent of the people in nursing homes on a given day, disproportionately those who are private-pay. A universal benefit with a 24-month waiting period would cover 56 percent of nursing-home residents on a given day, and would tend to favor those financed by Medicaid.
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17085827
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The burden of cardiovascular disease in the Indian subcontinent.
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Ischaemic heart disease and stroke are among the most common causes of death and disability in the world. The Indian subcontinent (including India, Pakistan, Bangladesh, Sri Lanka, and Nepal) has among the highest rates of cardiovascular disease (CVD) globally. Previous reports have highlighted the high CVD rates among South Asian immigrants living in Western countries, but the enormous CVD burden within the Indian subcontinent itself has been underemphasized. In this review, we discuss the existing data on the prevalence of CVD and its risk factors in the Indian subcontinent. We also review recent evidence indicating that the burden of coronary heart disease in the Indian subcontinent is largely explained on the basis of traditional risk factors, which challenges the common thinking that South Asian ethnicity per se is a strong independent risk factor for coronary heart disease. Finally, we suggest measures to implement in policy, capacity building, and research to address the CVD epidemic in the Indian subcontinent.
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37056891
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Comparative Study of Intraoperative Fluorescein and Indocyanine Green Videoangiography for Ruptured Cerebral Aneurysms Clipping: A Single Centre Study of 30 Cases.
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Aim This study assesses the application of microscope integrated videoangiography techniques in aneurysm clipping surgery using Indocyanine Green and Fluorescein fluorophores and evaluates merits and demerits of each technique. Materials and Methods Total 30 patients of cerebral aneurysmal clipping were included. Standard microsurgical procedures were done. After clipping, we administered a 25 mg bolus intravenous dose of indocyanine green with microscope focused through the INFRARED 800 camera module, followed by administration of 60 mg bolus intravenous dose of fluorescein with microscope focused through the yellow 560 module and images were assessed. Results The average aneurysm size was 17 mm. In 12 patients (40%), FL-VA allowed better assessment of perforating arteries (seven cases) or distal branches (three cases) or both (two cases), when compared with ICG-VA. In one case of MCA (M1) aneurysm, ICG-VA showed no fluorescent signal in one of the distal trunks whereas FL-VA showed normal signal. In one case of ACOM aneurysm, perforators were missed on ICG-VA but were seen on FL-VA. FL-VA was able to identify inadequate aneurysm clipping in one case. In two patients, FL-VA provided the advantage of real-time manipulation of the vessels to expose the vessels and aneurysms of interest. Fluorescein detected all the perforators that were visible under white light (68/68) whereas ICG was able to detect 56 (82.35%) perforators ( p -value< 0.05). Conclusion Intraoperative ICG and Fluorescein videoangiography recognize inadequate occlusion of aneurysm, decreased flow in branches or perforators. When various study parameters were considered such as ability to assess small size perforators, branching vessels, adequacy of aneurysmal clipping, and useful information on repeat imaging, FL-VA was found superior to ICG-VA. Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons. org/licenses/by-nc-nd/4.0/ ).
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10.1055/s-0042-1751006
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19760493
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A classification and meta-analysis of community-based directly observed therapy programs for tuberculosis treatment in developing countries.
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In many developing countries, Directly Observed Therapy (DOT) for tuberculosis has been undertaken mainly in the clinic setting. However, clinic-based DOT may create a high patient load in already overburdened health facilities and increase barriers to care by requiring patients to travel to clinic frequently for therapy. Community-based DOT (CBDOT) may overcome some of these problems. This aims of this review are (a) to describe the main features of CBDOT programs, and (b) to compare features and outcomes of CBDOT programs that do and do not offer financial reward for CBDOT providers. Ten major features define CBDOT program structure and function. Programs that paid their CBDOT providers tended to differ from unpaid programs based on all of these features. CBDOT programs in which providers received financial reward had success rates of 85.7 versus 77.6% in programs without financial reward for providers. This difference was not statistically significant. CBDOT programs fall into two major archetypes, which differ in their structure and possibly in their outcomes.
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10.1007/s10900-009-9174-4
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33742770
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A retrospective analysis of actionable pharmacogenetic/genomic biomarker language in FDA labels.
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The primary goal of precision medicine is to maximize the benefit-risk relationships for individual patients by delivering the right drug to the right patients at the right dose. To achieve this goal, it has become increasingly important to assess gene-drug interactions (GDIs) in clinical settings. The US Food and Drug Administration (FDA) periodically updates the table of pharmacogenetic/genomic (PGx) biomarkers in drug labeling on their website. As described herein, an effort was made to categorize various PGx biomarkers covered by the FDA-PGx table into certain groups. There were 2 major groups, oncology molecular targets (OMT) and drug-metabolizing enzymes and transporters (DMETs), which constitute ~70% of all biomarkers (~33% and ~35%, respectively). These biomarkers were further classified whether their labeling languages could be actionable in clinical practice. For OMT biomarkers, ~70% of biomarkers are considered actionable in clinical practice as they are critical for the selection of appropriate drugs to individual patients. In contrast, ~30% of DMET biomarkers are considered actionable for the dose adjustments or alternative therapies in specific populations, such as CYP2C19 and CYP2D6 poor metabolizers. In addition, the GDI results related to some of the other OMT and DMET biomarkers are considered to provide valuable information to clinicians. However, clinical GDI results on the other DMET biomarkers can possibly be used more effectively for dose recommendation. As the labels of some drugs already recommend the precise doses in specific populations, it will be desirable to have clear language for dose recommendation of other (or new) drugs if appropriate. © 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
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10.1111/cts.13000
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20157009
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Imaging memory in temporal lobe epilepsy: predicting the effects of temporal lobe resection.
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Functional magnetic resonance imaging can demonstrate the functional anatomy of cognitive processes. In patients with refractory temporal lobe epilepsy, evaluation of preoperative verbal and visual memory function is important as anterior temporal lobe resections may result in material specific memory impairment, typically verbal memory decline following left and visual memory decline after right anterior temporal lobe resection. This study aimed to investigate reorganization of memory functions in temporal lobe epilepsy and to determine whether preoperative memory functional magnetic resonance imaging may predict memory changes following anterior temporal lobe resection. We studied 72 patients with unilateral medial temporal lobe epilepsy (41 left) and 20 healthy controls. A functional magnetic resonance imaging memory encoding paradigm for pictures, words and faces was used testing verbal and visual memory in a single scanning session on a 3T magnetic resonance imaging scanner. Fifty-four patients subsequently underwent left (29) or right (25) anterior temporal lobe resection. Verbal and design learning were assessed before and 4 months after surgery. Event-related functional magnetic resonance imaging analysis revealed that in left temporal lobe epilepsy, greater left hippocampal activation for word encoding correlated with better verbal memory. In right temporal lobe epilepsy, greater right hippocampal activation for face encoding correlated with better visual memory. In left temporal lobe epilepsy, greater left than right anterior hippocampal activation on word encoding correlated with greater verbal memory decline after left anterior temporal lobe resection, while greater left than right posterior hippocampal activation correlated with better postoperative verbal memory outcome. In right temporal lobe epilepsy, greater right than left anterior hippocampal functional magnetic resonance imaging activation on face encoding predicted greater visual memory decline after right anterior temporal lobe resection, while greater right than left posterior hippocampal activation correlated with better visual memory outcome. Stepwise linear regression identified asymmetry of activation for encoding words and faces in the ipsilateral anterior medial temporal lobe as strongest predictors for postoperative verbal and visual memory decline. Activation asymmetry, language lateralization and performance on preoperative neuropsychological tests predicted clinically significant verbal memory decline in all patients who underwent left anterior temporal lobe resection, but were less able to predict visual memory decline after right anterior temporal lobe resection. Preoperative memory functional magnetic resonance imaging was the strongest predictor of verbal and visual memory decline following anterior temporal lobe resection. Preoperatively, verbal and visual memory function utilized the damaged, ipsilateral hippocampus and also the contralateral hippocampus. Memory function in the ipsilateral posterior hippocampus may contribute to better preservation of memory after surgery.
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10.1093/brain/awq006
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10335742
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The SF-36 Arthritis-Specific Health Index (ASHI): I. Development and cross-validation of scoring algorithms.
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An arthritis-specific health index (ASHI) for the SF-36 Health Survey was developed by studying its responsiveness to changes in clinical indicators of arthritis severity. Longitudinal data from 1,076 patients participating in four placebo-controlled trials were analyzed. All had at least a 6-month history of moderate to severe osteoarthritis or rheumatoid arthritis of the knee or hip. All had undergone a washout period of 3 to 14 days before baseline assessment to bring about a flare state in osteoarthritis or rheumatoid arthritis symptoms. Their average age was 60 years and 72% were female. Change scores for the eight-scale SF-36 health profile (acute version) and five arthritis-specific measures of disease severity (knee pain on weight bearing, time to walk 50 feet, physician global evaluation of symptom severity and impact, patient global evaluation of symptom severity and impact, and pain intensity visual analogue scale) were computed by subtracting scores before treatment from scores at two-week follow-up. Canonical correlation methods were used to derive weights for changes in SF-36 scales to score a single index (ASHI) that maximized its correlation with changes in the set of five clinical measures of arthritis severity. The weights used to score the ASHI were cross-validated in a 25% holdout group (N = 144) from the first two osteoarthritis trials and in two additional osteoarthritis and rheumatoid arthritis trials (N = 530). Only one SF-36 canonical variate (ASHI) correlated significantly (F = 4.69, P < 0.0001) with the clinical canonical variate that served as the "criterion" measure of change in the severity of arthritis. Changes in the ASHI and clinical canonical variate were substantially correlated in the developmental sample (r = 0.628, P < 0.0001) and on cross-validation (r = 0.629, P < 0.0001). The clinical canonical variate correlated highly (r = 0.75-0.88) with changes in all but one of the five clinical measures (50-foot walk; r = 0.41). The pattern of correlations between changes in SF-36 scales and the ASHI indicated that ASHI is primarily a measure of bodily pain (r = 0.92) and other aspects of physical and role functioning and well-being (r = 0.69 for Role-Physical, r = 0.68 for Physical Functioning, r = 0.52 for Social Functioning, and r = 0.51 Vitality). The patterns of correlations between SF-36 scales and the ASHI were very similar across developmental and cross-validation samples. This research demonstrates the feasibility and generalizability of a single ASHI scored from changes in responses to the SF-36 Health Survey. The generic SF-36 health profile, which has already been shown to be useful in comparing arthritis with other diseases and treatments, can also be scored specifically to make it more useful in studies of osteoarthritis and rheumatoid arthritis.
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10.1097/00005650-199905001-00004
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35888454
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How Porphyromonas gingivalis Navigate the Map: The Effect of Surface Topography on the Adhesion of Porphyromonas gingivalis on Biomaterials.
