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24211135 | SAHA enhances Proteostasis of epilepsy-associated α1(A322D)β2γ2 GABA(A) receptors. | GABA(A) receptors are the primary inhibitory ion channels in the mammalian central nervous system. The A322D mutation in the α1 subunit of GABA(A) receptors is known to result in its degradation and reduce its cell surface expression, leading to loss of GABAA receptor function in autosomal dominant juvenile myoclonic epilepsy. Here, we show that SAHA, a FDA-approved drug, increases the transcription of the α1(A322D) subunit, enhances its folding and trafficking posttranslationally, increases its cell surface level, and restores the GABA-induced maximal current in HEK293 cells expressing α1(A322D)β2γ2 receptors to 10% of that for wild-type receptors. To enhance the trafficking efficiency of the α1(A322D) subunit, SAHA increases the BiP protein level and the interaction between the α1(A322D) subunit and calnexin. SAHA is a drug that enhances epilepsy-associated GABAA receptor proteostasis. |
24211138 | Tracking brain palmitoylation change: predominance of glial change in a mouse model of Huntington's disease. | Protein palmitoylation, a reversible lipid modification of proteins, is widely used in the nervous system, with dysregulated palmitoylation being implicated in a variety of neurological disorders. Described below is ABE/SILAM, a proteomic strategy that couples acyl-biotinyl exchange (ABE) purification of palmitoyl-proteins to whole animal stable isotope labeling (SILAM) to provide an accurate tracking of palmitoylation change within rodent disease models. As a first application, we have used ABE/SILAM to look at Huntington's disease (HD), profiling palmitoylation change in two HD-relevant mouse mutants: the transgenic HD model mouse YAC128 and the hypomorphic Hip14-gt mouse, which has sharply reduced expression for HIP14 (Zdhhc17), a palmitoyl-transferase implicated in the HD disease process. Rather than mapping to the degenerating neurons themselves, the biggest disease changes instead map to astrocytes and oligodendrocytes (i.e., the supporting glial cells). |
24211140 | Pituitary macroadenoma causing symptomatic internal carotid artery compression: surgical treatment through transsphenoidal tumor resection. | Pituitary macroadenomas can invade the cavernous sinus and rarely cause occlusion of the internal carotid artery (ICA). Most patients with symptomatic obstruction of the ICA by a pituitary tumor have been reported as a result of apoplexy. The authors review the literature about this condition and report a 48-year-old man who presented with transient ischemic attacks leading to a stroke. Imaging studies plete occlusion of the left ICA and critical narrowing of the right ICA at the level of the clinoid processes, most likely due to macroadenoma mass effect. There was no radiologic evidence of apoplexy. Surgical resection of the tumor and ICA pression via the transsphenoidal route resulted in prevention of further symptoms. Histopathologic analysis confirmed a nonfunctioning pituitary adenoma without evidence of hemorrhage or intratumoral infarction. This patient, to the authors' knowledge, is the first documented patient with symptomatic pression by a pituitary adenoma without evidence of apoplexy. |
24211141 | Giant axonal neuropathy diagnosed on skin biopsy. | Evaluation of hereditary axonal neuropathy in childhood plex. Often, the child has to be subjected to general anaesthesia for a nerve biopsy to guide further genetic testing, which may or may not be readily available. We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding pound heterozygous mutations involving the GAN gene, including a novel interstitial microdeletion at 16q23.2 detected by microarray and a point mutation detected by direct sequencing. |
24211142 | Short-term outcome for saccular cerebral aneurysms treated with the Orbit Galaxy Detachable Coil System. | Technological advancement within the field of neuroendovascular therapy may lead to safer and more robust treatment options for patients with lesions traditionally not favorable to coil occlusion. We analyze and report our es with the Orbit Galaxy Detachable Coil System (DePuy Synthes, West Chester, PA, USA) for the treatment of anterior and posterior circulation saccular cerebral aneurysms. Patients treated with Orbit Galaxy coils for primary or recurrent saccular cerebral aneurysms from October 2010 to July 2012 were retrospectively reviewed using medical records, operative reports, and radiographs. Ninety-three patients, 69% unruptured and 31% ruptured, were treated with Orbit Galaxy coils for their anterior (80%) or posterior (20%) circulation saccular cerebral aneurysm. Primary treatment with Orbit Galaxy coils occurred in 84% of patients with an initial 100% occlusion rate of 65% while 16% had Galaxy coils placed into a "secondary" recurrent lesion. The overall incidence of recurrence was 26% with a mean interval of 7 months. Retreatment for recurrence was needed in 20 patients (22%). The mortality rate was 0%. A 2% incidence of rebleed was observed; each was after a secondary treatment. The morbidity of the treatment was low with 1% having a modified Rankin score greater than 3. Primary endovascular treatment of saccular cerebral aneurysms of the anterior and posterior circulation with the Orbit Galaxy Detachable Coil System is safe and effective in the short term. |
24211143 | Psychosis with obsessive-compulsive symptoms in tuberous sclerosis. | We present a case of tuberous plex (TSC) diagnosed in adulthood in a man initially referred for specialist neuropsychiatric assessment with psychosis and pulsive symptoms (OCS) on a background of epilepsy and intellectual disability. To our knowledge, this is the first reported patient with TSC featuring both psychosis and OCS. This patient highlights the importance prehensive re-evaluation of atypical presentations of intellectual disability, epilepsy and associated neuropsychiatric symptoms, even in adulthood. This is particularly relevant in the context of significant advances in genetics, neuroscience, imaging and treatments for heritable neurogenetic disorders. |
24211146 | A bioenergetic assessment of mitral regurgitation: a new tool to assess severity? | Mitral regurgitation is frequently classified as mild, moderate or severe based on echocardiography. Patients with mild mitral regurgitation are usually managed medically. We hypothesise that mild mitral regurgitation as assessed volumetrically can in fact be severe when analysed from a bioenergetics point of view. The conservation of energy predicts that any regurgitant volume will require the heart to provide more work energy to support the circulation. Mitral regurgitation involves the left ventricle imparting potential energy, via blood pressure, and kinetic energy, via regurgitant velocity, to the regurgitant blood volume. This implies that regurgitant volume, regurgitant velocity, systolic blood pressure, heart rate, regurgitant orifice area and cardiac output are all important factors. We present limited data to demonstrate our hypothesis. A bioenergetic analysis of mitral regurgitation, may identify patients whose mitral regurgitation, assessed via echocardiography as mild, is actually clinically significant. In addition we identify the importance of blood pressure and heart rate control in patients with mitral regurgitation. The concept that a bit of mitral regurgitation in patients with poor left ventricles is a good thing, as it helps offload the left ventricle is from an engineering point fundamentally flawed. |
24211145 | Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: a conceptual framework. | Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to itantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the ponents in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection. |
24211144 | C-reactive protein and long-term ischemic stroke prognosis. | C-reactive protein (CRP) is an inflammatory biomarker of inflammation and may reflect progression of vascular disease. Conflicting evidence suggests CRP may be a prognostic biomarker of ischemic stroke e. Most studies that have examined the relationship between CRP and ischemic stroke e have used mortality or subsequent vascular event as the primary e measure. Given that nearly half of stroke patients experience moderate to severe functional impairments, using a biomarker like CRP to predict functional recovery rather than mortality may have clinical utility for guiding acute stroke treatments. The primary aim of this study was to systematically and critically review the relationship between CRP and long-term functional e in ischemic stroke patients to evaluate the current state of the literature. PubMed and MEDLINE databases were searched for original studies which assessed the relationship between acute CRP levels measured within 24 hours of symptom onset and long-term functional e. The search yielded articles published between 1989 and 2012. Included studies used neuroimaging to confirm ischemic stroke diagnosis, high-sensitivity CRP assay, and a functional e scale to assess prognosis beyond 30 days after stroke. Study quality was assessed using the REMARK mendations. Five studies met all inclusion criteria. Results indicate a significant association between elevated baseline high sensitivity CRP and unfavorable long-term functional e. Our results emphasize the need for additional research to characterize the relationship between acute inflammatory markers and long-term functional e using well-defined diagnostic criteria. Additional studies are warranted to prospectively examine the relationship between high sensitivity CRP measures and long-term e. |
24211147 | Attention Bias Modification Treatment for children with anxiety disorders who do not respond to cognitive behavioral therapy: a case series. | Evidence is emerging to support the promise of Attention Bias Modification Treatment (ABMT), puter-based attention training program, in reducing anxiety in children. ABMT has not been tested as an adjuvant for children with anxiety disorders who do not respond to Cognitive-Behavioral Therapy (CBT). This case series presents findings from an open trial of ABMT among six children (four girls; M age = 11.2 years) pleted a CBT protocol and continued to meet diagnostic criteria for an anxiety disorder. All pleted the ABMT protocol with no canceled or missed sessions. Child self-ratings on anxiety symptoms and depressive symptoms significantly decreased from pretreatment to posttreatment, as did parent ratings on child anxiety-related impairment. Parent ratings on child anxiety and internalizing symptoms displayed non-significant decreases from pretreatment to posttreatment. These findings support the potential promise of ABMT as a feasible adjuvant treatment that reduces anxiety and impairment among child anxiety CBT nonresponders. |
24211148 | Personality disorders and the persistence of anxiety disorders: evidence of a time-of-measurement effect in NESARC. | Recent studies using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) have found that some personality disorders (PDs) increase the persistence of several Axis I disorders. However, these effects are potentially confounded with the data collection wave in which PDs were assessed. Our aim was to extend published analyses to the case of anxiety disorders and to determine the robustness of the associations to analyses examining time-of-measurement effects. Persistence of anxiety disorders was defined either as follow-up diagnosis among participants diagnosed at baseline ("prediction") or baseline diagnosis among participants diagnosed at follow-up ("post-diction"). Results revealed a robust pattern of higher odds ratios for post-diction among PDs assessed at baseline, and lower odds ratios for post-diction among PDs assessed at follow-up, suggesting a time of measurement artifact. Although only 4% of associations were robust to both predictive and post-dictive analyses, these were consistent with previous research. |
24211149 | [Generic substitution in primary care in 2011: differences according to pharmacological classes?]. | Generic substitution has been permitted for several years in France and is promoted in order to reduce health expenditures. However, reluctance concerning use of generic drugs exists for different reasons: suspicions about their efficacy and/or safety, differences in content (excipients) and discussions about bioequivalency. The aim of our study was to determine whether or not the substitution ratio differs according to pharmacological classes used in primary care. |
