Dataset Viewer
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37410464
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Naloxone Accessibility Under the State Standing Order Across Mississippi.
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Importance
Naloxone is a life-saving medication for individuals experiencing an opioid overdose. Naloxone standing orders aim to make naloxone more available by allowing patients improved access to this medication at community pharmacies; however, lawful availability does not mean that this life-saving intervention is accessible to patients.
Objective
To characterize naloxone availability and out-of-pocket cost under the state standing order in Mississippi.
Design, Setting, and Participants
This telephone-based, mystery-shopper census survey study included Mississippi community pharmacies open to the general public in Mississippi at the time of data collection. Community pharmacies were identified using the Hayes Directories April 2022 complete Mississippi pharmacy database. Data were collected from February to August 2022.
Exposures
Mississippi House bill 996, the Naloxone Standing Order Act, signed into law in 2017, allowing pharmacists to dispense naloxone under a physician state standing order at a patient's request.
Main Outcomes and Measures
The main outcomes were naloxone availability under Mississippi's state standing order and the out-of-pocket cost of available formulations.
Results
There were 591 open-door community pharmacies surveyed for this study, with a 100% response rate. The most common pharmacy type was independent (328 [55.50%]), followed by chain (147 [24.87%]) and grocery store (116 [19.63%]). When asked, "Do you have naloxone that I can pick up today?" 216 Mississippi pharmacies (36.55%) had naloxone available for purchase under the state standing order. Of the 591 pharmacies, 242 (40.95%) were unwilling to dispense naloxone under the state standing order. Among the 216 pharmacies with naloxone available, the median out-of-pocket cost for naloxone nasal spray (n = 202) across Mississippi was $100.00 (range, $38.11-$229.39; mean [SD], $105.58 [$35.42]) and the median out-of-pocket cost of naloxone injection (n = 14) was $37.70 (range, $17.00-$208.96; mean [SD], $66.62 [$69.27]).
Conclusions and Relevance
In this survey study of open-door Mississippi community pharmacies, availability of naloxone was limited despite standing order implementation. This finding has important implications for the effectiveness of the legislation in preventing opioid overdose deaths in this region. Further studies are needed to understand pharmacists' unwillingness to dispense naloxone and the implications of lack of availability and unwillingness for further naloxone access interventions.
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37410465
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Effect of Risk-Stratified Care on Disability Among Adults With Low Back Pain Treated in the Military Health System: A Randomized Clinical Trial.
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Importance
Tailored treatments for low back pain (LBP) based on stratifying risk for poor prognosis have emerged as a promising approach to improve quality of care, but they have not been validated in trials at the level of individual randomization in US health systems.
Objective
To assess the clinical effectiveness of risk-stratified vs usual care on disability at 1 year among patients with LBP.
Design, Setting, and Participants
This parallel-group randomized clinical trial enrolled adults (ages 18-50 years) seeking care for LBP with any duration in primary care clinics within the Military Health System from April 2017 to February 2020. Data analysis was conducted from January to December 2022.
Interventions
Risk-stratified care, in which participants received physiotherapy treatment tailored for their risk category (low, medium, or high), or usual care, in which care was determined by participants' general practitioners and may have included a referral to physiotherapy.
Main Outcomes and Measures
The primary outcome was the Roland Morris Disability Questionnaire (RMDQ) score at 1 year, with planned secondary outcomes of Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) and Physical Function (PF) scores. Raw downstream health care utilization was also reported within each group.
Results
Analysis included 270 participants (99 [34.1%] female participants; mean [SD] age, 34.1 [8.5] years). Only 21 patients (7.2%) were classified as high risk. Neither group was superior on the RMDQ (least squares [LS] mean ratio of risk-stratified vs usual care: 1.00; 95% CI, 0.80 to 1.26), the PROMIS PI (LS mean difference, -0.75 points; 95% CI -2.61 to 1.11 points), or the PROMIS PF (LS mean difference, 0.05 points; 95% CI, -1.66 to 1.76 points).
Conclusions and Relevance
In this randomized clinical trial, using risk stratification to categorize and provide tailored treatment for patients with LBP did not result in better outcomes at 1 year compared with usual care.
Trial Registration
ClinicalTrials.gov Identifier: NCT03127826.