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The main purpose of this study is to develop an understanding of how Porphyromonas gingivalis responds to subperiosteal implant surface topography. A literature review was drawn from various electronic databases from 2000 to 2021. The two main keywords used were " Porphyromonas gingivalis " and "Surface Topography". We excluded all reviews and or meta-analysis articles, articles not published in English, and articles with no surface characterization process or average surface roughness (R a ) value. A total of 26 selected publications were then included in this study. All research included showed the effect of topography on Porphyromonas gingivalis to various degrees. It was found that topography features such as size and shape affected Porphyromonas gingivalis adhesion to subperiosteal implant materials. In general, a smaller R a value reduces Porphyromonas gingivalis regardless of the type of materials, with a threshold of 0.3 µm for titanium.
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10.3390/ma15144988
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12814365
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Differential modulation of NMDA-induced calcium transients by arachidonic acid and nitric oxide in cultured hippocampal neurons.
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We have examined the effect of arachidonic acid on the transient increases in intracellular Ca2+ evoked by NMDA and AMPA in cultured hippocampal pyramidal cells loaded with Fura-2 AM. Repeated brief pulses of NMDA elicited Ca2+ transients that showed a modest run down. This run down was enhanced if the preparation was shielded from UV light and was reduced by conducting the experiments in the presence of the nitric oxide synthase inhibitor l-nitroarginine (100 micro m). Arachidonic acid (2 micro m) enhanced the Ca2+ transients evoked by NMDA but not those evoked by AMPA. Other C20 unsaturated fatty acids did not alter the time course of the response to NMDA. These experiments suggest that elevated intracellular Ca2+ activates nitric oxide synthase and the resulting synthesis of nitric oxide depresses the Ca2+ response to NMDA while arachidonic acid augments these responses. Therefore two substances implicated in synaptic plasticity (arachidonic acid and nitric oxide) differentially modulate NMDA-mediated Ca2+ entry into hippocampal neurons.
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10.1046/j.1460-9568.2003.02671.x
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12424745
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Comparative effect of dietary administration of Lathyrus sativus pulse on behaviour, neurotransmitter receptors and membrane permeability in rats and guinea pigs.
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Neurolathyrism, an upper motor neuron disease, has been thought to be caused by long-term dietary consumption of lathyrus pulse, which contains the toxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid. Earlier behavioural studies employing oral feeding of lathyrus pulse to animals has been conducted without evaluating the biochemical toxicity potential. In the present investigation the effect of dietary feeding of 10%, 50% and 80% lathyrus pulse to rats and guinea pigs for 3 months on neurobehavioural parameters, including locomotor activity, inclined plain test and neurotoxicological parameters such as neurotransmitter receptor binding, Ca(2+) influx and membrane fluidity, was investigated. Exposure of 50% low and high toxin lathyrus to rats did not cause any significant change in locomotor activity, whereas guinea pigs at the same dosage regimen of high toxin lathyrus showed significant lowering of inclined plain test scores. Furthermore, studies of neuroreceptor binding in rats fed 50% low and high toxin lathyrus showed significant changes in glutamate, dopamine and muscarinic receptors, whereas the benzodiazepine receptor elicited no change. Guinea pigs, on the other hand, fed 50% and 80% lathyrus in the diet showed significant changes in glutamate, dopamine, muscarinic and benzodiazepine receptors. Interestingly, significant elevation in intracellular calcium with a concomitant increase in membrane fluidity was observed in rats (50% low and high toxin) and guinea pigs (50% and 80%) fed a lathyrus diet. These results indicate that although both species (rats and guinea pigs) are susceptible to neurochemical changes on exposure to lathyrus, locomotor changes are only noticed in guinea pigs. Thus, guinea pigs may be more prone to lathyrus toxicity and may serve as a sensitive animal model compared with rats. Copyright 2002 John Wiley & Sons, Ltd.
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10.1002/jat.878
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33524301
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Prognosis of Ocular Tuberculosis Following Long-Term Antitubercular Therapy.
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Purpose: This study presents clinical features and prognosis after long-term (12-18 months) antitubercular therapy (ATT) in patients with ocular tuberculosis (OTB) in East China, an endemic area of tuberculosis. Methods: This retrospective study reviewed data from OTB patients treated at the Eye and ENT Hospital of Fudan University from 2008 to 2018. All the patients completed a minimum follow-up of 6 months after the cessation of ATT. Results: Sixty-six patients with OTB were studied. The ocular manifestations included retinal vasculitis (51.6%), choroiditis (24.2%), panuveitis (23.2%), intermediate uveitis (7.4%), scleritis (5.3%), anterior uveitis (2.1%), and optic neuropathy (1%). Except for two patients (ATT for 6 months), all other patients (64/66, 96.97%) received ATT for at least 12 months (6 patients for 12 months, 30 patients for 15 months, and 28 patients for 18 months). Treatment in conjunction with oral corticosteroids was used in 48 patients (72.7%). The average initial best-corrected visual acuity (BCVA) was 0.8 ± 0.64 (LogMAR), which improved to 0.31 ± 0.35 (LogMAR) at the last follow-up ( P < 0.05). The final BCVA was significantly associated with the initial BCVA and the duration of clinical symptoms. A complete remission of uveitis was achieved in 97% of the patients. Conclusions: This study observed a favorable prognosis with long-term ATT regimens. Patients with better baseline visual acuity and a shorter duration of clinical symptoms before diagnosis had a better prognosis.
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10.1089/jop.2020.0100
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10598967
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AV node ablation and pacemaker implantation after withdrawal of effective rate-control medications for chronic atrial fibrillation: effect on quality of life and exercise performance.
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We assess whether AV node ablation and pacemaker implantation after discontinuation of effective rate-control medical therapy for chronic atrial fibrillation had a positive impact on quality of life and exercise performance. To assess the possibility of a placebo effect following pacemaker implantation, the study included three groups of patients. Group 1 underwent an echocardiogram, treadmill exercise, and quality of life measurement 1 month prior to and 6 months following AV node ablation and pacemaker implantation associated with discontinuation of rate-control medications. Group 2 underwent AV node ablation and pacemaker implantation without discontinuation of antiarrhythmic rate-control drugs. Group 3 underwent pacemaker implantation without performing AV node ablation and continuing rate-control medical therapy. At the 1- and 6-month evaluation, the patients in group 1 showed a significant improvement of left ventricular ejection fraction, quality of life, and activity scores. The exercise duration and the maximal VO2 consumption, however, did not change significantly. A slight improvement of the quality of life and physical activity scores was observed in the group undergoing AV node ablation without withdrawal of medications. However, no significant changes were observed in the group receiving only the pacemaker without modification of medical therapy and with intact AV node conduction. In conclusion, in patients with chronic atrial fibrillation, discontinuation of effective rate-control medical therapy followed by AV node ablation and permanent pacing appeared to improve quality of life and activity scores despite no change in exercise duration. The improvement observed does not seem to reflect a placebo effect.
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10.1111/j.1540-8159.1999.tb00383.x
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27248298
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Marriage, violence and HIV: the shifting policy context in Uganda.
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The policy environment for vulnerable women in Uganda is rapidly changing, with the aim of introducing more punitive measures for violent offenders and more options for women seeking help. This paper examines HIV-positive women who experienced intimate partner violence in two regions of Uganda prior to the enactment of the Domestic Violence Act of 2010. Based on in-depth interviews and observations, it reports on women's views of marriage and relationships, and their strategies for help seeking to show the interaction between the two phenomena within the local cultural and political context. HIV-positive women in Uganda reshape their notions of marriage and love based on experiences of violence, illness management and broader social factors. Their narratives of relationships and conflict reveal an ambivalence toward formal marriage because of both its security and rights and its potential to inhibit leaving, as well as a reluctance to seek help through formal means. This construction of marriage is intertwined with the shifting social backdrop in Uganda, in particular the increasing rollout of antiretroviral treatment for HIV and the development of new policies surrounding violence, marriage and divorce. Women's experiences show potential points of intervention and the need for multi-sectoral responses to violence.
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10.1080/13691058.2016.1184313
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2096499
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Clinical efficacy of mefloquine in children suffering from chloroquine-resistant Plasmodium falciparum malaria in Nigeria.
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One hundred and thirteen children with symptomatic uncomplicated falciparum malaria were treated with either chloroquine 25 mg/kg body weight over 3 d (51 subjects) or mefloquine 25 mg/kg body weight single dose (62 subjects). The cure rate in the chloroquine group was 65% and in the mefloquine group 100%. 14 patients with chloroquine-resistant falciparum malaria (7 RI, 6 RII and one RIII) were successfully treated with mefloquine. The clearance times of parasitaemia and fever were 60 +/- 21.5 h and 24.7 +/- 10.1 h respectively in the chloroquine-sensitive group and 52.3 +/- 18.2 h and 24.5 +/- 23.7 h respectively in the mefloquine group. In the chloroquine-resistant group treated successfully with mefloquine, these clearance times were 44.0 +/- 8.9 and 24.0 h respectively. The only remarkable adverse reaction in the chloroquine group was pruritus which occurred in 7 subjects. Abdominal pain and diarrhoea (8 subjects) and dizziness (3 subjects) were the only important adverse reactions in the mefloquine group. It is concluded that, despite previous reports of primary reduced susceptibility to mefloquine in vitro of some West African isolates of Plasmodium falciparum, this drug may be useful in the treatment of both chloroquine-sensitive and chloroquine-resistant falciparum malaria in West Africa.
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10.1016/0035-9203(90)90067-o
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17975144
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The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer.
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We previously identified three genes, HOXB13, IL17BR, and CHDH, that strongly predict clinical outcome in estrogen receptor (ER)-positive breast cancer patients receiving tamoxifen monotherapy. The biological mechanisms linking these genes to estrogen signaling and tamoxifen response in breast cancer remain to be determined. In a consecutive series of 148 ER-positive and ER-negative breast cancers, HOXB13, IL17BR, and CHDH gene expression was measured by quantitative real-time PCR and correlated with ER, PR, and HER2 expression. The role of estrogen and ER in the regulation of these three genes was assessed in several ER-positive and ER-negative breast cancer cell lines. In primary breast tumors, HOXB13 expression correlated negatively, and IL17BR and CHDH expression correlated positively, with ER status, and all three genes exhibited an ER-dependent correlation pattern with HER2 status that differs from PR and PS2, two canonical estrogen-regulated genes. Results using breast cancer cell lines show that these genes are regulated by estradiol in an ER-dependent manner, and that this regulation is abrogated by tamoxifen. HOXB13, IL17BR, and CHDH are estrogen-regulated genes, but their pattern of correlation with known positive (ER, PR) and negative (HER2) predictors of tamoxifen response differs from canonical ER signature genes. These results provide a biological rationale for the prognostic utility of these three genes in early-stage ER-positive breast cancer and for their potential to predict anti-estrogen resistance.