24211150 | Screen time, cardiorespiratory fitness and adiposity among school-age children from Monteria, Colombia. | To explore the association between electronic media exposure (television viewing time, puter/video game use, total screen time), and waist circumference and body mass index, and study whether this association is independent of cardiorespiratory fitness, in a representative sample of adolescents from Montería, Colombia. |
24211151 | Socioeconomic deprivation independently predicts symptomatic painful diabetic neuropathy in type 1 diabetes. | Painful peripheral neuropathy in people with type 1 diabetes is a disabling and plication. A greater understanding of predisposing factors and prescribing may facilitate more effective resource allocation. |
24211152 | Childhood cancer in Aden, Yemen. | Cancer in children is increasingly recognized as a major and growing health problem in different developed and developing countries. In Yemen, it is still difficult to know the extent of cancer and its determinants among children. This study was conducted to determine the magnitude of childhood cancer in Aden and provide the preliminary baseline data by age and sex. |
24211154 | Efficacy of a static progressive stretch device as an adjunct to physical therapy in treating adhesive capsulitis of the shoulder: a prospective, randomised study. | Stress relaxation and static progressive stretch are techniques used for non-surgical restoration of shoulder range of motion for patients with adhesive capsulitis. |
24211153 | Patient navigation pathway and barriers to treatment seeking in cancer in India: a qualitative inquiry. | Cancer is a leading cause of mortality worldwide. Early diagnosis and treatment of cancer may curb the growing burden of the disease. Understanding cancer patients' navigation pathways for seeking treatment is important in order to facilitate early diagnosis and treatment. With this background we conducted a hospital-based cross-sectional prising 68 randomly selected cancer inpatients in a tertiary cancer specialty hospital in Odisha, India, to explore the treatment-seeking pathways of the cancer patients and the barriers and enablers in seeking treatment. Financial constraint is one of the major reasons for the delay in accessing treatment, even when patients are suspected of or diagnosed with cancer. Low awareness of the presenting signs and symptoms of cancer and limited knowledge of the availability of cancer diagnosis and treatment facilities are major factors contributing to delay. Family and friends' support is found to be the major enabling factor toward seeking treatment. Generation of awareness of cancer among the general population and primary-care practitioners - including those in alternative systems of medicine - is important. Information on diagnostic and treatment services appears to be a felt need. |
24211155 | The entry of Colombian-sourced heroin into the US market: the relationship between competition, price, and purity. | There have been large structural changes in the US heroin market over the past 20 years. Colombian-sourced heroin entered the market in the mid-1990s, followed by a large fall in the price per pure gram and the exit of Asian heroin. By the 2000s, Colombian-sourced heroin had e a monopoly on the east coast and Mexican-sourced heroin a monopoly on the west coast petition between the two in the middle. We estimate the relationship between these changes petitive market structure on retail-level heroin price and purity. We find that the entry of Colombian-sourced heroin is associated with petition and a lower price per pure gram of heroin at the national level. However, there is wide variation in changes in market concentration across the US. Controlling for the national fall in the heroin price, petition in a region or city is associated with a lower price per pure gram. |
24211159 | Inhalation and dietary exposure to Dechlorane Plus and polybrominated diphenyl ethers in Osaka, Japan. | This study estimated daily exposure to Dechlorane Plus (DP) and polybrominated diphenyl ethers (PBDE) via inhalation and diet. Samples of atmospheric particles and food (obtained by market basket method) from Osaka, Japan were analyzed for DP (syn-, anti-) and PBDE using gas chromatography-mass spectrometry. DP was detected in both atmospheric particles and food samples. Among the atmospheric particles, DP was detected in all samples. ΣDP concentration was 7.1-15.4 pg m(-3) and anti-DP was the dominant residue among DP isomers. PBDE was also detected in all the atmospheric particles. ΣPBDE concentration was 9.9-23.3 pg m(-3). In the market basket study, DP was detected in Groups Ш (sugar and confectionary), V (legumes and their products), X (fish, shellfish, and their products), and XI (meat and eggs) at concentrations of 3.3, 2.8, 1.9, and 1.5 pg g(-1) wet wt, respectively. PBDE was detected in Groups Ш, IV (oils and fats), V, X, XI, and XШ (seasonings and other processed foods) at concentrations of 153, 79.1, 74.6, 308, 94.8, and 186 pg g(-1) wet wt, respectively. The daily intake of ΣDP (750 pg day(-1)) via inhalation and diet was approximately one percent of that for ΣPBDE (62 ng day(-1)). |
24211157 | The missing 'P' in pain management: how the current opioid epidemic highlights the need for psychiatric services in chronic pain care. | The prevalence of opioid therapy for chronic noncancer pain has increased dramatically in recent years, with a parallel increase in opioid abuse, misuse and deaths from accidental overdose. We review epidemiological and clinical data that point to the important roles psychiatric disorders have in the use and abuse of opioids in patients with chronic pain. |
24211160 | Polycyclic aromatic hydrocarbons in oysters and sediments from the Yatsushiro Sea, Japan: comparison of potential risks among PAHs, dioxins and dioxin-like compounds in benthic organisms. | Polycyclic aromatic hydrocarbons (PAHs) were analyzed in oysters collected from 18 stations in the Yatsushiro Sea, western Japan. PAHs were detected in all samples analyzed, and the highest concentration (mean 230 ng/g wet weight) was found in oysters from Tanoura Bay. The high molecular weight PAHs to low molecular weight PAHs ratios in oysters from Tanoura Bay were higher than at other stations. Sediment samples collected from 42 stations in Tanoura Bay were analyzed for PAHs to understand their concentrations and distribution. Higher concentrations were found in sediment samples at two stations in the southern inner bay (mean 30,200 ng/g dry weight), which were approximately two orders of magnitude higher than at a reference site. These observations strongly suggest severe contamination and significant sources of PAHs in Tanoura Bay. Dioxins and pounds (PCDFs, and non- and mono-ortho coplanar PCBs) were analyzed in sediments from eight stations in Tanoura Bay. The concentrations parable to, or lower than, at the reference sites, suggesting that there are no specific sources of pounds in this bay. PAH, dioxins and pounds DR-CALUX relative potencies (REP) were applied to the sediment concentrations to evaluate the potential for toxicological effects on benthic organisms. PAHs made the highest contribution to the total REP concentration, supplying 99% of the total REP, followed by PCDDs (0.18%), PCDFs (0.04%), and PCBs (<0.001%). In this area, PAHs appear to be the most important Ah receptor binding chemicals for potential toxicity to benthic species. |
24211161 | Impact of the IASLC/ATS/ERS classification in pN0 pulmonary adenocarcinomas: a study with radiological-pathological comparisons and survival analyses. | The aim of this study was: (1) pare the new pathological findings as detected by the IASLC/ATS/ERS classification with the traditional radiological features in pulmonary pN0 adenocarcinomas, (2) to evaluate their prognostic significance on overall survival (OS). A total of 42 surgically resected pN0 pulmonary adenocarcinomas were analyzed. On CT scans, the following radiological data were recorded: sphericity, predominant margins, cavitation and bronchogram, attenuation and percentage of ground glass opacity (GGO). On pathological examination, tumors were categorized according to the IASLC/ATS/ERS classification; Sica score and grade, pathological stage, tumor major axis, pleural invasion, vascular and lymphatic invasion, peritumoral lymphoid infiltration, and cytological features were also determined. Clinical follow up was available in 37 cases (range 1-117 months). Radiologically, 31 solid and 11 semisolid tumors were found. Morphologically, 2 minimally invasive and 40 invasive adenocarcinomas were diagnosed. In parisons, (1) the acinar pattern was higher in tumors with solid attenuation and low GGO (p=0.018); (2) the lepidic pattern was more elevated in tumors with high GGO (p=0.012). In multivariate survival analyses with stage, predominant margins on CT scans (p=0.036) and Sica score (p=0.028) significantly affected OS. This study confirms the validity of the new classification of pulmonary adenocarcinomas in parisons and underlines the importance of both radiological and pathological findings in correctly identifying their prognostic features. |
24211156 | Holding back sharing concerns, dispositional emotional expressivity, perceived unsupportive responses and distress among women newly diagnosed with gynecological cancers. | Little attention has been paid to the role of holding back sharing concerns in the psychological adaptation of women newly diagnosed with gynecological cancers. The goal of the present study was to evaluate the role of holding back concerns in psychosocial adjustment and quality of life, as well as a possible moderating role for emotional expressivity and perceived unsupportive responses from family and friends. |
24211162 | Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice. | Endothelial lipase (EL) activity has been implicated in HDL metabolism and in atherosclerotic plaque development; inhibitors are proposed to be efficacious in the treatment of dyslipidemia related cardiovascular disease. We describe here the discovery of a novel class of anthranilic acids EL inhibitors. XEN445 (compound 13) was identified as a potent and selective EL inhibitor, that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice. |
24211158 | The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis: a comparative study. | The aim of this study was to examine the current prevalence of major depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis (HT) and euthyroid goiter. |
24211163 | Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. | Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. |
24211166 | Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England. | Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary e if the subsequent impact on cervical cancer is to be realised. |
24211167 | Evaluating the efficacy of rBmHATαc as a multivalent vaccine against lymphatic filariasis in experimental animals and optimizing the adjuvant formulation. | Developing an effective vaccine against lymphatic filariasis plement the WHO's effort to eradicate the infection from endemic areas. Currently 83 different countries are endemic for this infection and over 1 billion people are at risk. An effective vaccine coupled with mass drug administration will reduce the morbidity and social stigma associated with this gruesome disease. Several potential vaccine candidates that can confer partial protection in experimental animals have been reported from different laboratories. However, no licensed vaccines are currently available for this disease. Among the several vaccine antigens identified from our laboratory, three most promising antigens; rBmHSPαc (α crystalline domain and c-terminal extension of Heat Shock Protein 12.6), rBmALT-2 (Abundant larval transcript) and rBmTSP LEL (Tetraspanin large extracellular loop) was further developed as a binant fusion protein vaccine (rBmHATαc). In a mouse model this fusion protein vaccine gave close to 68% protection following a challenge infection. To improve the vaccine efficiency of rBmHATαc, in this study we evaluated various preparations of alum (AL007, AL019, Alhydrogel and Imject® Alum) as adjuvants. Our results show that mice immunized with rBmHATαc formulated in AL007 (alum from IDRI) and/or AL019 (alum plus TLR-4 agonist from IDRI) gave the highest IgG antibody pared to other groups. Subsequent in vivo challenge experiments confirmed that >95% protection can be achieved when AL007 or AL019 was used as the adjuvant. However, when Imject® Alum or alhydrogel was used as the adjuvant only 76% and 72% protection respectively could be achieved. These results show that AL007 or AL019 (IDRI) is an excellent choice of adjuvant for the rBmHATαc vaccine against B. malayi L3 in mice. |