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37410466
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Psychiatric Boarding Patterns Among Publicly Insured Youths Evaluated by Mobile Crisis Teams Before and During the COVID-19 Pandemic.
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Importance
Psychiatric boarding occurs when patients needing intensive psychiatric services who are already under clinical supervision experience delays in their admission to psychiatric facilities. Initial reports have suggested that the US had a psychiatric boarding crisis during the COVID-19 pandemic; however, little is known about the consequences of this crisis for publicly insured youths.
Objective
To estimate pandemic-associated changes in psychiatric boarding rates and discharge modalities for people aged 4 to 20 years who accessed psychiatric emergency services (PES) through a mobile crisis team (MCT) evaluation and were covered by Medicaid or health safety net programs.
Design, Setting, and Participants
This retrospective cross-sectional study used data from the MCT encounters of a multichannel PES program in Massachusetts. A total of 7625 MCT-initiated PES encounters with publicly insured youths who lived in Massachusetts between January 1, 2018, and August 31, 2021, were assessed.
Main Outcomes and Measures
Encounter-level outcomes (psychiatric boarding status, repeat visits, and discharge disposition) during a prepandemic period (January 1, 2018, to March 9, 2020) were compared with outcomes during a pandemic period (March 10, 2020, to August 31, 2021). Descriptive statistics and multivariate regression analysis were used.
Results
Among 7625 MCT-initiated PES encounters, the mean (SD) age of publicly insured youths was 13.6 (3.7) years; most youths identified as male (3656 [47.9%]), were of Black race (2725 [35.7%]) or Hispanic ethnicity (2708 [35.5%]), and spoke English (6941 [91.0%]). During the pandemic period, the mean monthly boarding encounter rate was 25.3 percentage points higher than the prepandemic period. After adjustment for covariates, the odds of an encounter resulting in boarding doubled during the pandemic (adjusted odds ratio [AOR], 2.03; 95% CI, 1.82-2.26; P < .001), and boarding youths were 64% less likely to be discharged to inpatient psychiatric care (AOR, 0.36; 95% CI, 0.31-0.43; P < .001). Publicly insured youths who boarded during the pandemic had significantly higher rates of 30-day readmissions (incidence rate ratio, 2.17; 95% CI, 1.88-2.50; P < .001). Boarding encounters during the pandemic were significantly less likely to end in discharge to inpatient psychiatric units (AOR, 0.36; 95% CI, 0.31-0.43; P < .001) or community-based acute treatment facilities (AOR, 0.70; 95% CI, 0.55-0.90; P = .005).
Conclusions and Relevance
In this cross-sectional study, publicly insured youths were more likely to experience psychiatric boarding during the COVID-19 pandemic and, if boarding, were less likely to transfer to a 24-hour level of care. These findings suggest that psychiatric service programs for youths were not prepared to support the levels of acuity and demand that emerged from the pandemic.
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37775691
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The Social Dynamics of Fun: Can Fun Youth Bring Peers Together and Positively Influence Their Friends?
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There is a critical gap in our understanding of how peer relationships contribute to positive youth development. To address this gap the current study uses longitudinal social network data to examine if fun youth were socially desirable, inclusive of peers, and positive agents of social influence during the transition to adolescence. Participants were 210 students (47% female; Mage = 11.55 years at the outset) from 8 classes in 3 schools in a small Lithuanian city. Each child received a fun score consisting of nominations from classmates as "someone who is fun to be around". Participants also nominated up to five classmates as friends. Fun students received more friendship nominations than their peers and they maintained higher levels of social desirability over time. Fun youth appeared to be inclusive of their peers in that fun youth did not appear to have preferences to befriend only those like themselves. The friends of fun youth were positively influenced such that they were perceived to be more fun over time. The findings suggests that fun youth may promote positive social change within peer groups.
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37775692
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Navigating Across Heritage and Destination Cultures: How Personal Identity and Social Identification Processes Relate to Domain-Specific Acculturation Orientations in Adolescence.