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10.1158/1078-0432.CCR-07-0310
|
18784478
|
Transcranial Doppler ultrasonography: a diagnostic tool of increasing utility.
|
Since its introduction in 1982, transcranial Doppler ultrasonography has become an important diagnostic and monitoring tool in patients with surgical disease. It has applications in the perioperative period, as well as in the intensive care unit. It is therefore appropriate for the anesthesiologist to maintain an understanding of its current utility. Transcranial Doppler has an established role in diagnosing cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage and for guiding transfusion therapy in children with sickle cell disease. It has application in the preoperative evaluation of patients with cerebrovascular disease, as well as that of an intraoperative monitor in carotid endarterectomy and carotid stenting. It is useful for detecting right-to-left shunts in settings in which transesophageal echocardiography is not desirable. Its value in settings such as traumatic brain injury, hepatic failure, and migraine headache has yet to be fully clarified. Although there are several settings in which transcranial Doppler has well established usefulness, there are many more in which it is likely valuable, such as traumatic brain injury, ischemic stroke, and fulminant hepatic failure. Further research is needed in these fields to elucidate the exact role for transcranial Doppler.
|
10.1097/ACO.0b013e32830edc0b
|
23728871
|
Evidence-based treatment strategies in idiopathic pulmonary fibrosis.
|
Recently updated guidelines have provided revised recommendations, based on the GRADE criteria, for the diagnosis and pharmacological and non-pharmacological management of patients with idiopathic pulmonary fibrosis (IPF). Cochrane reviews are also a highly respected and reliable source of evidence-based information that identify and analyse all available data of overall treatment effects from appropriate studies. A recent update of one Cochrane review failed to identify any new evidence supporting the use of corticosteroids in IPF. Another review of data from 15 randomised controlled studies of non-steroid agents for the treatment of IPF identified two trials of interferon-γ-1b suitable for analysis. However, the pooled analysis revealed no treatment effect in terms of survival. A further meta-analysis of three phase III studies of pirfenidone treatment in IPF patients suggested a significant increase in progression-free survival. The interpretation of recent international and national European guideline updates and treatment recommendations, available clinical data from published and ongoing trials investigating potential pharmacological agents, and the individual patient's preferences, must be considered in the clinical management of this disease.
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10.1183/09059180.00001013
|
25990190
|
Impact of an Overnight Internal Medicine Academic Hospitalist Program on Patient Outcomes.
|
Many academic hospitals have implemented overnight hospitalists to supervise house staff and improve outcomes, but few studies have described the impact of this role. To investigate the effect of an overnight academic hospitalist program on patient-level outcomes. Secondary objectives were to describe the program's revenue generation and work tasks. Retrospective interrupted time-series analysis of patients admitted to the medicine service before and after implementation of the program. All patients aged 18 and older admitted to the acute or intermediate care units between 7:00 p. m. and 6:59 a. m. during the period before (April 2011-August 2012) and after (September 2012-April 2014) program implementation. An on-site attending-level physician directly supervising medicine house staff overnight, providing clinical care during high-volume periods, and ensuring safe handoffs to daytime providers. Primary outcomes included in-hospital mortality, 30-day hospital readmissions, length of stay, and upgrades in care on the night of admission and during hospitalization. Multivariable models estimated the effect on outcomes after adjusting for secular trends. Revenue generation and work tasks are reported descriptively. During the study period, 6484 patients were admitted to the medicine service: 2722 (42 %) before and 3762 (58 %) after implementation. No differences were found in mortality (1.1 % vs. 0.9 %, p=0.38), 30-day readmissions (14.8 % vs. 15.6 %, p=0.39), mean length of stay (3.09 vs. 3.08 days, p=0.86), or upgrades to intensive care on the night of admission (0.4 % vs. 0.7 %, p=0.11) or during hospitalization (3.5 % vs. 4.2 %, p=0.20). During the first year, hospitalists billed 1209 patient encounters (3.3/shift) and 63 procedures (0.2/shift), and supervised 1939 patient admissions (6.12/shift) while supervising house staff 3-h/shifts. Implementation of an overnight academic hospitalist program showed no impact on several important clinical outcomes, and revenue generation was modest. As overnight hospitalist programs develop, investigations are needed to delineate the return on investment and focus on other outcomes that may be more sensitive to change, such as errors and provider/patient satisfaction.
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10.1007/s11606-015-3389-0
|
33348939
|
Parry-Romberg syndrome: a mini review.
|
Parry-Romberg syndrome (PRS) is a rare disorder of uncertain etiology that is characterized by progressive atrophy of the soft and hard tissues of face, typically occurring in the first 2 decades of life. It is more commonly seen in females. The disease progresses slowly with gradual atrophy, frequently associated with neurological, ophthalmological, and other system involvement, resulting in secondary complications. The severity of deformity varies depending on the age of onset of disease. Those in whom the disease starts at an earlier age will have more severe deformity. Due to the visible facial deformity, such patients usually suffer from social and psychological trauma. Management is mainly cosmetic, which is carried out after disease progression has stopped and stabilized. This brief review describes PRS in detail and compares it with linear morphea en coup de sabre (ECDS), its close differential, which is likely to be a milder variant sharing the same spectrum of disease.
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33859481
|
Evaluation of Wet Mount and Concentration Techniques of Stool Examination for Intestinal Parasites Identification at Debre Markos Comprehensive Specialized Hospital, Ethiopia.
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Intestinal parasitic infection has serious medical and public health impacts in developing countries. Intestinal parasites were under reported via direct wet mount method due to its poor sensitivity. So, the selection of a more sensitive and reliable diagnostic method is essential. The aim of the study was to evaluate the diagnostic performance of wet mount and concentration techniques of stool examination for intestinal parasites identification. A cross-sectional study among 797 pregnant women was conducted from October 2018 to February 2019 at Debre Markos Comprehensive Specialized Hospital. The study participants were selected by using a systematic random sampling technique. Stool sample was processed by using Wet Mount (WM) and Formol-Ether Concentration (FEC) techniques. Data was entered into Epi-data version 3.1 and analysis using SPSS version 20.0. The sensitivity, specificity, positive predictive value, and negative predictive value were determined against the combined result as "Gold" standard. Kappa value was determined to estimate the agreement of the diagnostic methods. The overall prevalence of intestinal parasites (IP) was 35.2% with a combined method. By using WM and FEC the prevalence of IP was 13.1% and 25.7%, respectively. The sensitivity and negative predictive value of WM method were 37.1% and 74.6%, and for FEC method 73.5% and 87.5%, respectively. Test efficiency of direct WM and FEC were 77.9% and 90.7%, respectively. The agreement of WM and FEC techniques with combined technique were moderate (κ=0.434) and perfect (κ=0.783), respectively. The prevalence of intestinal parasites was under-reported by wet mount technique. The diagnostic performance of FEC technique for the diagnosis of intestinal parasites in pregnant women was notably high as compared to WM technique in the present study. Therefore, the WM and FEC combined method should be used as a routine diagnostic technique for the diagnosis of intestinal parasites identification. © 2021 Demeke et al.
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10.2147/IDR.S307683
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32647601
|
An Evaluation of Assistive Technology in Determining Job-Specific Preference for Adults With Autism and Intellectual Disabilities.
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The transition to employment can be difficult for adults with autism spectrum disorders (ASDs) and intellectual disabilities (IDs). Currently, a limited number of ASD-specific career-planning tools exist within the literature, creating a challenge in terms of accurately identifying jobs that match individual preferences and strengths. This study evaluated the effects of a technology-based prework assessment on job performance among 3 adults with ASD and ID, aged 20-21 years prior to beginning supported employment. Three job conditions were established: a high-preference, high-skill-match job; a high-preference, low-skill-match job; and a low-preference, low-skill-match job. The 3 job conditions were evaluated using an alternating-treatments design with supported-employment sessions counterbalanced across a 6-week period. The results indicated that the high-preference job conditions produced higher levels of job performance irrespective of skill match. Implications for future research and practice are discussed. © Association for Behavior Analysis International 2019.
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10.1007/s40617-019-00380-3
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7894301
|
New techniques of ultrasound and color Doppler in the prospective evaluation of acute renal obstruction. Do they replace the intravenous urogram?
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The intravenous urogram has long been the primary imaging modality in assessing acute renal obstruction. Newer ultrasound (US) techniques including pulsed and color Doppler allow the physiology of the urinary system to be interrogated via the resistive indices and ureteral jets. We sought to determine whether these new techniques would improve the ability of ultrasound to assess the presence of renal obstruction and replace the intravenous urogram in assessing acute ureteral obstruction. 32 patients suspected of having acute renal obstruction were evaluated with US and a KUB. A prospective diagnosis of complete, partial, or no obstruction was made. An intravenous urogram (IVU) was then performed as the "gold standard" for comparison. Complete obstruction was correctly identified by the absence of a ureteral jet with no false negative studies. Using our ultrasound KUB protocol, partial obstruction was correctly identified in 77% of patients. All nonobstructed patients were correctly diagnosed. The overall sensitivity of combined ultrasound and KUB analysis was 84%, specificity 85%, and accuracy 87.5%. Contemporary ultrasound employing pulsed and color Doppler is tedious and requires expertise not always available. Results with the intravenous urogram are more sensitive than specific. Unless contrast material is contraindicated, acute obstruction is best evaluated with intravenous urography.
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10.1007/BF00199647
|
27249814
|
Acute myocarditis with normal wall motion detected with 2D speckle tracking echocardiography.
|
SummaryWe present the case of a 26-year-old male with acute tonsillitis who was referred for coronary angiography because of chest pain, elevated cardiac biomarkers, and biphasic T waves. The patient had no cardiovascular risk factors. Echocardiography showed no wall motion abnormalities and no pericardial effusion. 2D speckle tracking revealed distinct decreased regional peak longitudinal systolic strain in the lateral and posterior walls. Ischemic disease was extremely unlikely in view of his young age, negative family history regarding coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram. Coronary angiography was deferred as myocarditis was suspected. To confirm the diagnosis, cardiac magnetic resonance tomography (MRT) was performed, showing subepicardial delayed hyperenhancement in the lateral and posterior walls correlating closely with the strain pattern obtained by 2D speckle tracking echocardiography. With a working diagnosis of acute myocarditis associated with acute tonsillitis, we prescribed antibiotics and nonsteroidal anti-inflammatory drugs. The patient's clinical signs resolved along with normalization of serum creatine kinase (CK) levels, and the patient was discharged on the third day after admission. Acute myocarditis can mimic acute coronary syndromes. Conventional 2D echocardiography lacks specific features for detection of subtle regional wall motion abnormalities.2D speckle tracking expands the scope of echocardiography in identifying myocardial dysfunction derived from edema in acute myocarditis. © 2016 The authors.
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10.1530/ERP-16-0013
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18972868
|
[Therapeutic approaches for treatment of Creutzfeldt-Jakob disease].
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A multiplicity of different chemical agents have shown positive effects in vivo in the treatment of prion diseases. However, some properties make implementation in clinical studies difficult, such as toxic effects or missing penetration of the blood-brain barrier. Thus, further studies are concentrating on the development of derivatives with less toxicity and good penetration of the blood-brain barrier. In part some clinical studies have shown positive effects, whereas other agents had no effect on survival time as the major aim of treatment. Difficulties in assessment of possible effects turn up especially in agents which were tested only in single patients. Promising preliminary results are indicated for the treatment with doxycycline.
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26132161
|
Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to Malignancy.
|
Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response.