24211168 | Computational designing of a poly-epitope fecundity vaccine for multiple species of livestock. | Inhibin and follistatin are known to reduce fecundity by inhibiting the actions of activin and FSH. Thus, the immunoneutralization of these hormones is a rational proposal for augmenting reproductive performance. The present study describes putational prising of a consensus approach of several B- and Th-cell epitope prediction tools for the identification of epitopic regions within the structure of these hormones that can be incorporated into a poly-epitope fecundity vaccine. The proposed peptide (RGD-WSPAALRLLQRPPEEPA-KK-YSFPISSILE) should be effective in multiple animal species, generating good immunological memory. |
24211169 | A modified surface killing assay (MSKA) as a functional in vitro assay for identifying protective antibodies against pneumococcal surface protein A (PspA). | Streptococcus pneumoniae causes otitis media, meningitis and pneumonia in patients worldwide; predominantly affecting young children, the elderly, and the promised. Current vaccines against invasive pneumococcal disease are based on the polysaccharide capsules of the most clinically relevant serotypes. Due to serotype replacement, non-vaccine serotypes of S. pneumoniae have e more clinically relevant and as a result pneumococcal vaccines are ing plex. These events emphasize the need to evaluate the potential for pneumococcal cross-reactive proteins to contribute to future vaccines. Antibody elicited by the immunization of humans with pneumococcal surface protein A (PspA) can passively protect mice from infection. However, robust in vitro functional assays for antibody to PspA are not available to predict the protective capacity of immune serum. For polysaccharide based vaccines, a standardized opsonophagocytosis killing assay (OPKA) is used. Antibody to PspA, however, does not work well in the standard OPKA. The present studies take advantage of past observations that phagocytosis is more efficient on tissue surfaces than in solution. In a modified surface killing assay (MSKA), monoclonal antibody to PspA, in the presence plement, opsonized pneumococci for killing by phagocytes on an agar surface. Five monoclonal antibodies to PspA were tested; three demonstrated increased amounts of pared to the diluent control and protected mice by passive protection against type 3 pneumococci. The two antibodies that were not functional in the MSKA also failed to protect mice. Thus, an MSKA might be useful as a functional assay for immunity to PspA. |
24211170 | Human papillomavirus vaccination and Pap testing profile in Manitoba, Canada. | Females who receive the human papillomavirus (HPV) vaccine may believe they are protected from developing cervical cancer and no longer require screening. Concern has also been expressed that vaccinated females are those that would be screened regularly. This study assesses the Pap testing behavior of vaccinated and non-vaccinated females. |
24211173 | Trans- and cis-stilbene isolated in cryogenic argon and xenon matrices. | Monomers of trans- (TS) and cis-stilbene (CS) were isolated in cryogenic argon and xenon matrices, and their infrared (IR) spectra were fully assigned and interpreted. The interpretation of the vibrational spectra received support from theoretical calculations undertaken at the DFT(B3LYP)/6-311++G(d,p) level of theory. In situ broadband UV irradiation of the matrix-isolated CS led to its isomerization to TS, which appeared in the photolysed matrices in both non-planar and planar configurations. The non-planar species was found to convert into the more stable planar form upon subsequent annealing of the matrices at higher temperature. TS was found to be photostable under the used experimental conditions. The structure of the non-planar TS form was assigned based on parison of its observed IR spectrum with those theoretically predicted for different conformations of TS. Chemometrics was used to make this assignment. Additional reasoning on the structure of the studied stilbenes is presented taking as basis results of the Natural Bond Orbital analysis. |
24211172 | Randomized trial of a home monitoring system for early detection of choroidal neovascularization home monitoring of the Eye (HOME) study. | To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in earlier detection of age-related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, pared with standard care. The main predictor of treatment e from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment. |
24211171 | [Prevalence and functions of self-injurious thoughts and behaviors in a sample of Spanish adolescents assessed in mental health outpatient departments]. | Suicidal and self-injurious behaviors in adolescents are a major public health concern. However, the prevalence of self-injurious thoughts and behaviors in Spanish outpatient adolescents is unknown. |
24211175 | Stability of acute dorsal fracture dislocations of the proximal interphalangeal joint: a biomechanical study. | We performed a cadaveric biomechanical study to characterize proximal interphalangeal joint stability after an injury to different amounts of the volar articular base of the middle phalanx (intact, 20%, 40%, 60%, and 80% volar defects). |
24211178 | Facial emotion recognition and its correlation with executive functions in bipolar I patients and healthy controls. | The ability to recognize facial emotions is altered in patients with Bipolar Disorder (BD) during mood episodes and even in euthymia, while cognitive functioning is similarly impaired. This recognition is considered a fundamental skill for successful social interaction. However, it is unclear whether the ability to recognize facial emotions is correlated with the cognitive deficits observed in BD. |
24211179 | Biological sulfate removal from construction and demolition debris leachate: effect of bioreactor configuration. | Due to the contamination of construction and demolition debris (CDD) by gypsum drywall, especially, its sand fraction (CDD sand, CDDS), the sulfate content in CDDS exceeds the posed limit of the maximum amount of sulfate present in building sand (1.73 g sulfate per kg of sand for the Netherlands). Therefore, the CDDS cannot be reused for construction. The CDDS has to be washed in order to remove most of the impurities and to obtain the right sulfate content, thus generating a leachate, containing high sulfate and calcium concentrations. This study aimed at developing a biological sulfate reduction system for CDDS leachate treatment pared three different reactor configurations for the sulfate reduction step: the upflow anaerobic sludge blanket (UASB) reactor, inverse fluidized bed (IFB) reactor and gas lift anaerobic membrane bioreactor (GL-AnMBR). This investigation demonstrated that all three systems can be applied for the treatment of CDDS leachate. The highest sulfate removal efficiency of 75-85% was achieved at a hydraulic retention time (HRT) of 15.5h. A high calcium concentration up to 1,000 mg L(-1) did not give any adverse effect on the sulfate removal efficiency of the IFB and GL-AnMBR systems. |
24211180 | Evaluation of the phototransformation of the antiviral zanamivir in surface waters through identification of transformation products. | The antiviral zanamivir has been recently reported to occur in surface waters where its presence may lead to the selection of resistant strains of virus in aquatic fauna. In order to evaluate the fate of zanamivir in surface waters, its susceptibility to phototransformation was evaluated using simulated and natural sunlight. Upon exposure of aqueous solutions (20μgL(-1)) to simulated sunlight, zanamivir in surface water degraded at t1/23.6h. Under natural sunlight in surface water about 30% of the initial concentration of the antiviral disappeared within 18 days. The experiments with surface water showed similar effect as humic acid addition with expected decreasing effect on degradation while nitrate addition showed increasing effect. In the experiments with artificial sunlight at high concentrations of zanamivir, four photoproducts were tentatively identified by hydrophilic interaction chromatography-LTQ-Orbitrap-MS, showing [M+H](+) ions at m/z 112 (TP111), m/z 275 (TP274), m/z 323 (TP322), and m/z 333 (TP332). However at 20μgL(-1) only the formation of the recalcitrant TP111 was observed. The proposed structures were rationalized by photolysis mechanisms. Photoproduct TP111 was confirmed with mercially available standard (isocytosine). In summary, the findings suggest that the photodegradation of zanamivir in surface waters proceeds with slow kinetics. |
24211181 | Blood disorders after kidney transplantation. | Post transplant anemia (PTA) is mon issue in kidney transplant recipients. Most importantly it is associated with an impaired allograft function. Other important factors associated with PTA are immunosuppressive drugs (MPA, AZA and SRL), iron deficiency, infections (Parvo B19), older donor age, rejection episodes, an increased inflammatory state, and erythropoietin hyporesponsiveness. As there are no adequately powered RCTs in the kidney transplant population on anemia treatment with ESA, we have to rely on what we know from the large RCTs in the CKD population. The recently published KDIGO guidelines do not mend treatment with ESA if Hb is >10 g/dl. Repletion of iron stores is emphasized. Post transplant leukopenia (PTL) and thrombocytopenia (PTT) are plications especially in the first six months after kidney transplantation. Myelosuppression caused by immunosuppressive agents (MPA, AZA, SRL, rATG), antimicrobial drugs (VGCV), and CMV infection is the predominant cause. There are no widely accepted guidelines on treatment strategies, but most often dose reduction or discontinuation of causative medication is done. Most clinicians tend to decrease MPA dose, but this is eventually associated with an increase in acute rejection episodes. VGCV dose reduction (preemptive treatment instead of CMV prophylaxis) may be a successful strategy. In severe cases G-CSF treatment is an important management option and seems to be safe. |
24211182 | Gating pluripotency via nuclear pores. | In recent years, growing evidence has pointed to the interesting idea that pluripotency might be regulated by a nuclear-pore-coordinated network that controls the level of pluripotency factors in the nucleus. A thorough understanding of this process might improve prehension of cell pluripotency and differentiation during embryogenesis, as well as aiding the development of novel models for studying human diseases. |
24211183 | Tumor necrosis factor receptor signaling in keratinocytes triggers interleukin-24-dependent psoriasis-like skin inflammation in mice. | Psoriasis is mon chronic inflammatory skin disease with a prevalence of about 2% in the Caucasian population. Tumor necrosis factor (TNF) plays an essential role in the pathogenesis of psoriasis, but its mechanism of action remains poorly understood. Here we report that the development of psoriasis-like skin inflammation in mice with epidermis-specific inhibition of the transcription factor NF-κB was triggered by TNF receptor 1 (TNFR1)-dependent upregulation of interleukin-24 (IL-24) and activation of signal transducer and activator of transcription 3 (STAT3) signaling in keratinocytes. IL-24 was strongly expressed in human psoriatic epidermis, and pharmacological inhibition of NF-κB increased IL-24 expression in TNF-stimulated human primary keratinocytes, suggesting that this mechanism is relevant for human psoriasis. Therefore, our results expand current views on psoriasis pathogenesis by revealing a new keratinocyte-intrinsic mechanism that links TNFR1, NF-κB, ERK, IL-24, IL-22R1, and STAT3 signaling to disease initiation. |
24211184 | Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. | Upon infection, CD8(+) T cells undergo a stepwise process of early activation, expansion, and differentiation into effector cells. How these phases are transcriptionally regulated is pletely defined. Here, we report that interferon regulatory factor 4 (IRF4), dispensable for early CD8(+) T cell activation, was vital for sustaining the expansion and effector differentiation of CD8(+) T cells. Mechanistically, IRF4 promoted the expression and function of Blimp1 and T-bet, two transcription factors required for CD8(+) T cell effector differentiation, and simultaneously repressed genes that mediate cell cycle arrest and apoptosis. Selective ablation of Irf4 in peripheral CD8(+) T cells impaired antiviral CD8(+) T cell responses, viral clearance, and CD8(+) T cell-mediated host recovery from influenza infection. IRF4 expression was regulated by T cell receptor (TCR) signaling strength via mammalian target of rapamycin (mTOR). Our data reveal that IRF4 translates differential strength of TCR signaling into different quantitative and qualitative CD8(+) T cell responses. |