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Personal identity and social identification processes can be challenging for adolescents belonging to an ethnic minority, who have to cope with the acculturation task of navigating several (and often conflictual) alternatives put forth by their cultural heritage community and destination society. Because identity and acculturation tasks are embedded in core domains of adolescents' life, this three-wave longitudinal study with ethnic minority adolescents (N = 244, 43.4% male; Mage = 14.9) examined how personal identity processes and social identifications are related to acculturation orientations in the education and friendship domains. Results of traditional cross-lagged models showed that, in the educational domain, adolescents who scored higher on cultural heritage maintenance compared to their peers, scored higher on commitment later on. In the friendship domain, stronger associations were found, such that adolescents who scored higher on cultural heritage maintenance compared to their peers, reported higher commitment and in-depth exploration later on, while those who scored higher on identification with friends reported over time also higher cultural heritage maintenance and destination culture adoption. Random-intercept crossed-lagged models indicated that, when adolescents reported above their own average on reconsideration of educational commitment, they reported increased cultural heritage maintenance later on. Furthermore, consistent associations (at baseline and over time) emerged. Overall, this study points to virtuous alliances between the fulfillment of tasks related to adolescents' identity development and acculturation.
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37775703
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Assessment of Ante- and Postnatal Development of the Offspring of Male Rats Crossed in Delayed Periods after Treatment with Methotrexate in Low Doses.
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We studied ante- and postnatal development of the offspring of intact female rats crossed with males injected with low doses of methotrexate 3 and 6 months before mating. The time of crossing corresponded to the manifestation of the cytostatic effect on spermatogonial stem cells. The offspring of methotrexate-treated males was characterized by increased preimplantation losses and fetal growth restriction in the antenatal period and inhibition of physical development, delayed formation of sensory-motor reflexes, and impaired learning abilities in the postnatal period.
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37775701
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Fallopian tube lesions as potential precursors of early ovarian cancer: a comprehensive proteomic analysis.
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Ovarian cancer is the leading cause of death from gynecologic cancer worldwide. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype of ovarian cancer. While the origin of ovarian tumors is still debated, it has been suggested that HGSC originates from cells in the fallopian tube epithelium (FTE), specifically the epithelial cells in the region of the tubal-peritoneal junction. Three main lesions, p53 signatures, STILs, and STICs, have been defined based on the immunohistochemistry (IHC) pattern of p53 and Ki67 markers and the architectural alterations of the cells, using the Sectioning and Extensively Examining the Fimbriated End Protocol. In this study, we performed an in-depth proteomic analysis of these pre-neoplastic epithelial lesions guided by mass spectrometry imaging and IHC. We evaluated specific markers related to each preneoplastic lesion. The study identified specific lesion markers, such as CAVIN1, Emilin2, and FBLN5. We also used SpiderMass technology to perform a lipidomic analysis and identified the specific presence of specific lipids signature including dietary Fatty acids precursors in lesions. Our study provides new insights into the molecular mechanisms underlying the progression of ovarian cancer and confirms the fimbria origin of HGSC.
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37592830
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Progression of reactive gliosis and astroglial phenotypic changes following stab wound-induced traumatic brain injury in mice.
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Astrocytes are the main homeostatic cells in the central nervous system (CNS) and they have an essential role in preserving neuronal physiology. After brain injury, astrocytes become reactive, and that involves a profound change in the astroglial gene expression program as well as intense cytoskeleton remodeling that has been classically shown by the up-regulation of glial fibrillary acidic protein (GFAP), a pan-reactive gene over-expressed in reactive astrocytes, independently of the type of injury. Using the stab wound rodent model of penetrating traumatic injury in the cortex, we here studied the reactive astroglial morphology and reactive microgliosis in detail at 1, 3, 7, 14, and 28 days post-injury (dpi). By combining immunohistochemistry, morphometrical parameters, and Sholl analysis, we segmented the astroglial cell population into clusters of reactive astrocytes that were localized in the core, penumbra, and distal regions of the stab wound. Specifically, highly reactive clusters with more complex morphology, increased C3, decreased aquaporin-4 (AQP4), and glutamine synthetase (GS) expression, were enriched at 7 dpi when behavioral alterations, microgliosis, and neuronal alterations in injured mice were most significant. While pro-inflammatory gain of function with peripheral lipopolysaccharide (LPS) administration immediately after a stab wound expanded these highly reactive astroglial clusters, the treatment with the NF-κB inhibitor sulfasalazine reduced the abundance of this highly reactive cluster. Increased neuronal loss and exacerbated reactive microgliosis at 7 dpi were associated with the expansion of the highly reactive astroglial cluster. We conclude that highly reactive astrocytes found in stab wound injury, but expanded in pro-inflammatory conditions, are a population of astrocytes that become engaged in pathological remodeling with a pro-inflammatory gain of function and loss of homeostatic capacity. Controlling this astroglial population may be a tempting strategy to reduce neuronal loss and neuroinflammation in the injured brain.