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10.1371/journal.pone.0128300
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23263110
|
Optical performance monitoring for OFDM using low bandwidth coherent receivers.
|
We propose using low bandwidth coherent receivers for distributed optical performance monitoring. We demonstrate optical signal-to-noise ratio (OSNR) monitoring of both 20-Gb/s single-polarization and 40-Gb/s polarization-multiplexed coherent optical orthogonal frequency-division multiplexing (CO-OFDM) signals with a 0.8-GHz receiver using both data-aided (DA) and non-data-aided (NDA) approaches. The sampling rate of the performance monitor is much lower than the signal baud rate, so provides a cost-effective solution for distributed optical performance monitoring. The proposed method is demonstrated experimentally and through simulation. The results show that after calibration the OSNR monitoring error is less than 1 dB and the two approaches are not affected by fiber dispersion after 800-km transmission and 30-ps differential group delay (DGD).
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10.1364/OE.20.028724
|
38474331
|
Comparative Analysis of Acute Kidney Injury Models and Related Fibrogenic Responses: Convergence on Methylation Patterns Regulated by Cold Shock Protein.
|
Fibrosis is characterized by excessive extracellular matrix formation in solid organs, disrupting tissue architecture and function. The Y-box binding protein-1 (YB-1) regulates fibrosis-related genes (e. g., Col1a1, Mmp2, and Tgfβ1 ) and contributes significantly to disease progression. This study aims to identify fibrogenic signatures and the underlying signaling pathways modulated by YB-1. Transcriptomic changes associated with matrix gene patterns in human chronic kidney diseases and murine acute injury models were analyzed with a focus on known YB-1 targets. Ybx1 -knockout mouse strains ( Ybx1 ΔRosaERT+TX and Ybx1 ΔLysM ) were subjected to various kidney injury models. Fibrosis patterns were characterized by histopathological staining, transcriptome analysis, qRT-PCR, methylation analysis, zymography, and Western blotting. Integrative transcriptomic analyses revealed that YB-1 is involved in several fibrogenic signatures related to the matrisome, the WNT, YAP/TAZ, and TGFß pathways, and regulates Klotho expression. Changes in the methylation status of the Klotho promoter by specific methyltransferases (DNMT) are linked to YB-1 expression, extending to other fibrogenic genes. Notably, kidney-resident cells play a significant role in YB-1-modulated fibrogenic signaling, whereas infiltrating myeloid immune cells have a minimal impact. YB-1 emerges as a master regulator of fibrogenesis, guiding DNMT1 to fibrosis-related genes. This highlights YB-1 as a potential target for epigenetic therapies interfering in this process.
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10.3390/cells13050367
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28366438
|
Measuring joint kinematics of treadmill walking and running: Comparison between an inertial sensor based system and a camera-based system.
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Inertial sensor systems are becoming increasingly popular for gait analysis because their use is simple and time efficient. This study aimed to compare joint kinematics measured by the inertial sensor system RehaGait® with those of an optoelectronic system (Vicon®) for treadmill walking and running. Additionally, the test re-test repeatability of kinematic waveforms and discrete parameters for the RehaGait® was investigated. Twenty healthy runners participated in this study. Inertial sensors and reflective markers (PlugIn Gait) were attached according to respective guidelines. The two systems were started manually at the same time. Twenty consecutive strides for walking and running were recorded and each software calculated sagittal plane ankle, knee and hip kinematics. Measurements were repeated after 20min. Ensemble means were analyzed calculating coefficients of multiple correlation for waveforms and root mean square errors (RMSE) for waveforms and discrete parameters. After correcting the offset between waveforms, the two systems/models showed good agreement with coefficients of multiple correlation above 0.950 for walking and running. RMSE of the waveforms were below 5° for walking and below 8° for running. RMSE for ranges of motion were between 4° and 9° for walking and running. Repeatability analysis of waveforms showed very good to excellent coefficients of multiple correlation (>0.937) and RMSE of 3° for walking and 3-7° for running. These results indicate that in healthy subjects sagittal plane joint kinematics measured with the RehaGait® are comparable to those using a Vicon® system/model and that the measured kinematics have a good repeatability, especially for walking. Copyright © 2017 Elsevier Ltd. All rights reserved.
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10.1016/j.jbiomech.2017.03.015
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32602645
|
Between a rock and a hard place: adaptive sensing and site-specific dispersal.
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Environmental variability can lead to dispersal: why stay put if it is better elsewhere? Without clues about local conditions, the optimal strategy is often to disperse a set fraction of offspring. Many habitats contain environmentally differing sub-habitats. Is it adaptive for individuals to sense in which sub-habitat they find themselves, using environmental clues, and respond plastically by altering the dispersal rates? This appears to be done by some plants which produce dimorphic seeds with differential dispersal properties in response to ambient temperature. Here we develop a mathematical model to show, that in highly variable environments, not only does sensing promote plasticity of dispersal morph ratio, individuals who can sense their sub-habitat and respond in this way have an adaptive advantage over those who cannot. With a rise in environmental variability due to climate change, our understanding of how natural populations persist and respond to changes has become crucially important. © 2020 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.
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10.1111/ele.13564
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31472902
|
Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome.
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Steroid-resistant nephrotic syndrome is a frequent cause of chronic kidney disease almost inevitably progressing to end-stage renal disease. More than 58 monogenic causes of SRNS have been discovered and majority of known steroid-resistant nephrotic syndrome causing genes are predominantly expressed in glomerular podocytes, placing them at the center of disease pathogenesis. Herein, we describe two unrelated families with steroid-resistant nephrotic syndrome with homozygous mutations in the KIRREL1 gene. One mutation showed high frequency in the European population (minor allele frequency 0.0011) and this patient achieved complete remission following treatment, but later progressed to chronic kidney disease. We found that mutant KIRREL1 proteins failed to localize to the podocyte cell membrane, indicating defective trafficking and impaired podocytes function. Thus, the KIRREL1 gene product has an important role in modulating the integrity of the slit diaphragm and maintaining glomerular filtration function. Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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10.1016/j.kint.2019.06.016
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21818597
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Thoracolumbar imbalance analysis for osteotomy planification using a new method: FBI technique.
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Treatment of spine imbalance by posterior osteotomy is a valuable technique. Several surgical techniques have been developed and proposed to redress the vertebral column in harmonious kyphosis in order to recreate correct sagittal alignment. Although surgical techniques proved to be adequate, preoperative planning still is mediocre. Multiple suggestions have been proposed, from cutting tracing paper to ingenious mathematical formulas and computerised models. The analysis of the pelvic parameters to try to recover the initial shape of the spine before the spine imbalance occurred is very important to avoid mistakes during the osteotomy planification. The authors proposed their method for the osteotomy planning paying attention to the pelvic, and spine parameters and in accordance with Roussouly's classification. The pre operative planning is based on a full-body X-ray including the spine from C1 to the femoral head and the first 10 cm of the femur shaft. Using all the balance parameters provided, a formula name FBI is proposed. Calculation of the osteotomy is basic goniometry, the midpoint of the C7 inferior plateau (point a) is transposed horizontally on the projected future C7 plumb line (point b) crossing posterior S1 plateau on a sagittal X-ray. These are the first two reference points. A third reference point is made on the anterior wall of the selected vertebra for osteotomy at mid height of the pedicle (point c) mainly L4 vertebra. These three points form a triangle with the tip being the third reference point. The angle represented by this triangle is the theoretical angle of the osteotomy. Two more angles should be measured and eventually added. The femur angulation measured as the inclination of the femoral axis to the vertical. And a third angle named the compensatory pelvic tilt to integrate the type of pelvis. If the pelvic tilt is between 15 and 25° or is higher than 25° you must add 5 or 10°, respectively. This compensatory tilt is based on a clinical analysis of operated patients. This planification was applied in a retrospective study of 18 patients and showed why in some cases improper correction was performed and prospectively in 8 cases with good clinical outcomes and correct spinal alignment. Sometimes it is necessary to find an acceptable compromise when rebalancing the spine paying attention to the general parameters of the patients like: age, osteoporosis, systemic disease etc. This FBI technique can be used even for small lordosis restoration: it gave a good evaluation of the amount of correction needed and then the surgeon had the choice to use the appropriate technique to obtain a good balance.
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10.1007/s00586-011-1935-y
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37176504
|
Cardioselective versus Non-Cardioselective Beta-Blockers and Outcomes in Patients with Atrial Fibrillation and Chronic Obstructive Pulmonary Disease.
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Atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) have been independently associated with increased mortality; however, there is no evidence regarding beta-blocker cardioselectivity and long-term outcomes in patients with AF and concurrent COPD. Methods: This post hoc analysis of the MISOAC-AF randomized trial (NCT02941978) included patients hospitalized with comorbid AF. At discharge, all patients were classified according to the presence of COPD; patients with COPD on beta-blockers were classified according to beta-blocker cardioselectivity. Adjusted hazard ratios (aHRs) were calculated by using multivariable Cox regression models. The primary outcome was all-cause mortality, and the secondary outcomes were cardiovascular mortality and hospitalizations. Results: Of 1103 patients with AF, 145 (13%) had comorbid COPD. Comorbid COPD was associated with an increased risk of all-cause (aHR, 1.33; 95% confidence interval (CI), 1.02 to 1.73) and cardiovascular mortality (aHR 1.47; 95% CI, 1.10 to 1.99), but not with increased risk of hospitalizations (aHR 1.10; 95% CI, 0.82 to 1.48). The use of cardioselective versus non-cardioselective beta-blockers was associated with similar all-cause mortality (aHR 1.10; 95% CI, 0.63 to 1.94), cardiovascular mortality (aHR 1.33; 95% CI, 0.71 to 2.51), and hospitalizations (aHR 1.65; 95% CI 0.80 to 3.38). Conclusions: In recently hospitalized patients with AF, the presence of COPD was independently associated with increased risk of all-cause and cardiovascular mortality. No difference between cardioselective and non-cardioselective beta-blockers, regarding clinical outcomes, was identified.
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10.3390/jcm12093063
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27987448
|
The optimization, kinetics and mechanism of m-cresol degradation via catalytic wet peroxide oxidation with sludge-derived carbon catalyst.
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The sludge-derived carbon catalyst modified with 0°C HNO 3 solution was tested in catalytic wet peroxide oxidation of m-cresol (100mgL -1 ) with systematical mathematical models and theoretical calculation for the first time. The reaction conditions were optimized by response surface methodology (RSM) as T=60°C, initial pH=3.0, C 0,H2O2(30%) =1.20gL -1 (lower than the stoichiometric amount of 1.80gL -1 ) and C cat =0.80gL -1, with 96% of m-cresol and 47% of TOC converted after 16min and 120min of reaction, respectively, and ξ (mg TOC/g H 2 O 2 fed)=83.6mg/g. The end time of the first kinetic period in m-cresol model was disclosed to be correlated with the fixed residue m-cresol concentration of about 33%. Furthermore, the kinetic constants in models of TOC and H 2 O 2 exactly provide convincing proof of three-dimensional response surfaces analysis by RSM, which showed the influence of the interaction between organics and H 2 O 2 on effective H 2 O 2 utilization. The reaction intermediates over time were identified by gas chromatography-mass spectrometer based on kinetics analysis. Four degradation pathways for m-cresol were proposed, of which the possibility and feasibility were well proven by frontier molecule orbital theory and atomic charge distribution via density functional theory method. Copyright © 2016 Elsevier B. V. All rights reserved.