24211185 | The haplosporidian Bonamia exitiosa is present in Australia, but the identity of the parasite described as Bonamia (formerly Mikrocytos) roughleyi is uncertain. | Protistan oyster parasites in the genus Bonamia have been observed in recent years infecting new hosts on five continents, with most of these parasites genetically similar to austral species Bonamia exitiosa and Bonamia roughleyi. Identification of the newly observed parasites as one or another of these described species has plicated by the fact that B. exitiosa and B. roughleyi are phylogenetically indistinguishable at the small-subunit ribosomal DNA (SSU rDNA) level, with samples of B. roughleyi type material no longer available for genetic re-analyses using more informative internal transcribed spacer (ITS) region DNA sequences. To resolve this issue, we evaluated B. roughleyi in field collections of hosts Saccostrea glomerata and Ostrea angasi (as well as Crassostrea gigas) in New South Wales, Australia in 2006 and 2007, and re-analyzed histological samples from the original description of this parasite species using in situ hybridization. Despite (1) reports of the oyster disease putatively caused by B. roughleyi during the time of collections, (2) the observation of gross lesions characteristic of the disease, and (3) the observation of B. roughleyi cells in association with the lesions, we detected a Bonamia sp. by PCR in just 1/42 O. angasi (2.4%), and 1/608 S. glomerata (0.2%), the latter oyster of which is the type host. SSU rDNA sequences of the amplicons were nearly identical to those of B. exitiosa and B. roughleyi, and phylogenetic analysis of ITS region sequences placed them on a B. exitiosa clade. A Haplosporidium sp. sequence similar to that of H. costale was PCR-amplified from nearly half the S. glomerata and O. angasi, but no Haplosporidium sp. was observed histologically. Our inability to identify a Bonamia sp. sequence in association with the B. roughleyi observed histologically suggests that this parasite is not a Bonamia sp. at all, and should be regarded as B. roughleyi nomen dubium. We conclude that the Bonamia sp. that we and other investigators detected in southeastern Australian S. glomerata and O. angasi was B. exitiosa. |
24211186 | Advantages of QBI in TBSS analyses. | Diffusion-weighted magnetic resonance imaging (DWMRI) is used to study white matter (WM) in normal and clinical populations. In DWMRI studies, diffusion tensor imaging (DTI) models the WM anisotropy with one dominant direction, detecting possible pathway abnormalities only in large and highly coherent fiber tracts. However, more general anisotropy models like Q-ball imaging (QBI) may provide more sensitive WM descriptors in single patients. The present study aimed pare DTI and QBI models in a group-level population analysis, using Amyotrophic Lateral Sclerosis (ALS) as a pathological case model of WM tract degeneration. DWMRI was performed in 19 ALS patients and 19 age and sex-matched healthy controls. DTI and QBI estimates pared in whole-brain tract-based spatial statistics (TBSS) and volume of interest (VOI) analyses, and correlated with ALS clinical scores of disability. A significant decrease of the QBI-derived generalized fractional anisotropy (GFA) was observed in both motor and extramotor fibers of ALS pared to controls. Homologue DTI-derived FA maps were only partially overlapping with GFA maps. Particularly, the left corticospinal tracts resulted more markedly depicted by the QBI than by the DTI model, with GFA predicting ALS disability better than FA. The present findings demonstrate that QBI model is suitable for studying WM tract degeneration in population-level clinical studies. Particularly, group-level studies of fiber integrity may benefit from QBI when DTI is biased towards low values, such as in cases of fiber degeneration, and in regions with more than one dominant fiber direction. |
24211187 | Effects of RF profile on precision of quantitative T2 mapping using dual-echo steady-state acquisition. | The dual echo steady-state (DESS) sequence has been shown successful in achieving fast T2 mapping with good precision. Under-estimation of T2, however, es increasingly prominent as the flip angle decreases. In 3D DESS imaging, therefore, the derived T2 values would e a function of the slice location in the presence of non-ideal slice profile of the excitation RF pulse. Furthermore, the pattern of slice-dependent variation in T2 estimates is dependent on the RF pulse waveform. Multi-slice 2D DESS imaging provides better inter-slice consistency, but the signal intensity is subject to integrated effects of within-slice distribution of the actual flip angle. Consequently, T2 measured using 2D DESS is prone to inaccuracy even at the designated flip angle of 90°. In this study, both phantom and human experiments demonstrate the above phenomena in good agreement with model prediction. |
24211188 | Robust GRAPPA reconstruction using sparse multi-kernel learning with least squares support vector regression. | Accuracy of interpolation coefficients fitting to the auto-calibrating signal data is crucial for k-space-based parallel reconstruction. Both conventional generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstruction that utilizes linear interpolation function and nonlinear GRAPPA (NLGRAPPA) reconstruction with polynomial kernel function are sensitive to interpolation window and often cannot consistently produce good results for overall acceleration factors. In this study, sparse multi-kernel learning is conducted within the framework of least squares support vector regression to fit interpolation coefficients as well as to reconstruct images robustly under different subsampling patterns and coil datasets. The bination weights and interpolation coefficients are adaptively determined by efficient semi-infinite linear programming techniques. Experimental results on phantom and in vivo data indicate that the proposed method can automatically achieve an promise between noise suppression and residual artifacts for various sampling schemes. Compared with NLGRAPPA, our method is significantly less sensitive to the interpolation window and kernel parameters. |
24211190 | Family-wide expression characterization of Arabidopsis beta-carbonic anhydrase genes using qRT-PCR and Promoter::GUS fusions. | Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes found throughout the phylogenetic tree. The β-class carbonic anhydrases (β-CAs) are the predominating class of CAs in plants. Growing evidence underscores the importance of β-CAs in plant immunity and environmental adaptation in addition to their roles in photosynthesis. However, many fundamental problems in Arabidopsis βCAs expression remain unsolved. Here we examined the transcript abundance of AtβCAs in different tissues of Arabidopsis thaliana, and the accumulation of mRNA in response to CO2 and darkness. Histochemical analysis was performed to study the promoter activity of AtβCAs during post-germination seedling growth and in mature plants. All six members of the AtβCA subfamily showed a response to changed CO2 level and darkness, but each member showed a specific dynamic pattern. Although expression of each AtβCA was unique, in general most AtβCAs were synchronously expressed in green leaves since 5 days after germination until flowering. AtβCA1 and AtβCA2 were most highly expressed in leaves but AtβCA2 displayed weaker expression in roots. The level of AtβCA3 transcripts was highest in flowers, while AtβCA5 was most widely expressed and might be involved in more processes than other members. AtβCA6 was unique for increased expression in darkness and no expression in either the anther or pistil. The present study provides useful information for further functional investigation. |
24211189 | CP12-mediated protection of Calvin-Benson cycle enzymes from oxidative stress. | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) are two energy-consuming enzymes of the Calvin-Benson cycle, whose regulation is crucial for the global balance of the photosynthetic process under different environmental conditions. In oxygen phototrophs, GAPDH and PRK regulation involves the redox-sensitive protein CP12. In the dark, oxidized chloroplast thioredoxins trigger the formation of a plex in which both enzyme activities are down-regulated. In this report, we show that free GAPDH (A4-isoform) and PRK are also inhibited by oxidants like H2O2, GSSG and GSNO. Both in the land plant Arabidopsis thaliana and in the green microalga Chlamydomonas reinhardtii, both enzymes can be glutathionylated as shown by biotinylated-GSSG assay and MALDI-ToF mass spectrometry. CP12 is not glutathionylated but homodisulfides are formed upon oxidant treatments. In Arabidopsis but not in Chlamydomonas, the interaction between oxidized CP12 and GAPDH provides full protection from oxidative damage. In both organisms, preformed plexes are protected from GSSG or GSNO oxidation, and in Arabidopsis also from H2O2 treatment. Overall, the results suggest that the role of CP12 in oxygen phototrophs needs to be extended beyond light/dark regulation, and include protection of enzymes belonging to Calvin-Benson cycle from oxidative stress. |
24211191 | CARM1 and PRMT1 are dysregulated in lung cancer without hierarchical features. | CARM1 and PRMT1 are 2 Protein Arginine Methyl Transferases (PRMT) dysregulated in cancer. CARM1 function is contradictory and depicted as facilitating proliferation or differentiation. PRMT1 is required for cell proliferation. CARM1 and PRMT1 cooperate for gene regulation. We report that CARM1 and PRMT1 are significantly overexpressed in 60 patients with Non-Small Cell Lung Carcinomas (NSCLC). CARM1 and PRMT1 correlated in healthy but not tumor tissue. Their levels of expression in tumor tissue were proportional to their levels of expression in the counterpart healthy tissue. Only CARM1 expression was found to be correlated with tumor differentiation and neither CARM1 nor PRMT1 expression was correlated with survival. Accordingly, CARM1 and PRMT1 are overexpressed in 2 NSCLC cell lines, A549 and H1299. Targeting PRMT1 with siRNA reduced proliferation, by decreasing cell growth and inhibiting soft agar colony formation, and promoted differentiation, by increasing the epithelial markers cytokeratin 7 and 8 and decreasing Neuromedin B receptor, which binds a mitogenic factor. siCARM1 yielded similar consequences but the conditions with siCARM1 reflected inhibition of both CARM1 and PRMT1. Together these results suggest that CARM1 and PRMT1 are involved in proliferation in lung cancer with no hierarchy of one protein over the other. The fact that CARM1 targeting suppresses PRMT1 in addition to CARM1 reinforces the functional importance of CARM1/PRMT1 interaction. |
24211192 | The effect of a telephone follow-up intervention on illness perception and lifestyle after myocardial infarction in China: a randomized controlled trial. | Lifestyle modification is an ponent of cardiac secondary prevention, while it has been confirmed that myocardial infarction (MI) patients' health-related behaviors are heavily influenced by their illness perception. |