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37471184
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Automatic Diagnosis of Significant Liver Fibrosis From Ultrasound B-Mode Images Using a Handcrafted-Feature-Assisted Deep Convolutional Neural Network.
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The accurate diagnosis of significant liver fibrosis ( ≥ F2) in patients with chronic liver disease (CLD) is critical, as ≥ F2 is a crucial factor that should be considered in selecting an antiviral therapy for these patients. This article proposes a handcrafted-feature-assisted deep convolutional neural network (HFA-DCNN) that helps radiologists automatically and accurately diagnose significant liver fibrosis from ultrasound (US) brightness (B)-mode images. The HFA-DCNN model has three main branches: one for automatic region of interest (ROI) segmentation in the US images, another for attention deep feature learning from the segmented ROI, and the third for handcrafted feature extraction. The attention deep learning features and handcrafted features are fused in the back end of the model to enable more accurate diagnosis of significant liver fibrosis. The usefulness and effectiveness of the proposed model were validated on a dataset built upon 321 CLD patients with liver fibrosis stages confirmed by pathological evaluations. In a fivefold cross validation (FFCV), the proposed model achieves accuracy, sensitivity, specificity, and area under the receiver-operating-characteristic (ROC) curve (AUC) values of 0.863 (95% confidence interval (CI) 0.820-0.899), 0.879 (95% CI 0.823-0.920), 0.872 (95% CI 0.800-0.925), and 0.925 (95% CI 0.891-0.952), which are significantly better than those obtained by the comparative methods. Given its excellent performance, the proposed HFA-DCNN model can serve as a promising tool for the noninvasive and accurate diagnosis of significant liver fibrosis in CLD patients.
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37471185
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A Dynamic Prediction Model Supporting Individual Life Expectancy Prediction Based on Longitudinal Time-Dependent Covariates.
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In the field of clinical chronic diseases, common prediction results (such as survival rate) and effect size hazard ratio (HR) are relative indicators, resulting in more abstract information. However, clinicians and patients are more interested in simple and intuitive concepts of (survival) time, such as how long a patient may live or how much longer a patient in a treatment group will live. In addition, due to the long follow-up time, resulting in generation of longitudinal time-dependent covariate information, patients are interested in how long they will survive at each follow-up visit. In this study, based on a time scale indicator-restricted mean survival time (RMST)-we proposed a dynamic RMST prediction model by considering longitudinal time-dependent covariates and utilizing joint model techniques. The model can describe the change trajectory of longitudinal time-dependent covariates and predict the average survival times of patients at different time points (such as follow-up visits). Simulation studies through Monte Carlo cross-validation showed that the dynamic RMST prediction model was superior to the static RMST model. In addition, the dynamic RMST prediction model was applied to a primary biliary cirrhosis (PBC) population to dynamically predict the average survival times of the patients, and the average C-index of the internal validation of the model reached 0.81, which was better than that of the static RMST regression. Therefore, the proposed dynamic RMST prediction model has better performance in prediction and can provide a scientific basis for clinicians and patients to make clinical decisions.
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37471186
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Comb Detection for Measuring Shear Wave Propagation.
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Plane wave compounding (PWC) is widely used to measure the propagation of shear waves. Implementing PWC on most commercial ultrasound scanners is challenging because all channel (>128) data must be processed or transferred to the host computing unit in real time. Comb detection transmits multiple focused beams simultaneously and results in a reduced number of receive lines to be processed in parallel. These comb beams are scanned laterally to acquire receive lines at different lateral positions in order to obtain data over a large region of interest (ROI). One of the potential issues with using multiple simultaneously transmitted beams is the issue of crosstalk between the beams. Crosstalk is analyzed through simulated beam patterns, simulated B-mode images, and motion data from shear wave elastography (SWE) experiments. Using a Hamming window on transmit and receive can suppress crosstalk to 1.2% root-mean-square error (RMSE, normalized RMSE to the peak magnitude of the reference signal) for shear wave motion signals. Four comb beams with three laterally scanned locations cover almost the entire field of view (FOV) and achieve the same frame rate as PWC with three angles. Phantom and in vivo studies demonstrate comparable motion data of comb detection to PWC in terms of motion signal quality and measured phase velocity. In addition, comb detection provides motion with lower noise and stronger signals than PWC, which is believed to be due to the advantages of transmitting focused beams rather than plane waves (PWs).