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10.1016/j.jhazmat.2016.12.014
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26074410
|
Characterization of Salmonella enterica serovar Typhimurium and Salmonella enterica serovar 4,[5],12:i:- isolates from pigs presenting with diarrhea in Korea.
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Between 2011 and 2012, a total of 896 pig fecal samples were collected from nine provinces in Korea, and 50 salmonella enterica susp. enterica serovar Typhimurium (S. Typhimurium) was isolated. The characteristics of the 50 strains were analyzed, and 4 strains were identified as Salmonella enterica subsp. enterica serovar 4,[5],12:i:-. Salmonella 4,[5],12:i:- could not be distinguished from S. Typhimurium through phage typing, antimicrobial resistance testing or multiple-locus variable-number tandem repeat analysis (MLVA). However, among the four Salmonella 4,[5],12:i:- strains, one (KVCC-BA1400078) was identified as a Salmonella 4,[5],12:i:- clone isolated from humans in the United States, and another (KVCC-BA1400080) was identified as DT193, which has been primarily isolated from humans and animals in European countries. The presence of Salmonella 4,[5],12:i:- in Korea poses a significant threat of horizontal transfer between pigs and humans.
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10.1292/jvms.15-0151
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2883284
|
Comparison of changes in locomotor activity with striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations following the bilateral intranigral injection of dopamine agonist drugs in rats.
|
Bilateral injection of apomorphine (2.5 micrograms) into the substantia nigra zona reticulata of rats reduced both locomotor activity and striatal HVA and DOPAC concentrations. Bilateral injection of dopamine (10 micrograms) did not affect locomotor activity whereas a higher dose of dopamine (50 micrograms) enhanced locomotor activity. Striatal HVA and DOPAC concentrations were unchanged following injection of dopamine. Bilateral injection of (+/-)-3PPP (0.1 or 2.5 micrograms) into the zona reticulata of the substantia nigra did not alter locomotor activity while a higher dose (10 micrograms) enhanced locomotion. Injection of (+/-)-3PPP (0.1-10 micrograms) into the zona reticulata was without effect on striatal HVA or DOPAC concentrations. The bilateral manipulation of nigral dopaminergic neurotransmission alters motor activity and nigrostriatal dopamine turnover in conscious rats. However, the changes in motor activity are not necessarily related to altered nigrostriatal activity, suggesting the involvement of dopamine receptors located at non-dopaminergic sites within the substantia nigra.
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10.1111/j.2042-7158.1987.tb06248.x
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25408859
|
Diagnosis and subclassification of acute lymphoblastic leukemia.
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Acute lymphoblastic leukemia (ALL) is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly between ALL subsets, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT) and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review summarizes how best to identify ALL and the most relevant ALL subsets.
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10.4084/MJHID.2014.073
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21508561
|
Ecofriendly decolorisation of Cr-complex dye Acid Black 172 by a newly isolated Pseudomonas sp. strain DY1.
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Pseudomonas sp. strain DY1 was newly isolated from soil with rotten wood and identified as a member of the genus Pseudomonas based on 16S rDNA and biochemical tests. Acid Black 172, a water soluble Cr-complex dye, was then selected as a model dye to investigate the decolorisation ability of the strain. It was observed that the growth of the strain was not inhibited by high dose of metal ions (10 mM), and efficient decolorisation was still observed when high concentrations of Fe(2+), Fe(3+) and Ca(2+) existed. The optimal decolorising conditions obtained from Taguchi design were as follows: temperature 37˚C, pH 7.0, Fe(3+) and proline concentrations of 7 mM and 3.0 g/L, respectively. Under the optimal conditions, 94.5% of Acid Black 172 (100 mg/L) could be decolorised by the strain in 24 h. The kinetics of the decolorisation best fitted the first order kinetic model (R(2)=0.981). Besides, the phytotoxicity study demonstrated a good detoxification by the strain. This work has a certain practical value in microbial decolorisation of textile wastewater.
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10.2166/wst.2011.328
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28251321
|
Comparing the effects of peritonsillar infiltration of tramadol before and after the surgery on post-tonsillectomy pain.
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The aim of the study was to compare the effects of peritonsillar infiltration of tramadol before and after the surgery on post-tonsillectomy pain. In this double-blinded clinical trial study, 80 children aged 5-12 years old with ASA (American Society of Anesthesiologists) class I or II undergoing tonsillectomy involved. In group A (n = 40), after anesthesia induction and before starting the surgery, tramadol 2 mg/kg diluted in normal saline up to 2 cc total volume was injected into the tensile bed by the anesthesiologist using a 25 gauge needle. Surgery began 3 min later and the tonsils were removed using the sharp dissection method. In children of group B (n = 40), anesthesia induction was performed. When surgery was completed, tramadol 2 mg/kg diluted in normal saline up to 2 cc total volume was injected at the site of removing each tonsil using a 25 gauge needle by the anesthesiologist. Using the CHEOPS (Children's Hospital of Eastern Ontario Pain Scale) Scale, pain recorded at different times. Patient sedation was recorded using the RAMSAY Sedation Scale. All the data were analyzed using SPSS 17 statistical software. Two groups significantly felt different pain intensities at different times following the surgery. At the three times, the mean sedation score in the group receiving tramadol infiltration before surgery was a little higher compared to the other group, but this difference was not significant (p > 0.05). As for the relative frequency of nausea and vomiting, the difference was not significant (p = 0.793). Request for analgesics between the groups was not significant (p = 0.556). The mean time of the first feeding after the surgery was not significant between the groups (p = 0.062). Surgical duration was almost the same for both groups (p > 0.05). Systolic blood pressures (before surgery, before extubation, and after extubation) were statistically the same in both groups (p < 0.05). Furthermore, systolic blood pressures 10, 15, and 30 min after entry into the recovery room were the same in both groups. We concluded that peritonsillar infiltration of tramadol before surgery controlled postoperative pain better from 8 h after the surgery to hospital discharge (late effect), but that local infiltration of tramadol after surgery controlled postoperative pain better up to 2 h after the operation (early effect).
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10.1007/s00405-017-4477-z
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25295133
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Cost-effectiveness analysis reveals microsurgical varicocele repair is superior to percutaneous embolization in the treatment of male infertility.
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Varicoceles are a common cause of male infertility; repair can be accomplished using either surgical or radiological means. We compare the cost-effectiveness of the gold standard, the microsurgical varicocele repair (MV), to the options of a nonmicrosurgical approach (NMV) and percutaneous embolization (PE) to manage varicocele-associated infertility. A Markov decision-analysis model was developed to estimate costs and pregnancy rates. Within the model, recurrences following MV and NMV were re-treated with PE and recurrences following PE were treated with repeat PE, MV or NMV. Pregnancy and recurrence rates were based on the literature, while costs were obtained from institutional and government supplied data. Univariate and probabilistic sensitivity-analyses were performed to determine the effects of the various parameters on model outcomes. Primary treatment with MV was the most cost-effective strategy at $5402 CAD (Canadian)/pregnancy. Primary treatment with NMV was the least costly approach, but it also yielded the fewest pregnancies. Primary treatment with PE was the least cost-effective strategy costing about $7300 CAD/pregnancy. Probabilistic sensitivity analysis reinforced MV as the most cost-effective strategy at a willingness-to-pay threshold of >$4100 CAD/pregnancy. MV yielded the most pregnancies at acceptable levels of incremental costs. As such, it is the preferred primary treatment strategy for varicocele-associated infertility. Treatment with PE was the least cost-effective approach and, as such, is best used only in cases of surgical failure.
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10.5489/cuaj.1873
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20078655
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Single-cell gene profiling of planarian stem cells using fluorescent activated cell sorting and its "index sorting" function for stem cell research.
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To achieve an integrated understanding of the stem cell system of planarians at both the cellular and molecular levels, we developed a new method by combining "fluorescent activated cell sorting (FACS) index sorting" analysis and single-cell reverse transcription-polymerase chain reaction (RT-PCR) to detect the gene expression and cell cycle state of stem cells simultaneously. Single cells were collected using FACS, and cDNAs of each cell were used for semi-quantitative RT-PCR. The results were plotted on the FACS sorting profile using the "index sorting" function, which enabled us to analyze the gene expression in combination with cell biological data (such as cell cycle phase) for each cell. Here we investigated the adult stem cells of planarians using this method and obtained findings suggesting that the stem cells might undergo commitment during S to G2/M phase. This method could be a powerful and straightforward tool for examining the stem cell biology of not only planarians but also other organisms, including vertebrates.
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10.1111/j.1440-169X.2009.01157.x
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10411440
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Should carcinoembryonic antigen be used in the management of patients with colorectal cancer?
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The contribution of carcinoembryonic antigen carcinoembryionic antigen for the effective management of colorectal cancer patients remains a controversial issue. The aim of this study is to attempt to get some valid answers to its function in the diagnosis, prognosis, and overall management of colorectal cancer patients. A retrospective review of colorectal cancer patients managed and prospectively registered by the authors between 1985 and 1998 was performed. Serum carcinoembryionic antigen levels were determined preoperatively in 209 patients with primary colorectal cancer and postoperatively in 196 patients who had undergone curative resection of their tumors, according to a fixed schedule. A maximum value of 5 ng/ml was accepted as being normal. With the exception of endoscopy, all other diagnostic techniques were only used after an abnormal carcinoembryionic antigen result (a raised value found twice consecutively). carcinoembryionic antigen preoperative values were raised only in 40 percent of patients and were related to disease stage, with the highest values found in patients with Stage IV disease. However, an elevated preoperative carcinoembryionic antigen value had a very marked prognostic importance, with a statistically significant difference in survival curves (Kaplan-Meier); the same was valid for curatively resected patients (Stages I, II, and III) and for Stages II and III patients considered separately. Multivariate analysis using the Cox proportional hazards technique confirmed these results, showing preoperative carcinoembryionic antigen to have an independent prognostic value, with a relative risk of recurrence of 3.74 for patients with raised preoperative carcinoembryonic antigen levels. In postoperative follow-up, carcinoembryionic antigen elevation was found to be a very accurate marker of recurrence (sensitivity, 77 percent; specificity, 98 percent), mainly in liver metastasis (sensitivity, 100 percent), and the best marker of asymptomatic recurrence (63 percent of cases). However, carcinoembryionic antigen's impact on overall survival was negligible because of the poor results of surgical treatment of recurrences. Preoperative carcinoembryionic antigen is a very important prognostic indicator and should be considered in future trials. Postoperative carcinoembryionic antigen elevation is a very sensitive marker of recurrence and even of asymptomatic recurrence, but its impact on overall survival does not seem to be relevant. Nevertheless, carcinoembryionic antigen should continue to be used in colorectal cancer patients until better methods of diagnosis and treatment of recurrence are developed.
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10.1007/BF02237104
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17522237
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Sentinel lymph node biopsy in male patients with early breast cancer.