24211193 | New Caledonian lineages of Psychotria (Rubiaceae) reveal different evolutionary histories and the largest documented plant radiation for the archipelago. | New Caledonia is a remote archipelago of the South-West Pacific, whose flora is rich, distinctive, and disharmonic. The interest of botanists has long been attracted by the spatio-temporal origin of this flora, but little attention has been paid to the modes of colonization and the diversification processes that have led to the archipelago's modern flora. To date, no explosive plant radiation has yet been highlighted for New Caledonia. A dated phylogenetic framework on the second richest New Caledonian genus--Psychotria s.l. and its allied genera (tribes Psychotrieae and Palicoureeae, Rubiaceae; ca. 85 species)--is provided in this study to explore its patterns of colonization and diversification in the archipelago. This study is based on prehensive species sampling, two nuclear and four plastid loci. Results show that New Caledonia was colonized four times by Psychotria and its allied genera during the Neogene long after its mid-Eocene re-emergence from the sea. The Pacific clade of Psychotrieae, one of the largest plant diversifications in the Pacific islands and the Indo-Pacific region, is absent from New Caledonia, possibly due to petition. Although the four lineages colonized New Caledonia relatively simultaneously during the Neogene, they express different evolutionary histories, as revealed by unevenness in species richness and net diversification rates. The genus Geophila has not diversified on New Caledonia, as a non-endemic single species has been documented in the archipelago. The genus Margaritopsis had a moderate level of diversification (four species) similar to that on other Pacific islands. The Psychotria clade NC1 appears to be a relictual lineage, which probably underwent a drastic extinction, with a narrow ecological habitat and dispersal limitations. The Psychotria clade NC2 is the largest and youngest New Caledonian plant radiation, and has undergone the fastest recorded diversification of any endemic lineage in the archipelago, and could be the result of a 'non-adaptive radiation', originating from Australian rainforests. |
24211195 | [Diagnostic reference levels in interventional radiology]. | This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP mends that plexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. |
24211196 | [State of the art and future trends in technology for computed tomography dose reduction]. | The introduction of helical and multislice acquisitions in CT scanners together with decreased image reconstruction times has had a tremendous impact on radiological practice. Technological developments in the last 10 to 12 years have enabled very high quality images to be obtained in a very short time. Improved image quality has led to an increase in the number of indications for CT. In parallel to this development, radiation exposure in patients has increased considerably. Concern about the potential health risks posed by CT imaging, reflected in diverse initiatives and actions by official organs and scientific societies, has prompted the search for ways to reduce radiation exposure in patients promising diagnostic efficacy. To this end, good practice guidelines have been established, special applications have been developed for scanners, and research has been undertaken to optimize the clinical use of CT. Noteworthy technical developments incorporated in scanners include the different modes of X-ray tube current modulation, automatic selection of voltage settings, selective organ protection, adaptive collimation, and iterative reconstruction. The appropriate use of these tools to reduce radiation doses requires thorough knowledge of how they work. |
24211197 | Detecting ligand interactions with G protein-coupled receptors in real-time on living cells. | G protein-coupled receptors (GPCRs) are a large group of receptors of great biological and clinical relevance. Despite this, the tools for a detailed analysis of ligand-GPCR interactions are limited. The aim of this paper was to demonstrate how ligand binding to GPCRs can be followed in real-time on living cells. This was conducted using two model systems, the radiolabeled porcine peptide YY (pPYY) interacting with transfected human Y2 receptor (hY2R) and the bombesin antagonist RM26 binding to the naturally expressed gastrin-releasing peptide receptor (GRPR). By following the interaction over time, the affinity and kinetic properties such as association and dissociation rate were obtained. Additionally, data were analyzed using the Interaction Map method, which can evaluate a real-time binding curve and present the number of parallel interactions contributing to the curve. It was found that pPYY binds very slowly with an estimated time to equilibrium of approximately 12h. This may be problematic in standard end-point assays where equilibrium is required. The RM26 binding showed signs of heterogeneity, observed as two parallel interactions with unique kinetic properties. In conclusion, measuring binding in real-time using living cells opens up for a better understanding of ligand interactions with GPCRs. |
24211198 | Farnesoid X receptor up-regulates expression of lipid transfer inhibitor protein in liver cells and mice. | Apolipoprotein F is ponent protein mainly secreted by liver and resides on several lipoprotein classes. It can inhibit lipids transfer between different lipoproteins. FXR is a member of the nuclear receptor superfamily which is also highly expressed in the liver. It modulates bile acids synthesis and lipids metabolism by transcriptional regulation. We aimed to determine whether apoF can be regulated by FXR. The FXR agonist Chenodeoxycholic acid (CDCA) and GW4064 both can activate the expression of apoF in liver cell lines and in C57/BL6 mouse liver. This is dependent on the binding of FXR to the FXR element ER1 (-2904 to -2892 bp) in the apoF gene promoter. Taken together, we have identified apoF as likely another target gene of FXR. |
24211199 | Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. | LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using bination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal pared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations. |
24211194 | Entrance skin dosimetry and size-specific dose estimate from pediatric chest CTA. | Size-specific dose estimate (SSDE), which corrects CT dose index (CTDI) for body diameter and is a better measure of organ dose than is CTDI, has not yet been validated in vivo. |
24211200 | Sirt2 suppresses inflammatory responses in collagen-induced arthritis. | Arthritis is mon autoimmune disease that is associated with progressive disability, plications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD(+)-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis. |
24211201 | Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha. | (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha H16 (RePhaB) is an enzyme that catalyzes the NADPH-dependent reduction of acetoacetyl-CoA, an intermediate of polyhydroxyalkanoates (PHA) synthetic pathways. Polymeric PHA is used to make bioplastics, implant biomaterials, and biofuels. Here, we report the crystal structures of RePhaB apoenzyme and plex with either NADP(+) or acetoacetyl-CoA, which provide the catalytic mechanism of the protein. RePhaB contains a Rossmann fold and a Clamp domain for binding of NADP(+) and acetoacetyl-CoA, respectively. The NADP(+)-bound form of RePhaB structure reveals that the protein has a unique cofactor binding mode. Interestingly, in the RePhaB structure plex with acetoacetyl-CoA, the conformation of the Clamp domain, especially the Clamp-lid, undergoes a large structural change about 4.6 Å leading to formation of the substrate pocket. These structural observations, along with the biochemical experiments, suggest that movement of the Clamp-lid enables the substrate binding and ensures the acetoacetyl moiety is located near to the nicotinamide ring of NADP(+). |
24211202 | miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway. | Cardiomyocytes experience a series plex endogenous regulatory mechanisms against apoptosis induced by chronic hypoxia. MicroRNAs are a class of endogenous small non-coding RNAs that regulate cellular pathophysiological processes. Recently, microRNA-138 (miR-138) has been found related to hypoxia, and beneficial for cell proliferation. Therefore, we intend to study the role of miR-138 in hypoxic cardiomyocytes and the main mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected to test miR-138 expression. Agomir or antagomir of miR-138 was transfected into H9C2 cells to investigate its effect on cell apoptosis. Higher miR-138 expression was observed in patients with cyanotic CHD, and its expression gradually increased with prolonged hypoxia time in H9C2 cells. Using MTT and LDH assays, cell growth was significantly greater in the agomir group than in the negative control (NC) group, while antagomir decreased cell survival. Dual luciferase reporter gene and Western-blot results confirmed MLK3 was a direct target of miR-138. It was found that miR-138 attenuated hypoxia-induced apoptosis using TUNEL, Hoechst staining and Annexin V-PE/7-AAD flow cytometry analysis. We further detected expression of apoptosis-related proteins. In the agomir group, the level of pro-apoptotic proteins such as cleaved-caspase-3, cleaved-PARP and Bad significantly reduced, while Bcl-2 and Bcl-2/Bax ratio increased. Opposite changes were observed in the antagomir group. Downstream targets of MLK3, JNK and c-jun, were also suppressed by miR-138. Our study demonstrates that up-regulation of miR-138 plays a protective role in myocardial adaptation to chronic hypoxia, which is mediated mainly by MLK3/JNK/c-jun signaling pathway. |
24211203 | Anti-colorectal cancer activity of macrostemonoside A mediated by reactive oxygen species. | Macrostemonoside A (MSS.A), an active steroidal saponin from Allium macrostemon Bung has been shown to possess anti-coagulation and anti-obesity effects. However, the functional role of MSS.A on tumor growth has not been elucidated. We found that MSS.A significantly inhibited human colorectal cancer cell growth in Caco2 and SW480 cells. Incubation of SW480 cells with MSS.A for 48 h resulted in cell cycle arrest. Moreover, MSS.A dose-dependently induced apoptosis in SW480 cells as shown by increased AnnexinV positively stained cell population, caspase activation, increased pro-apoptotic and reduced anti-apoptotic Bcl-2 family protein levels. Treatment of SW480 cells with MSS.A resulted in increased reactive oxygen species (ROS) generation. However, pre-incubation of SW480 cells with antioxidant N-acetylcysteine (NAC) attenuated the ROS generation and anti-colorectal cancer activities of MSS.A. Lastly, intra-peritoneal injections of MSS.A significantly inhibited tumor formation in BALB/c nude mice carcinogenesis xenograft model by reduced tumor volume and tumor weight when treated at dosages of 10, 50 or 100mg/kg daily for 35 pared with PBS control. Taken together, our results indicate that MSS.A suppressed colorectal cancer growth and induced cell apoptosis by inducing ROS production, and that MSS.A may have therapeutic relevance in the treatment of human colorectal cancer. |
24211204 | Coxsackievirus A16 infection triggers apoptosis in RD cells by inducing ER stress. | Coxsackievirus A16 (CA16) infection, which is responsible for hand, foot and mouth disease (HFMD), has e mon health problem in Asia due to the prevalence of the virus. Thus, it is important to understand the pathogenesis of CA16 infection. Viruses that induce endoplasmic reticulum (ER) stress are confronted with the unfolded protein response (UPR), which may lead to apoptotic cell death and influence viral replication. In this study, we found that CA16 infection could induce apoptosis and ER stress in RD cells. Interestingly, apoptosis via the activation of caspase-3, -8 and -9 in the extrinsic or intrinsic apoptotic pathways in RD cells was inhibited by 4-phenyl butyric acid (4PBA), a chemical chaperone that reduces ER stress. These results suggest that CA16 infection leads to ER stress, which in turn results in prolonged ER stress-induced apoptosis. This study provides a new basis for understanding CA16 infection and host responses. |
24211205 | MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3. | The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR-124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3'-UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC. |
24211206 | Discovery of a disused desaturase gene from the pheromone gland of the moth Ascotis selenaria, which secretes an epoxyalkenyl sex pheromone. | Female Ascotis selenaria (Geometridae) moths use 3,4-epoxy-(Z,Z)-6,9-nonadecadiene, which is synthesized from linolenic acid, as the ponent of their sex pheromone. While the use of dietary linolenic or linoleic fatty acid derivatives as sex ponents has been observed in moth species belonging to a few families including Geometridae, the majority of moths use derivatives of mon saturated fatty acid, palmitic acid, as their sex ponents. We attempted to gain insight into the differentiation of pheromone biosynthetic pathways in geometrids by analyzing the desaturase genes expressed in the pheromone gland of A. selenaria. We demonstrated that a Δ11-desaturase-like gene (Asdesat1) was specifically expressed in the pheromone gland of A. selenaria in spite of the absence of a desaturation step in the pheromone biosynthetic pathway in this species. Further analysis revealed that the presumed transmembrane domains were degenerated in Asdesat1. Phylogenetic analysis demonstrated that Asdesat1 anciently diverged from the lineage of Δ11-desaturases, which are currently widely used in the biosynthesis of sex pheromones by moths. These results suggest that an ancestral Δ11-desaturase became dysfunctional in A. selenaria after a shift in pheromone biosynthetic pathways. |
24211207 | Sclerostin deficient mice rapidly heal bone defects by activating β-catenin and increasing intramembranous ossification. | We investigated the influence of the osteocyte protein, sclerostin, on fracture healing by examining the dynamics and mechanisms of repair of single-cortex, stabilized femoral defects in sclerostin knockout (Sost(-/-); KO) and sclerostin wild-type (Sost(+/+); WT) mice. Fourteen days following generation of bone defects, Sost KO mice had significantly more bone in the healing defect than WT mice. The increase in regenerating bone was due to an increase in the thickness of trabecularized spicules, osteoblast numbers and surfaces within the defect. Enhanced healing of bone defects in Sost KO mice was associated with significantly more activated β-catenin expression than observed in WT mice. The findings were similar to those observed in Axin2(-/-) mice, in which β-catenin signaling is known to be enhanced to facilitate bone regeneration. Taken together, these data indicate that enhanced β-catenin signaling is present in Sost(-/-) mice that demonstrate accelerated healing of bone defects, suggesting that modulation of β-catenin signaling in bone could be used to promote fracture repair. |
24211208 | Cholesterol glucosylation is catalyzed by transglucosylation reaction of β-glucosidase 1. | Cholesteryl glucoside (β-ChlGlc), a monoglucosylated derivative of cholesterol, is involved in the regulation of heat shock responses. β-ChlGlc, which is rapidly induced in response to heat shock, activates heat shock transcription factor 1 (HSF1) leading to the expression of heat shock protein 70 (HSP70) in human fibroblasts. Identification and biochemical characterization of the enzyme responsible for β-ChlGlc formation is important for plete understanding of the molecular mechanisms leading to HSP70-induction following heat shock. Recently, we demonstrated that β-ChlGlc synthesis is not dependent on UDP-Glucose but glucosylceramide (GlcCer) in animal tissue and human fibroblasts. In this study, we examined the possibility of glucocerebrosidase, a GlcCer-degrading glycosidase, acting as β-ChlGlc-synthesizing enzyme. Overexpression of β-glucosidase 1 (GBA1, lysosomal acid β-glucocerebrosidase) led to an increase in cholesterol glucosylation activity in human fibroblasts. Using a cell line generated from type 2 Gaucher disease patients with severe defects in GBA1 activity, we found that cholesterol glucosylation activity was very low in the cells and the overexpression of GBA1 rescued the activity. In addition, purified binant GBA1 exhibits conduritol B-epoxide-sensitive cholesterol glucosylation activity. The optimum pH and temperature for cholesterol glucosylation by GBA1 were at about 5.3 and 43 °C, respectively. Short chain C8:0-GlcCer was the most effective donor for cholesterol glucosylation activity among GlcCer containing saturated fatty acid (C8:0 to C18:0) tested. GlcCer containing mono-unsaturated fatty acid was more preferred substrate for cholesterol glucosylation pared with GlcCer containing same chain length of saturated fatty acid. These results demonstrate, for the first time, a novel function of GBA1 as a β-ChlGlc-synthesizing enzyme. Therefore, our results also reveal a new pathway for glycolipid metabolism in mammals. |
24211209 | SIRT1 suppresses cellular accumulation of β-TrCP E3 ligase via protein degradation. | β-Transducin repeat-containing protein (β-TrCP), an E3 ligase, promotes the degradation of substrate proteins in response to various stimuli. Even though several β-TrCP substrates have been identified to date, limited information of its upstream regulators is available. Here, we showed that SIRT1 suppresses β-TrCP protein synthesis via post-translational degradation. SIRT1 depletion led to a significant increase in the β-TrCP accumulation without affecting the mRNA level. Consistently, β-TrCP protein accumulation induced by resveratrol was further enhanced upon SIRT1 depletion. Rescue of SIRT1 reversed the effect of resveratrol, leading to reduced β-TrCP protein levels. Proteasomal inhibition led to recovery of β-TrCP in cells with SIRT1 overexpression. Notably, the recovered β-TrCP colocalized mostly with SIRT1. Thus, SIRT1 acts as a negative regulator of β-TrCP synthesis via promoting protein degradation. |
24211210 | Autocrine galectin-1 promotes collective cell migration of squamous cell carcinoma cells through up-regulation of distinct integrins. | We found that high galectin-1 (Gal-1) mRNA levels were associated with invasive squamous cell carcinoma (SCC) cells that expressed Snail, an epithelial-to-mesenchymal transition (EMT) regulator. Both Gal-1 overexpression and soluble Gal-1 treatment accelerated invasion and collective cell migration, along with activation of cdc42 and Rac. Soluble Gal-1 activated c-Jun N-terminal kinase to increase expression levels of integrins α2 and β5, which were essential for Gal-1 dependent collective cell migration and invasiveness. Soluble Gal-1 also increased the incidence of EMT in Snail-expressing SCC cells; these were a minor population with an EMT phenotype under growing conditions. Our findings indicate that soluble Gal-1 promotes invasiveness through enhancing collective cell migration and increasing the incidence of EMT. |
24211211 | The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast. | Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions. |
24211212 | AT1 receptor blocker potentiates shear-stress induced nitric oxide production via modulation of eNOS phosphorylation of residues Thr(495) and Ser(1177.). | We tested the hypothesis that AT1R blockade modulates the shear stress-induced (SS) synthesis of nitric oxide (NO) in endothelial cells (EC). The AT1R blocker Candesartan in the absence of the ligand angiotensin II (ang II) potentiated SS-induced NO synthesis panied by increased p-eNOS(Ser1177) and decreased p-eNOS(Thr495). Candesartan also inhibited SS-induced ERK activation and increased intracellular calcium transient in a time-dependent manner. To confirm the role of ERK to modulate p-eNOS(Thr495) and calcium to modulate p-eNOS(Ser1177), the MEK inhibitor U0126 and the calcium chelator BAPTA-AM were used, respectively. Pre-treatment of EC with pleted abrogated basal and SS-induced ERK activation, inhibited p-eNOS(Thr495) and increased NO production by SS. On the other hand, pre-treatment of EC with BAPTA-AM decreased the effects of SS alone or bination with Candesartan to induce p-eNOS(Ser1177) and partially inhibited the effects of Candesartan to potentiate NO release by SS. The AT1R blockers Losartan and Telmisartan were also tested but only Telmisartan potentiated NO synthesis and blocked SS-induced AT1R activation. Altogether, we provide evidence that Candesartan and Telmisartan potentiate SS-induced NO production even in the absence of the ligand ang II. This response requires both the inhibition of eNOS phosphorylation at its inhibitory residue Thr(495) as well as the increase of eNOS phosphorylation at its excitatory residue Ser(1177). In addition, the response is associated with inhibition of SS-induced ERK activation as well as increasing intracellular calcium transient. One may speculate that these yet undescribed events may contribute to the benefits of ARBs in cardiovascular diseases. |
24211213 | Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate. | Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. paring crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine-143 was found to be exposed more than 60Å(2) to the solvent in F-actin. Because tyrosine-143 flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins parable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be pared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (Vmax) were estimated by a double reciprocal plot. The Tyr143Trp-actin showed the higher affinity (smaller Kapp) than that of the wild-type actin, with the Vmax being almost unchanged. The Kapp and Vmax of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of Kapp was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas (ASA) of the replaced amino acid molecule. Because 1/Kapp reflects the affinity of F-actin for the myosin-ADP-phosphate intermediate (M.ADP.Pi) through the weak binding, these data suggest that the bulkiness or the aromatic nature of the tyrosin-143 is important for the initial binding of the M.ADP.Pi intermediate with F-actin but not for later processes such as the phosphate release. |
24211214 | Let's not forget the thinkers. | As 'omics' technologies e more accessible, enormous quantities of data are being generated about the genomes, proteomes, metabolomes, etc. of an increasing number of parasites. We therefore need to think very carefully about how these resources will contribute to our basic understanding of parasitism, and beyond the 'knee-jerk' es of new vaccines and therapeutics. The lasting legacy of the 'omics' era may lie in addressing the fundamental biological hypotheses generated by parasitologists 40-50 years ago when direct observational studies were a feature of parasitological research. We illustrate this with reference to the cestode parasite Echinococcus and the far-reaching questions posed by Desmond Smyth. |
24211216 | Heterosandwich immunoswab assay for dengue virus Ns1 antigen detection. | Dengue and the more severe dengue hemorrhagic fever have been a very critical public health problem globally. Millions of people especially in the tropical areas get infected with dengue. An efficient diagnostic is very important for early screening of dengue infection. In dengue-infected patients, the nonstructural protein NS1 is present on the surface of infected cells and secreted in plasma. The NS1 antigen is an important target for developing a quick diagnostic largely due to its long presence in the blood. We have developed a simple-to-use immunoswab-based diagnostic procedure employing monoclonal antibodies and the second-generation quadromas. The detection limit for NS1 has been established to be in the subnanogram range. The assay is very sensitive, has a visual end point, and also being extremely inexpensive. With this assay, screening time for a dengue-infected person would be very rapid. |
24211217 | Panton-Valentine leukocidin (PVL) gene carriage among Staphylococcus aureus strains with SCCmec types I, III, IV, and V recovered from cystic fibrosis pediatric patients in Brazil. | The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in patients with cystic fibrosis (CF). We report a molecular characterization, antimicrobial resistance, and Panton-Valentine leukocidin (PVL) toxin gene detection of MRSA strains from 28 Brazilian pediatric CF patients (1 strain per patient). A significant proportion (50%) of MRSA SCCmec IV isolates was observed. Nearly half of MRSA strains harboring the PVL genes distributed in all SCCmec types detected. Multilocus sequence typing (MLST) analyses showed majority (57.1%) of the isolates belonged to known epidemic lineages, such as UK/EMRSA-3, Pediatric/USA 800, Southwest Pacific clone, and Brazilian/Hungarian clone. To our knowledge, this is the first Brazilian study of molecular epidemiology based on MLST and SCCmec typing and the first description of PVL genes in MRSA from CF patients. |
24211218 | Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: predominance of KPC-2 enzyme. | Among 228 carbapenem-nonsusceptible Enterobacteriaceae isolated in China, 65 were carbapenemase-producing Enterobacteriaceae (CPE). Among them, 41, 22, 1, and 1 produced KPC-2, IMP-4, IMP-8, and IMP-1, respectively. KPC-2-producing CPE showed higher resistance than IMP-4-producing ones. Furthermore, the first outbreak of ST11 KPC-2-producing Klebsiella pneumoniae in a Beijing second-degree hospital was identified. |
24211220 | Association of umbilical cord plasma acid-labile subunit of the insulin-like growth factor ternary complex with anthropometry in term newborns. | Birth size can affect neonatal morbidity and mortality. The insulin-like growth factor (IGF) system is the most important endocrine factor influencing fetal growth. In the circulation, IGFs (mostly IGF-I) are bound to IGF-binding protein 3 (IGFBP-3) and an acid-labile subunit (ALS) to form a plex. The ALS protects IGFs from decay and facilitates their endocrine activity. However, the function of ALS in fetal growth has not yet been fully determined. |