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Mastectomy with axillary dissection is still the most commonly recommended procedure for male breast cancer. The aim of this study was to retrospectively evaluate our experience in 32 male patients with early breast cancer who underwent sentinel lymph node biopsy (SLNB) and axillary dissection only in cases of metastases in the sentinel lymph node (SLN). The median age was 58 years (range, 33-80). Lymphoscintigraphy was successful in all patients, with a mean number of visualized SLNs per patient of 1.3 (range, 1-2). At surgery, the identification rate of the SLN was 100%, with a mean number of removed SLNs per patient of 1.5 (range, 1-3). Twenty-six patients had negative SLNs, six patients had positive SLNs. Two patients with metastatic SLNs had additional positive nodes. After a median follow-up of 30 months (range, 1-63) no axillary reappearance of the disease occurred. As with women, we recommend SLNB in male patients with breast cancer and clinically negative axilla.
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10.1634/theoncologist.12-5-512
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34074321
|
Thrombosis and bleeding outcomes in the treatment of cerebral venous thrombosis in cancer.
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There is a need for clinical outcome data of cerebral venous thrombosis (CVT) in cancer patients. We examined the recanalization, thrombosis recurrence and major bleeding during CVT treatment in a cancer exclusive adult population. We performed a retrospective review of cancer associated CVT identified through an institutional data warehouse. The primary endpoint was radiological and comprised the evaluation of thrombus recanalization at 12 months. Secondary endpoints were clinical and included rates of bleeding complications and recurrence of CVT. Variables were compared across subgroups of study outcomes. The backward stepdown procedure was used to identify variables for the final logistic model regarding thrombosis and bleeding outcomes. The population included forty-five patients, slightly predominant of male adults (55.6%) with a median age of 54.5 years. Solid malignancies comprised 64.4% of cases. A total of 31 cases were treated with anticoagulation. CVT recanalization was documented in almost 60% of cases. The cerebral venous thrombosis recurrence or propagation rate at 12 months was 15.6%. Major bleeding complications were observed in 15 patients. Our findings are suggestive of a narrow therapeutic index of anticoagulation in cancer-CVT. Careful monitoring of anticoagulation effect and bleeding complications are of utmost clinical relevance in cancer patients. Further larger and controlled studies are needed to confirm our observations.
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10.1186/s12959-021-00292-9
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38590770
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Cardiac biomarkers and left ventricular systolic function in former very preterm infants and term controls at preschool age.
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Due to improvements in perinatal care, survival rates of preterm infants have improved during the last decades. However, these infants remain at risk of developing cardiovascular sequelae later in life. This study aimed to investigate the cardiac biomarkers and left ventricular systolic function in former preterm infants in comparison with term controls at preschool age. The study included children aged 5-7 years old born below 32 weeks of gestational age. The control group consisted of same-age children born at term. Basic data of study participants were collected using questionnaires and follow-up databases. During the study visit, we recorded anthropometric data and blood pressure readings, determined high-sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentrations, and calculated fractional shortening (FS) and left ventricular mass (LVM). Term-born ( n = 25; median gestational age, 40.1 weeks) compared with preterm-born infants ( n = 80; median gestational age 29.6 weeks) showed no significant differences in the median concentration of hs-cTnT [median, 3.5 (IQR 3.5; 3.5) vs. 3.5 (3.5; 3.5) ng/L, p = 0.328] and the median concentration of NT-pro-BNP [median, 91.0 (IQR 40.8; 150.3) vs. 87.5 (50.1; 189.5) ng/L, p = 0.087]. FS and LVM/LVMI were not significantly different between the two groups. At preschool age, we observed no significant differences in cardiac biomarkers and left ventricular systolic function in preterm infants. Further studies are warranted to explore the potential of cardiac biomarkers as a prognostic tool for subclinical cardiac alterations after preterm birth. © 2024 Höck, Posod, Odri Komazec, Griesmaier, Ralser, Pupp-Peglow and Kiechl-Kohlendorfer.
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10.3389/fped.2024.1376360
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12150202
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Doxorubicin directly binds to the cardiac-type ryanodine receptor.
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The clinical use of doxorubicin, an antineoplasmic agent, is limited by its extensive cardiotoxicity which is mediated by the mobilization of intracellular Ca2+ from SR. In order to elucidate the mechanism of Ca2+ release, we analyzed the binding sites of doxorubicin on rabbit cardiac SR (sarcoplasmic reticulum). One of the binding sites was identified as cardiac-type ryanodine receptor (RyR2) which was purified by immunoprecipitation from solubilized cardiac SR in the presence of DTT. Ligand blot analysis revealed the direct binding of doxorubicin to RyR2. The binding of doxorubicin to RyR2 was specific and displaced by caffeine. Both doxorubicin and caffeine enhanced [3H]-ryanodine binding to RyR2 in a Ca2+ dependent manner. These results suggest that there is a doxorubicin binding site on RyR2.
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10.1016/s0024-3205(02)01524-2
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28719312
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Molecular Epidemiology of Malaria in Cameroon and Côte d'Ivoire. XXXI. Kelch 13 Propeller Sequences in Plasmodium falciparum Isolates before and after Implementation of Artemisinin-Based Combination Therapy.
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Artemisinin-resistant malaria has not been reported from Africa, but resistance can possibly spread from Asia or arise independently in Africa. The emergence of artemisinin resistance in Africa can be monitored by molecular assay of Kelch 13 (K13) propeller sequences. A total of 251 archived DNA samples of Plasmodium falciparum isolates collected in 2002, 2003, and 2006 in Yaounde, Cameroon, and 47 samples collected in 2006 and 2013 in Abidjan, Côte d'Ivoire, were analyzed for K13-propeller sequence polymorphism. Only one isolate carried a mutant K13-propeller allele (E602D). None of the isolates carried the key mutant alleles (Y493H, R539T, I543T, and C580Y) associated with artemisinin resistance in Cambodia. The presence of the mutant allele was not correlated with in vitro response to dihydroartemisinin determined by the classical hypoxanthine incorporation assay. There was no evidence of K13 mutations associated with artemisinin resistance before and soon after the introduction of artemisinin-based combination therapies in Cameroon and Côte d'Ivoire.
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10.4269/ajtmh.16-0889
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36525295
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A Membrane-Embedded Macromolecular Catalyst with Substrate Selectivity in Live Cells.
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Substrate selectivity is one of the most attractive features of natural enzymes from their "bind-to-catalyze" working flow and is thus a goal for the development of synthetic enzyme mimics that mediate abiotic transformations. However, despite the recent success in the preparation of substrate-selective enzyme mimics based on single-chain nanoparticles, examples extending such selectivity into living systems have been absent. In this article, we report the in cellulo substrate selectivity of an enzyme-mimicking macromolecular catalyst based on a cationic dense-shell nanoparticle (DSNP) scaffold. With a systematic study on DSNP's structure-activity relationship, we demonstrate that the DSNP has excellent membrane affinity that is governed by several contributing factors, namely, charge density, type of charge, and particle size, and the best-performing phosphonium-rich DSNP can be used as a membrane-embedded catalyst (MEC) for efficient on-membrane synthesis. Importantly, the DSNP catalyst retains its selectivity toward lipophilic and anionic substrates when working as an MEC for on-membrane ligation. The usefulness of such substrate selectivity and on-membrane catalysis strategy was exemplified with several molecules of interest with low cell permeability and anionic nature, which were successfully transported into eukaryotic cells by after their formation directly on the cell membrane.
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10.1021/jacs.2c11168
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33484303
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The effect of bicipital groove morphology on the stability of the biceps long head tendon.
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Long head of biceps tendon (LHBT) instability is an important source of pain and disability for the shoulder. Supraspinatus and subscapularis tendons contribute to the formation of the biceps pulley system, which maintains biceps stability during shoulder movements. The aim of this study is to evaluate the effect of morphology of bicipital groove on the stability of LHBT. Also, to evaluate the relationship between bicipital groove morphology and subscapularis rupture and supraspinatus rupture. Surgical images and magnetic resonance images of 200 patients who underwent shoulder arthroscopy surgery in our clinic between January 2016 and December 2017 were retrospectively analyzed. The depth of groove, medial wall angle and opening angle values of 200 patients were measured on MRI. The stability of the biceps long head tendon, rotator cuff tear and SLAP lesions was recorded by monitoring the shoulder arthroscopy records in each groups. There were 200 patients, 131 male and 69 female, with an average age of 40.9 ± 14.2 (range: 17.0-79.0) years. In 69 (34.5%) patients, long head of the biceps tendon (LHBT) instability was detected. The patients were divided into two groups according to LHBT instability. The subscapularis rupture was significantly more frequent in the group with LHBT instability (52.2%) than the group without LHBT instability (4.6%) (p < 0.001). The supraspinatus tear was observed in 72.5% in the group with instability and 56.5% in the non-instability group, which shows a statistical difference between the two groups (p = 0.027). The presence of SLAP was observed in similar rates in both groups (p = 0.053). Mean depth of groove, medial wall angle, and opening angle measurements were similar in both groups (p = 0.568, p = 0.393 and p = 0.598, respectively). To conclude, the morphology of the bicipital groove is not related to the stability of LHBT, and the soft tissue factors above the bicipital groove rather than bone morphology are important in stability. In addition, subscapularis rupture is a pre-disposing factor for LHBT instability; therefore, we recommend a more careful examination of LHBT in patients with subscapularis rupture. III. © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
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10.1007/s00402-021-03760-z
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14657277
|
RNA interference of valosin-containing protein (VCP/p97) reveals multiple cellular roles linked to ubiquitin/proteasome-dependent proteolysis.
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We have used RNA interference (RNAi) to examine the functional relationship between valosin-containing protein (VCP/p97/Cdc48p/TER94) ATPase and the ubiquitin-proteasome system (UPS) in Drosophila S2 and human HeLa cells. In both cell types, RNAi of VCP (and, to a lesser extent, of certain VCP-interacting proteins) caused significant accumulation of high-molecular-weight conjugates of ubiquitin, an indication of inhibited UPS function. However, decreased VCP levels did not directly inhibit proteasome activity. In HeLa cells, polyubiquitinated proteins accumulated as dispersed aggregates rather than as single aggresomes, even in the presence of proteasome inhibitors, which normally promote aggresome formation. RNAi of VCP caused extensive vacuolization of the cytoplasm, and proteasome inhibitors exaggerated this feature. RNAi of VCP had little effect on S2 cell proliferation but blocked cell-cycle progression and induced mitotic abnormalities and apoptosis in HeLa cells. These results indicate that VCP plays an important general role in mediating the function of the UPS, probably by interacting with potential proteasome substrates before they are degraded by the proteasome.
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10.1242/jcs.00841
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7049581
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A method for the intraocular injection of micro-volumes in small animal species.
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A method has been developed for the intraocular administration of small volumes (0.5-1.5 microliters) in small animal species such as guniea pigs and rats. The method was found to yield reproducible injection volumes and resulted in minimal ocular trauma. The aqueous humor of eyes injected with saline contained normal levels of protein and was free of white blood cells. Responses to Prostaglandin E2 and E. Coli endotoxin were dose-dependent and as expected.