24211221 | Statistical method for prediction of gait kinematics with Gaussian process regression. | We propose a novel methodology for predicting human gait pattern kinematics based on a statistical and stochastic approach using a method called Gaussian process regression (GPR). We selected 14 body parameters that significantly affect the gait pattern and 14 joint motions that represent gait kinematics. The body parameter and gait kinematics data were recorded from 113 subjects by anthropometric measurements and a motion capture system. We generated a regression model with GPR for gait pattern prediction and built a stochastic function mapping from body parameters to gait kinematics based on the database and GPR, and validated the model with a cross validation method. The function can not only produce trajectories for the joint motions associated with gait kinematics, but can also estimate the associated uncertainties. Our approach results in a novel, low-cost and subject-specific method for predicting gait kinematics with only the subject's body parameters as the necessary input, and also enables prehensive understanding of the correlation and uncertainty between body parameters and gait kinematics. |
24211222 | Interictal serum S-100B protein levels in intractable epilepsy: a case-control study. | Epilepsy is the mon neurologic disorder of childhood. In approximately 6-14% of all patients with plete seizure control is difficult to achieve with current antiepileptic treatments. Several current studies have shown in both animals and people that the lengthening of epileptic seizures and frequent recurrence increases the likelihood of neuronal damage. S-100B protein is the most analyzed brain derived peripheral biochemical marker in brain damage. This study aimed to evaluate interictal serum S-100B protein levels in children diagnosed with intractable epilepsy. A group of 32 patients with intractable epilepsy and 25 healthy controls were recruited. Serum S-100B protein levels were measured using mercially available electrochemiluminescence immunoassay (ECLIA kit, as supplied and according to the manufacturer's standards. The serum S-100B protein levels of the patient group in the study were found to be 0.094±0.011 μm/L, and 0.083±0.014 μm/L in the age-matched control group. The difference between the groups was determined to be statistically significant (P=0.004). In conclusions, it can be said that as the serum S-100B protein levels of the patients with focal epilepsy were pared to those of the control group, this can be reliable peripheral biomarker for neuronal damage in patients with focal intractable epilepsy. |
24211223 | Using fMRI virtual-reality technology to predict driving ability after brain damage: a preliminary report. | The cerebellum, which is important for movement control and planning, is often affected by many neurological conditions. Until now there has been limited information regarding how the function of the cerebellum impacts driving ability. This study used fMRI with an integrated virtual reality driving simulator to determine which aspects of driving performance are related to the cerebellum in healthy drivers (Experiment 1). It also investigated drivers with focal cerebellar lesions to identify how damage to this brain region impairs driving abilities. The results showed that cerebellar functioning is responsible for motor-speed coordination plex temporal-motor integration necessary to execute driving behaviours. As predicted, drivers with cerebellar damage, showed promised speed control during basic driving conditions, whereas their ability to perform during interactive driving situations was preserved. New insights into neural mechanisms and brain plasticity regarding driving behaviour are discussed. Strategies in assessing and rehabilitating drivers with related neurological conditions are provided. |
24211224 | S100B as a glial cell marker in diabetic peripheral neuropathy. | Evidence suggests that acute and chronic hyperglycemia can cause oxidative stress in the peripheral nervous system which, in turn, can promote the development of diabetic neuropathy. Recent studies have found increased expression of glial fibrillary acidic protein (GFAP) and S100B, both of which are indicators of glial reactivity, in the neural and retinal tissues of diabetic rats. For the first time in the literature, the serum levels of GFAP and S100B were assessed in patients with diabetes to evaluate the potential of these factors to serve as peripheral glial biomarkers of diabetes and to investigate their relationship to diabetic peripheral neuropathy. This prospective clinical study included 72 patients with type 2 diabetes mellitus and 50 age- and sex-matched control subjects. All diabetic patients were assessed with respect to diabetes-related plications, such as peripheral neuropathy, retinopathy, and nephropathy. Serum samples were analyzed for human GFAP and S100B using mercially available Enzyme-linked Immuno Sorbent Assay kit. GFAP was not detected in the serum samples of either diabetic or control patients (p>0.05). However, we found a statistically significant decrease in S100B serum levels in patients with pared with control participants (p<0.001). No associations between serum S100B levels and the presence of diabetic peripheral neuropathy or other plications were observed (p>0.05). The findings of markedly decreased serum levels of S100B may possibly indicate a neuroprotective effect of S100B, whereas GFAP may be of no diagnostic value in human patients with diabetes. |
24211226 | Imported strongyloidiasis in Spain. | The objective of this study was to assess the epidemiological, laboratory, and clinical features of imported strongyloidiasis in a tropical medicine referral unit in Madrid, Spain. |
24211228 | Bilharzia in the Philippines: past, present, and future. | Schistosomiasis japonica has a long history in the Philippines. In 1975, 24 endemic provinces were identified in the northern, central, and southern islands of the Philippines. More than five million people were at risk, with approximately one million infected. In 2003, new foci of infection were found in two provinces in the north and central areas. For the past 30 years, human mass drug administration (MDA), utilizing the drug praziquantel, has been the mainstay of control in the country. Recent studies have shown that the schistosomiasis prevalence ranges from 1% to 50% within different endemic zones. Severe end-organ morbidity is still present in many endemic areas, particularly in remote villages with poor treatment coverage. Moreover, subtle morbidities such as growth retardation, malnutrition, anemia, and poor cognitive function in infected children persist. There is now strong evidence that large mammals (e.g. water buffaloes, cattle) contribute significantly to disease plicating control efforts. Given the zoonotic nature of schistosomiasis in the Philippines, it is evident that the incidence, prevalence, and morbidity of the disease will not be controlled by MDA alone. There is a need for innovative cost-effective strategies to control schistosomiasis in the long term. |
24211227 | Mortality indicators in pneumococcal meningitis: therapeutic implications. | The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. |
24211229 | Classification of incidence and prevalence of certain sexually transmitted infections by world regions. | This study sought to assess if there is a meaningful way in which variations in sexually transmitted infection (STI) prevalence can be classified at the level of world regions. |
24211230 | Community-acquired pneumonia and tuberculosis: differential diagnosis and the use of fluoroquinolones. | The respiratory fluoroquinolones moxifloxacin, gemifloxacin, and high-dose levofloxacin are mended in guidelines for effective empirical antimicrobial therapy munity-acquired pneumonia (CAP). The use of these antibiotics for this indication in areas with a high prevalence of tuberculosis (TB) has been questioned due to the perception that they contribute both to delays in the diagnosis of pulmonary TB and to the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis. In this review, we consider some of the important questions regarding the potential use of fluoroquinolones for the treatment of CAP where the burden of TB is high. The evidence suggests that the use of fluoroquinolones as mended for 5-10 days as empirical treatment for CAP, according to current clinical management guidelines, is appropriate even in TB-endemic regions. It is critical to quickly exclude M. tuberculosis as a cause of CAP using the most rapid relevant diagnostic investigations in the management of all patients with CAP. |
24211231 | Treatment experiences of pelvic bone hydatidosis. | Hydatid diseases of the pelvic bone are rare, generally incurable, and have high rates of recurrence. |
24211232 | Fluorescence in situ hybridization panel for monitoring of minimal residual disease in patients with double minute chromosomes. | A double minute chromosome (dmin) is a small fragment of extrachromosomal DNA bearing amplified genes observed in malignancies. We investigated the incidence and characteristics of dmins in hematologic malignancies, and the quantitative changes during the treatment follow-up. Once a dmin was observed in conventional G-banding, it was characterized using fluorescence in situ hybridization (FISH) with the panel of MYC, NMYC, and MLL probes. Quantitative changes of malignant cells were measured using G-banding and FISH during the follow up. Dmins were observed in 1.23% of patients (6/489) at the initial diagnosis including 4 with MYC amplification, 1 with MLL and 1 with NMYC. All 6 plex karyotypes and showed short overall survival (7.7 months). In follow-up specimens, FISH detected dmins in 11 cases out of which G-banding detected dmins in 9 cases. The number of dmins detected by FISH and G-banding did not correlate well. Amplification of NMYC in dmins is reported for the first time. A FISH posed of frequently amplified oncogenes (MYC, NMYC, and MLL) in dmins is useful for characterization of dmins. FISH is a sensitive method in detecting dmins and will be useful in monitoring of the minimal residual disease. |
24211233 | Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1β induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes. | Interleukin-1β (IL-1β) is involved in the up-regulation of matrix metalloproteinases (MMPs) leading to cartilage degradation. Cannabinoids are anti-inflammatory and reduce joint damage in animal models of arthritis. This study aimed to determine a mechanism whereby the synthetic cannabinoid WIN-55,212-2 mesylate (WIN-55) may inhibit cartilage degradation. |
24211234 | Structural determinants of unique properties of human IgG4-Fc. | Human IgG4, normally the least abundant of the four subclasses of IgG in serum, displays a number of unique biological properties. It can undergo heavy-chain exchange, also known as Fab-arm exchange, leading to the formation of monovalent but bispecific antibodies, and it interacts poorly with FcγRII and FcγRIII, plement. These properties render IgG4 relatively "non-inflammatory" and have made it a suitable format for therapeutic monoclonal antibody production. However, IgG4 is also known to undergo Fc-mediated aggregation and has been implicated in auto-immune disease pathology. We report here the high-resolution crystal structures, at 1.9 and 2.35 Å, respectively, of human binant and serum-derived IgG4-Fc. These structures reveal conformational variability at the CH3-CH3 interface that may promote Fab-arm exchange, and a unique conformation for the FG loop in the CH2 domain that would explain the poor FcγRII, FcγRIII and C1q binding properties of pared with IgG1 and -3. In contrast to other IgG subclasses, this unique conformation folds the FG loop away from the CH2 domain, precluding any interaction with the lower hinge region, which may further facilitate Fab-arm exchange by destabilisation of the hinge. The crystals of IgG4-Fc also display Fc-Fc packing contacts with very extensive interaction surfaces, involving both a consensus binding site in IgG-Fc at the CH2-CH3 interface and known hydrophobic aggregation motifs. These Fc-Fc interactions patible with intact IgG4 molecules and may provide a model for the formation of aggregates of IgG4 that can cause disease pathology in the absence of antigen. |
24211235 | Altered expression of 5-HT1A receptors in adult rats induced by neonatal treatment with clomipramine. | Chronic administration of clomipramine (CMI) to neonatal rats produces behaviors that resemble a depressive state in adulthood. Dysfunctions in the activity of the central nervous system's serotonergic function are important in understanding the pathophysiology of depression. The serotonin system is implicated in major depression and suicide and is negatively regulated by somatodendritic 5-HT1A autoreceptors. Desensitization of 5-HT1A autoreceptors is implicated in the long latency of some antidepressant treatments. Alterations in 5-HT1A receptor levels are reported in depression and suicide. In this study, we analyzed the effect of neonatal administration of CMI on the activity of 5-HT1A receptors, both pre- and post-synaptically, by administering an agonist of 5-HT1A receptors, 8-OH-DPAT, and then subjecting the rats to the forced swimming test (FST) mon procedure used to detect signs of depression in rats. Also measured were levels of the mRNA expression of 5-HT1A receptors in the dorsal raphe (DR), the hypothalamus and the hippocampus. Wistar rats were injected twice daily with CMI at doses of 15mgkg(-1) or saline as vehicle (CON) via s.c. from postnatal day 8 for 14days. At 3-4months of age, one set of rats from each group (CON, CMI) was evaluated for the effect of a selective agonist to the 5-HT1A receptor subtype, 8-OH-DPAT, by testing in the FST. Also determined was the participation of the pre- or post-synaptic 5-HT1A receptor in the antidepressant-like action of 8-OH-DPAT. This involved administering an inhibitor of tryptophan hydroxylase, parachlorophenylalanine (PCPA), and pretreatment with 8-OH-DPAT before the FST test and to evaluate the rectal temperature and otor activity. The expression of the mRNA of the 5-HT1A receptors was examined in the dorsal raphe nucleus, the hypothalamus and the hippocampus using the semi-quantitative RT-PCR method. The results from this study corroborate that neonatal treatment with clomipramine induces a pronounced immobility in the FST when animals reach adulthood, manifested by a significant decrease in swimming behavior, though counts of climbing behavior were not modified. This effect was similar in magnitude when 8-OH-DPAT was administered to CON group. Furthermore, the administration of 8-OH-DPAT induces a significant and similar increase in rectal temperature and otor activity in both the CON as in the CMI group. Neonatal treatment with CMI resulted in a significant decrease in the expression of the mRNA of the 5-HT1A receptors in the DR (% more than vehicle) in adulthood. In the case of the postsynaptic receptors located in the hypothalamus and hippocampus, neonatal treatment with CMI induced a significant increase in the mRNA expression of the 5-HT1A receptors. These data suggest that neonatal treatment with CMI induces a downregulation of the mRNA of the 5-HT1A autoreceptors in the DR, and an increment in the expression of the postsynaptic 5-HT1A receptors. The results after the administration of PCPA and 8-OH-DPAT on FST, rectal temperature and otor activity for both groups suggest that the function of postsynaptic receptors remains unchanged. All together these data show that the depressive behavior observed in adulthood in this animal model may be associated with long-term alterations in the expression of the mRNA of the 5-HT1A receptors. |
24211236 | Impaired inhibition after total sleep deprivation using an antisaccade task when controlling for circadian modulation of performance. | Sleep deprivation affects several cognitive functions subserved by the prefrontal cortex. Conflicting results have, nonetheless, been reported for inhibitory function, which could be explained by methodological bias. The present study aimed to assess the effects of sleep deprivation on response inhibition using a particularly suitable inhibition test, the antisaccade, while controlling for circadian influences on performance. For this purpose, testing was conducted at: (1) the same time of day in both the control and sleep deprivation conditions; and (2) at a time of day when inhibitory performance has been found not to be at its lowest level. Two other neuropsychological tasks (go no-go and patibility) were used parison. |
24211237 | Effect of dopamine D1 and D2 receptor antagonism in the lateral hypothalamus on the expression and acquisition of fructose-conditioned flavor preference in rats. | The attraction to sugar-rich foods is influenced by conditioned flavor preferences (CFP) produced by the sweet taste of sugar (flavor-flavor learning) and the sugar's post-oral actions (flavor-nutrient) learning. Brain dopamine (DA) circuits are involved in both types of flavor learning, but to different degrees. This study investigated the role of DA receptors in the lateral hypothalamus (LH) on the flavor-flavor learning produced the sweet taste of fructose. In an acquisition study, food-restricted rats received bilateral LH injections of a DA D1 receptor antagonist (SCH23390), a D2 antagonist (RAC, raclopride) or vehicle prior to 1-bottle training sessions with a flavored 8% fructose+0.2% saccharin solution (CS+/F) and a less-preferred flavored 0.2% saccharin solution (CS-). Drug-free 2-bottle tests were then conducted with the CS+ and CS- flavors presented in saccharin. The fructose-CFP did not differ among groups given vehicle (76%), 12 nmol SCH (78%), 24 nmol (82%) or 24 nmol RAC (90%) during training. In an expression study with rats trained drug-free, LH injections of 12 or 24 nmol SCH or 12-48 nmol RAC prior to 2-bottle tests did not alter CS+ preferences (77-90%) relative to vehicle injection (86%). Only a 48 nmol SCH dose suppressed the CS+ preference (61%). The minimal effect of LH DA receptor antagonism upon fructose flavor-flavor conditioning differs with the ability of LH SCH injections to block the acquisition of glucose flavor-nutrient learning. |
24211239 | Travel and non-travel associated rabies post exposure treatment in New South Wales residents, Australia, 2007-2011: a cross-sectional analysis. | Australian Bat Lyssavirus is endemic in Australian bats. More Australians are travelling to rabies (Lyssavirus 1) endemic countries. The nature and frequency of lyssavirus exposures and characteristics of New South Wales (NSW) residents exposed have not previously been described. |
24211243 | Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression. | KIT inhibition with dasatinib represents a promising approach to targeted therapy in t(8;21) acute myeloid leukemia (AML) and clinical trials are currently evaluating its clinical relevance. However, data on continuous long-term dasatinib exposure of AML cells are limited and the potential effects on KIT inhibition and dasatinib sensitivity are unexplored. Treatment-related resistance ultimately limits clinical efficacy of tyrosine kinase inhibitors (TKI), which could similarly apply to dasatinib in t(8;21) AML. In this study, we used the dasatinib-sensitive KIT(mut) t(8;21) AML cell line Kasumi-1 to model, in a confined and controllable way, molecular effects upon continuous dasatinib treatment. Long-term dasatinib exposure at clinically relevant levels resulted in markedly decreased drug-sensitivity of KIT(mut) t(8;21) AML cells. Notably, all dasatinib-resistant clones lacked secondary KIT-mutations. Instead, persistent growth correlated with alterations in KIT expression levels-that is, either KIT overexpression with maintained downstream signaling or KIT downregulation with itant activation of alternate pathways. Although KIT overexpression was associated with retained receptor activity and STAT3 activation, KIT downregulation correlated with decreased STAT3 levels and increased ERK-signaling. Importantly, brief discontinuation of dasatinib restored dasatinib-sensitivity associated with reversal of signaling signatures similar to treatment-naive, dasatinib-sensitive cells. The observed desensitization of KIT(mut) t(8;21) AML cells upon continuous dasatinib exposure suggests that therapy-related acquisition of resistance could pose significant limitations on therapeutic efficiency. Notably, we identified TKI-resistant states of transient nature that correlate with alterations in KIT expression and can be reversed upon brief inhibitor withdrawal. These findings indicate that discontinuing treatment maintains dasatinib sensitivity in KIT(mut) AML cells. |
24211240 | Tungiasis - A Janus-faced parasitic skin disease. | Tungiasis is a parasitic skin disease caused by the penetration of female sand fleas (Tunga penetrans). It is acquired when people walk barefoot or rest on soil, where sand fleas pleted the off-host cycle. Tungiasis is a classic poverty-associated disease which belongs to the family of neglected tropical diseases (NTD). It has a Janus-face: while in travellers tungiasis usually is a benign self-limiting skin disease, inhabitants of endemic areas suffer from heavy infestations and severe, frequently debilitating and incapacitating morbidity. We describe the epidemiological and clinical characteristics of travel-associated tungiasis pare these features to the situation in munities in South America and sub-Saharan Africa. |
24211244 | Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep. | The pound triclabendazole (TCBZ) has plex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10mg/kg). At 3, 24, 48 and 60h post-treatment (pt), animals were sacrificed (n=3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8μg/mL (TCBZ.SO) and 12.6μg/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35μg/g (TCBZ.SO) and 13.9μg/g (TCBZ.SO2) at 24h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14μg/g at 24h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1μg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the pound accumulated in liver tissue over the 60h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites. However, the presence of TCBZ within the adult fluke (despite being absent in the systemic circulation) may be related to some degree of trans-tegumental diffusion from bile or by a direct oral ingestion from portal blood. |
24211245 | Progress on retinal image analysis for age related macular degeneration. | Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used bination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine bination puter-aided analysis for large munities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and puter-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which include diagnosis and management of AMD, and how automated disease grading could benefit telemedicine. As there is no treatment for dry AMD and only early intervention can prevent the late AMD, we emphasize mass screening through a telemedicine platform to enable early detection of AMD. We also provide parative study between the imaging modalities and identify potential study areas for further improvement and future research direction in automated AMD grading and screening. |
24211241 | Imported Armillifer pentastomiasis: report of a symptomatic infection in The Netherlands and mini-review. | We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year-old female Liberian immigrant to The Netherlands. The patient was referred to the gynecologist because of lower abdominal pain. During laparotomy, multiple adhesions were seen in the lower pelvis and a hydrosalpinx with an encapsulated Armillifer nymph, most likely Armillifer armillatus, was found. Key features of the parasite's cuticle which facilitate the diagnosis of pentastomiasis, are presented. Symptomatic pentastomiasis is mon, and most cases are diagnosed incidentally during surgery for other reasons, or at autopsy. With regard to increasing international migration, other imported pentastomiasis cases to Europe and North America are reviewed, and more cases are likely to be seen in the future. |
24211246 | Nature-via-nurture and unravelling causality in evolutionary genetics. | Quantitative geneticists traditionally attribute phenotypic variation to genetic or environmental sources. New findings with near-clonal mice raised in a single enriched environment demonstrated significant developmental and behavioural divergence. This suggests intriguing possibilities for how (epi)genomes and environments might interact to drive phenotypic individuality, thus shaping evolutionary pathways. |
24211248 | Influence of glenoid component design and humeral component retroversion on internal and external rotation in reverse shoulder arthroplasty: a cadaver study. | mon disadvantage of reverse shoulder arthroplasty is limitation of the range of arm rotation. Several changes to the prosthesis design and implantation technique have been suggested to improve rotation range of motion (ROM). |
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