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10.3109/02713688109001873
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21292591
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Representing cardiac bidomain bath-loading effects by an augmented monodomain approach: application to complex ventricular models.
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Although the cardiac bidomain model has been widely used in the simulation of electrical activation, its relatively computationally expensive nature means that monodomain approaches are generally required for long-duration simulations (for example, investigations of arrhythmia mechanisms). However, the presence of a conducting bath surrounding the tissue is known to induce wavefront curvature (surface leading bulk), a phenomena absent in standard monodomain approaches. Here, we investigate the biophysical origin of the bidomain bath-loading induced wavefront curvature and present a novel augmented monodomain-equivalent bidomain approach faithfully replicating all aspects of bidomain wavefront morphology and conduction velocity, but with a fraction of the computational cost. Bath-loading effects are shown to be highly dependent upon specific conductivity parameters, but less dependent upon the thickness or conductivity of the surrounding bath, with even relatively thin surrounding fluid layers (~ 0.1 mm) producing significant wavefront curvature in bidomain simulations. We demonstrate that our augmented monodomain approach can be easily adapted for different conductivity sets and applied to anatomically complex models, thus facilitating fast and accurate simulation of cardiac wavefront dynamics during long-duration simulations, further aiding the faithful comparison of simulations with experiments.
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10.1109/TBME.2010.2096425
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24309103
|
EpCAM expression in the prostate cancer makes the difference in the response to growth factors.
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Epithelial cell adhesion molecule (EpCAM) is expressed in tumors with an epithelial cell of origin, in a heterogeneous manner. Prostate cancer stem-like cells highly express EpCAM. However, little is known about how EpCAM is involved in the ability of cells to adapt to micro-environmental changes in available growth factors, which is one of the essential biological phenotypes of cancer stem-like cells (CSCs). EpCAM-high and EpCAM-low subpopulations of cells were established from the prostate cancer cell line PC-3. Signal transductions in response to serum starvation, and on the exposure to EGF ligand or the specific inhibitor were analyzed in terms. Furthermore, we analyzed the expression level of amino acid transporters which contribute to the activation of mTOR signal between the two subgroups. EpCAM-high and EpCAM-low PC-3 subpopulations showed markedly different responses to serum starvation. EpCAM expression was positively correlated with activation of the mTOR and epithelial growth factor receptor (EGFR) signaling pathways. Furthermore, AMP-activated protein kinase (AMPK) was gradually de-activated in EpCAM-low PC-3 cells in the absence of serum. EpCAM regulates the AMPK signaling pathway, essential for the response to growth factors characterized by EGF. LAT1, the amino acid transporter stabilized at the cellular membrane by EpCAM, is likely to be responsible for the difference in the susceptibility to EGF between EpCAM-high and EpCAM-low PC-3 cells. Copyright © 2013 Elsevier Inc. All rights reserved.
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10.1016/j.bbrc.2013.11.093
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21914470
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Encapsulation of the flavonoid quercetin with an arsenic chelator into nanocapsules enables the simultaneous delivery of hydrophobic and hydrophilic drugs with a synergistic effect against chronic arsenic accumulation and oxidative stress.
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Chronic arsenic exposure causes oxidative stress and mitochondrial dysfunction in the liver and brain. The ideal treatment would be to chelate arsenic and prevent oxidative stress. meso-2,3-Dimercaptosuccinic acid (DMSA) is used to chelate arsenic but its hydrophilicity makes it membrane-impermeative. Conversely, quercetin (QC) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, and it is not possible to solubilize these two compounds in a single nontoxic solvent. Nanocapsules have emerged as a potent drug delivery system and make it feasible to incorporate both hydrophilic and lipophilic compounds. Nanoencapsulated formulations with QC and DMSA either alone or coencapsulated in polylactide-co-glycolide [N(QC+DMSA)] were synthesized to explore their therapeutic application in a rat model of chronic arsenic toxicity. These treatments were compared to administration of quercetin or DMSA alone using conventional delivery methods. Both nanoencapsulated quercetin and nanoencapsulated DMSA were more effective at decreasing oxidative injury in liver or brain compared to conventional delivery methods, but coencapsulation of quercetin and DMSA into nanoparticles had a marked synergistic effect, decreasing liver and brain arsenic levels from 9.5 and 4.8μg/g to 2.2 and 1.5μg/g, respectively. Likewise, administration of coencapsulated quercetin and DMSA virtually normalized changes in mitochondrial function, formation of reactive oxygen species, and liver injury. We conclude that coencapsulation of quercetin and DMSA may provide a more effective therapeutic strategy in the management of arsenic toxicity and also presents a novel way of combining hydrophilic and hydrophobic drugs into a single delivery system. Copyright © 2011. Published by Elsevier Inc.
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10.1016/j.freeradbiomed.2011.08.019
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38995470
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The potential application of Czenspinskia transversostriata in biological control.
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Phytoseiid predatory mites are one of the most important groups of biocontrol agents, commonly used in biological control. The ability to produce these predatory mites economically, at high density on cheap factitious food sources, is a major contributor to their success. Astigmatid mites are the most widely used factitious food for this purpose. In this study, we investigated the potential application of the leaf-dwelling astigmatid mite Czenspinskia transversostriata (Oudemans) (Acari: Winterschmidtiidae) as a prey mite in biological control. We tested whether C. transversostriata is a suitable food source for the predatory mite Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae), both in the laboratory and on cucumber plants. Based on a reproduction trial, C. transversostriata proved to be an equally good food source compared to both pollen of Typha angustifolia L. (Poales: Typhaceae) and a frequently used prey mite Carpoglyphus lactis L. (Acari: Carpoglyphidae). In a pre-establishment trial on cucumber plants, populations of A. swirskii reached equally high densities when supplemented with C. transversostriata, compared to C. lactis. Lastly, we show that C. transversostriata is capable of feeding and reproducing on powdery mildew growing on cucumber plants, thereby slowing down the development of the pathogenic fungus. Results derived from this study show that C. transversostriata may have multiple potential applications in biological control programs. © 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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10.1007/s10493-024-00945-0
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21453946
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Genetic diversity of porcine circovirus type 2 (PCV2) in the Romanian wild boar population.
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In this study, we have analyzed 23 PCV2 ORF2 sequences recovered from wild boar population in Romania. The PCV2 sequences were originated from different geographical regions in Romania, and collected between 2008 and 2009 during the classical swine fever virus (CSFV) surveillance campaign. Complete open reading frame 2 (ORF2) nucleotide sequences were obtained and compared with sequences mainly from European and Asian isolates. The Romanian sequences were identified as belonging to previously described clusters 2a and 2b, with high degree of heterogeneity (PCV2 ORF2 nucleotide homology ranged between 90.1% and 100%). Interestingly, for cluster 2a, the majority of the sequences (8 from a total number of 9) clustered mainly with the Asian isolates (especially China, but also India and South Korea), with three exceptions from Europe previously reported in Germany, Belgium and The Netherlands. Copyright © 2011 Elsevier Ltd. All rights reserved.
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10.1016/j.rvsc.2011.03.002
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23724387
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Septic embolism in the intensive care unit.
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Septic embolism encompasses a wide range of presentations and clinical considerations. From asymptomatic, incidental finding on advanced imaging to devastating cardiovascular or cerebral events, this important clinico-pathologic entity continues to affect critically ill patients. Septic emboli are challenging because they represent two insults-the early embolic/ischemic insult due to vascular occlusion and the infectious insult from a deep-seated nidus of infection frequently not amenable to adequate source control. Mycotic aneurysms and intravascular or end-organ abscesses can occur. The diagnosis of septic embolism should be considered in any patient with certain risk factors including bacterial endocarditis or infected intravascular devices. Treatment consists of long-term antibiotics and source control when possible. This manuscript provides a much-needed synopsis of the different forms and clinical presentations of septic embolism, basic diagnostic considerations, general clinical approaches, and an overview of potential complications.
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10.4103/2229-5151.109423
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36907203
|
Music Perception Abilities of the Hearing Amplification System Users.
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Recently, the improvement of music perception abilities for emotional stability and high quality of life has become important for the hearing loss group. This study aimed to examine and compare the music perception abilities of the normal hearing (NH) and hearing amplification system (HAS) groups to find the needs and methods of music rehabilitation. Subjects and. The data were collected from 15 NH adults (33.1±11.4 years) and 15 HAS adults (38.7±13.4 years), of whom eight wore cochlear implant [CI] systems and seven wore CI and hearing aid systems depending on pitch, melody, rhythm, timbre, emotional reaction, and harmony perception tests. A mismatch negativity test was also conducted, and attitudes toward and satisfaction with listening to music were measured. The correction percentages for the NH and HAS groups were 94.0%±6.1% and 75.3%±23.2% in the pitch test; 94.0%±7.1% and 30.3%±25.9% in the melody test; 99.3%±1.8% and 94.0%± 7.6% in the rhythm test; 78.9%±41.8% and 64.4%±48.9% in the timbre test; 96.7%±10.4% and 81.7%±16.3% in the emotional reaction test; and 85.7%±14.1% and 58.4%±13.9% in the harmony test, respectively, showing statistical significance (p<0.05). For the mismatch negativity test, the area of the waveform was smaller in the HAS groups than in the NH groups, with 70 dB of stimulation showing no statistical significance. The response rates for satisfaction with listening to music were 80% and 93.3% for the NH and HAS groups, showing no statistical significance. Although the HAS group showed lower music perception ability than the NH group overall, they showed a strong desire for music listening. Also, the HAS group revealed a higher degree of satisfaction even when listening to unfamiliar music played with unusual instruments. It is suggested that systematic and constant musical rehabilitation based on musical elements and different listening experiences will improve music perception qualities and abilities for HAS users.
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10.7874/jao.2022.00367
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8959316
|
Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women.
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Several epidemiological studies have identified an association between nonsteroidal anti-inflammatory drug (NSAID) use and colorectal cancer risk in women. We examined this association in a population-based case-control study in Wisconsin women. Between 1991 and 1992, 184 women ages 40-74 years with colorectal cancer were identified through the statewide cancer registry and 293 population-based control women were randomly selected via telephone. Regular NSAID use was defined as at least twice weekly for 12 months or longer. After adjusting the data for age, controls were more likely than cases to report regular NSAID use (38 versus 27%). Following adjustment for age, prior sigmoidoscopy use, family history of large bowel cancer, and body mass index, women who regularly used NSAIDs were approximately one-third less likely to be diagnosed with colorectal cancer compared to women who did not use NSAIDs [odds ratio (OR), 0.65; 95% confidence interval (CI), 0.40-1.03]. A statistically significant effect of duration of use was identified, although the ORs did not show a consistent trend. No significant effect of frequency of NSAID use was observed. When the type of NSAID used was examined (aspirin or nonaspirin), subjects who used nonaspirin compounds had a statistically significantly lower risk of colorectal cancer (OR, 0.43; 95% CI, 0.20-0.89), compared to nonusers, whereas aspirin users had only a small, nonsignificant reduction in cancer risk (OR, 0.79; 95% CI, 0.46-1.36). These data add support to the hypothesis that regular NSAID use is associated with lower colorectal cancer risk in women and suggest that the type of NSAID used may be important.
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8417938
|
Use of maximum expiratory flow-volume curve parameters in the assessment of exercise-induced bronchospasm.
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Exercise-induced bronchospasm (EIB) is often inferred from the reduction after exercise in one arbitrarily selected value derived from the maximum expiratory flow-volume (MEFV) curve (eg, FEV1) on a single test; however, patients with symptoms of EIB not meeting these criteria may risk being undiagnosed. To assess the ability of repeated tests using additional MEFV parameters in identifying EIB-prone patients, we investigated the effects of exercise provocation on the MEFV curve on two separate occasions. Of 95 patients with symptoms of EIB, 61 had reproducible exercise-induced changes (< 10 percent intraresponse variation), falling into four patterns: 27 (44 percent) had significantly reduced VC and airflow throughout the MEFV curve; 18 (30 percent) had unchanged VC but decreased airflow throughout the curve; 11 (18 percent) had reduced airflow above 50 percent VC but not below 50 percent VC; and 5 (8 percent) had significant reductions in airflow only at 50 percent VC or below. Of the other 34 subjects, 18 had no apparent response, and 16 responded on only one occasion, making objective assessment of these patients' EIB equivocal. We conclude that for a given individual, failure to meet arbitrary criteria does not rule out EIB. Additionally, a more subjective approach that integrates, among other factors, all routine MEFV curve parameters taken from multiple tests with clinical symptoms and history provide a more accurate assessment of EIB.
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10.1378/chest.103.1.64
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29126816
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Effects of spermine and the passive avoidance learning (PAL) following cerebral ischemia in chicks: Association with neuroprotection of pyramidal cells.
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The aim of this study is to investigate the effects of spermine and the passive avoidance learning on hippocampus following transient cerebral ischemia in the chicks. The study is composed of the pure control (CG), sham (SG) and experimental groups (n=20). Experimental groups (ischemia group, IG and ischemia-spermine group, ISG) were exposed to ischemia for 20min whereas the SG was exposed to sham operation and CG group was not exposed to any operation. Passive avoidance learning (PAL) was applied to the half number of the subjects in each group. Both before and after 7days from the ischemia, operated animals were taken to PAL and then they were sacrificed. Total numbers of neurons in the hippocampus were stereologically estimated using Cresyl violet stained sections. We detected that number of neurons was increased following PAL and especially spermine treatment. According to our results, we suggested that spermine may reduce the deleterious effects of the ischemia by causing to increase in the neuronal number and so, it may be slightly supportive to the PAL. Copyright © 2017 Elsevier B. V. All rights reserved.
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10.1016/j.jchemneu.2017.11.006
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25647891
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Taking a fresh look at Medicaid.
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Hospitals should evaluate four approaches to providing high-quality, cost-effective care for Medicaid patients: Continue to focus on strengthening primary care and improving cost efficiency in the current Medicaid market. Develop value-based, risk-sharing contracts with existing Medicaid managed care organizations. Partner with existing Medicaid managed care organizations to develop new products for targeted market segments. Own a health plan targeting the Medicaid market segment.
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36840100
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The Potential of Cover Crops for Weed Management: A Sole Tool or Component of an Integrated Weed Management System?
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Cover crops are an important component of integrated weed management programs in annual and perennial cropping systems because of their weed suppressive abilities. They influence weed populations using different mechanisms of plant interaction which can be facilitative or suppressive. However, the question often arises if cover crops can be solely relied upon for weed management or not. In this review we have tried to provide examples to answer this question. The most common methods of weed suppression by an actively growing cover crop include competition for limited plant growth resources that result in reduced weed biomass, seed production, and hence reductions in the addition of seeds to the soil seedbank. Cover crop mulches suppress weeds by reducing weed seedling emergence through allelopathic effects or physical effects of shading. However, there is a great degree of variability in the success or failure of cover crops in suppressing weeds that are influenced by the cover crop species, time of planting, cover crop densities and biomass, time of cover crop termination, the cash crop following in the rotation, and the season associated with several climatic variables. Several studies demonstrated that planting date was important to achieve maximum cover crop biomass, and a mixture of cover crop species was better than single cover crop species to achieve good weed suppression. Most of the studies that have demonstrated success in weed suppression have only shown partial success and not total success in weed suppression. Therefore, cover crops as a sole tool may not be sufficient to reduce weeds and need to be supplemented with other weed management tools. Nevertheless, cover crops are an important component of the toolbox for integrated weed management.
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10.3390/plants12040752
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36702015
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Human papillomavirus status and prognosis of oropharyngeal high-grade neuroendocrine carcinoma.
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The prognostic impact of human papillomavirus (HPV) infection or smoking on oropharyngeal high-grade neuroendocrine carcinoma (HG-NEC) is not established. Retrospective study with patients with oropharyngeal HG-NEC seen at MD Anderson Cancer Center from 1997 to 2020, and previously reported patients with oropharyngeal HG-NEC and known p16 and HPV status from the literature review. Survival was estimated with the Kaplan-Meier method, and survival differences assessed with the log-rank test and Cox proportional hazards models. Thirty patients were included; most had a heavy (≥10 pack-years) smoking history (52%), locoregional disease (stage III-IVB; 77%), and p16-positive tumor (92%). HPV was positive in 65% of tested samples (15/23). Of 24 patients treated with curative intent, the objective response rates was 90% (9/10) and 81% (17/21), respectively, for induction chemotherapy and definitive radiotherapy. During follow-up, 54% (13/24) recurred, mostly (11/13) at distant sites. Median overall survival (OS) was 46 months (95% CI, 14.3 - NA). OS was not associated with HPV status (HR 0.73, P = 0.6) or smoking (HR 1.16, P = 0.8). Among 63 patients with known HPV status after the literature review (19 HPV- and 44 HPV + ), HPV status remained unassociated with OS (P = 0.92). This is the largest retrospective cohort of oropharyngeal HG-NEC. Distant recurrence rate after curative treatment was high, suggesting that multimodality treatment including systemic therapy may benefit patients with locally advanced disease. HPV infection did not affect survival outcomes, therefore should not lead to therapy de-intensification for this histology. Copyright © 2023 Elsevier Ltd. All rights reserved.
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10.1016/j.oraloncology.2023.106311
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1000898
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The radiology of the intrauterine contraceptive device.
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Some intrauterine devices are of low radiographic density and require careful technique for their demonstration. The main indications for radiology are to exclude deformity, which reduces the loop's efficiency, perforation of the uterus, or expulsion of the loop.
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10.1016/s0009-9260(76)80124-9
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24436739
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Innovative intraoperative titanium mesh preparation for safer implantation.
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Titanium meshes have been extensively used in craniomaxillofacial surgery. The benefits of these titanium implants include being inert, stable, and radiopaque and having good drainage properties. The titanium mesh is cut to shape and bent before implantation, which may give rise to the cut edges being jagged and sharp. This can lead to soft tissue being caught or lacerated by these sharp ends. A change in technique to cut and shape the implant may reduce this problem. The implant should be cut right at the end of the bars flush with the remaining parts of the implant. We present a new and simple method for smoothing these troublesome edges. We use the diathermy scratch pad or tip cleaner, a tool used frequently in every major surgery. This scratch pad can be used as a rasp to smoothen the edges of the titanium mesh once it is cut into shape.
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10.1055/s-0032-1329544
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33436515
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Complementary Roles of Wood-Inhabiting Fungi and Bacteria Facilitate Deadwood Decomposition.
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Forests accumulate and store large amounts of carbon (C), and a substantial fraction of this stock is contained in deadwood. This transient pool is subject to decomposition by deadwood-associated organisms, and in this process it contributes to CO 2 emissions. Although fungi and bacteria are known to colonize deadwood, little is known about the microbial processes that mediate carbon and nitrogen (N) cycling in deadwood. In this study, using a combination of metagenomics, metatranscriptomics, and nutrient flux measurements, we demonstrate that the decomposition of deadwood reflects the complementary roles played by fungi and bacteria. Fungi were found to dominate the decomposition of deadwood and particularly its recalcitrant fractions, while several bacterial taxa participate in N accumulation in deadwood through N fixation, being dependent on fungal activity with respect to deadwood colonization and C supply. Conversely, bacterial N fixation helps to decrease the constraints of deadwood decomposition for fungi. Both the CO 2 efflux and N accumulation that are a result of a joint action of deadwood bacteria and fungi may be significant for nutrient cycling at ecosystem levels. Especially in boreal forests with low N stocks, deadwood retention may help to improve the nutritional status and fertility of soils. IMPORTANCE Wood represents a globally important stock of C, and its mineralization importantly contributes to the global C cycle. Microorganisms play a key role in deadwood decomposition, since they possess enzymatic tools for the degradation of recalcitrant plant polymers. The present paradigm is that fungi accomplish degradation while commensalist bacteria exploit the products of fungal extracellular enzymatic cleavage, but this assumption was never backed by the analysis of microbial roles in deadwood. This study clearly identifies the roles of fungi and bacteria in the microbiome and demonstrates the importance of bacteria and their N fixation for the nutrient balance in deadwood as well as fluxes at the ecosystem level. Deadwood decomposition is shown as a process where fungi and bacteria play defined, complementary roles. Copyright © 2021 Tláskal et al.
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10.1128/mSystems.01078-20
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39572652
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Evaluation of radiological hazards associated with some Egyptian marble and granite rocks.
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The aim of the current study is to evaluate the radioactivity estimate the radiological risk of some granites and marbles rocks and explaining the cause of increased radioactivity in some types of rocks. The radioactivity of some granites and marbles produced in Egypt were determined by using a Germanium detector. Three types of marble (Breshia, Galala, and Trista) and three types of granite (Gandola, White Halayeb, and Red Aswani) were collected. All marble samples show low radioactivity with average activity concentrations of 20 ± 2, 4.50 ± 0.5, and 6.70 ± 1.2 Bqkg - 1 for 226 Ra, 232 Th, and 40 K respectively. Granite samples have higher activity concentration with averages of 152 ± 7, 129 ± 8, and 1228 ± 15 Bqkg - 1 for 226 Ra, 232 Th, and 40 K respectively which exceed the world average values of soil (32,45,412 Bqkg - 1 for 226 Ra, 232 Th, and 40 K respectively) excluding Granite G.2 (white Halayeb) as it shows an insignificant level of radioactivity. The annual effective doses of marble samples Breshia, Galala, and Trista were measured to be 4.42 ± 0.4; 158 ± 14 and 153 ± 15 µSvy - 1, and 1008 ± 147, 80 ± 7 and 987 ± 45.0 µSvy - 1 for the granite samples Gandola, White Halayeb and Red Aswani respectively. The radiation hazard parameters show a higher value for granite samples than marble samples, primarily due to the presence of potassium feldspar minerals in these types of granites. marbles were observed to be radiologically safer than granite because they possess a neglected 40 K content and a trace quantity of uranium and thorium. Moreover, the minimum potassium content is enough to make a rock radiological unsafe due to 40 K only being determined to be about 13.2%. © 2024. The Author(s).
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10.1038/s41598-024-80298-1
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