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37471188
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Beyond Supervised Learning for Pervasive Healthcare.
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The integration of machine/deep learning and sensing technologies is transforming healthcare and medical practice. However, inherent limitations in healthcare data, namely scarcity, quality, and heterogeneity, hinder the effectiveness of supervised learning techniques which are mainly based on pure statistical fitting between data and labels. In this paper, we first identify the challenges present in machine learning for pervasive healthcare and we then review the current trends beyond fully supervised learning that are developed to address these three issues. Rooted in the inherent drawbacks of empirical risk minimization that underpins pure fully supervised learning, this survey summarizes seven key lines of learning strategies, to promote the generalization performance for real-world deployment. In addition, we point out several directions that are emerging and promising in this area, to develop data-efficient, scalable, and trustworthy computational models, and to leverage multi-modality and multi-source sensing informatics, for pervasive healthcare.
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37471187
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Network Biomarker Detection from Gene Co-expression Network Using Gaussian Mixture Model Clustering.
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Finding network biomarkers from gene co-expression networks (GCNs) has attracted a lot of research interest. A network biomarker is a topological module, i.e., a group of densely connected nodes in a GCN, in which the gene expression values correlate with sample labels. Compared with biomarkers based on single genes, network biomarkers are not only more robust in separating samples from different categories, but are also able to better interpret the molecular mechanism of the disease. The previous network biomarker detection methods either employ distance based clustering methods or search for cliques in a GCN to detect topological modules. The first strategy assumes that the topological modules should be spherical in shape, and the second strategy requires all nodes to be fully connected. However, the relations between genes are complex, as a result, genes in the same biological process may not be directly, strongly connected. Therefore, the shapes of those modules could be oval or long strips. Hence, the shapes of gene functional modules and gene disease modules may not meet the aforementioned constraints in the previous methods. Thus, previous methods may break up the genes belonging to the same biological process into different topological modules due to those constraints. To address this issue, we propose a novel network biomarker detection method by using Gaussian mixture model clustering which allows more flexibility in the shapes of the topological modules. We have evaluated the performance of our method on a set of eight TCGA cancer datasets. The results show that our method can detect network modules that possess better discriminate power, and provide biological insights.
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37471190
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Location-Aware Encoding for Lesion Detection in 68Ga-DOTATATE Positron Emission Tomography Images.
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OBJECTIVE
Lesion detection with positron emission tomography (PET) imaging is critical for tumor staging, treatment planning, and advancing novel therapies to improve patient outcomes, especially for neuroendocrine tumors (NETs). Current lesion detection methods often require manual cropping of regions/volumes of interest (ROIs/VOIs) a priori, or rely on multi-stage, cascaded models, or use multi-modality imaging to detect lesions in PET images. This leads to significant inefficiency, high variability and/or potential accumulative errors in lesion quantification. To tackle this issue, we propose a novel single-stage lesion detection method using only PET images.
METHODS
We design and incorporate a new, plug-and-play codebook learning module into a U-Net-like neural network and promote lesion location-specific feature learning at multiple scales. We explicitly regularize the codebook learning with direct supervision at the network's multi-level hidden layers and enforce the network to learn multi-scale discriminative features with respect to predicting lesion positions. The network automatically combines the predictions from the codebook learning module and other layers via a learnable fusion layer.
RESULTS
We evaluate the proposed method on a real-world clinical 68Ga-DOTATATE PET image dataset, and our method produces significantly better lesion detection performance than recent state-of-the-art approaches.
CONCLUSION
We present a novel deep learning method for single-stage lesion detection in PET imaging data, with no ROI/VOI cropping in advance, no multi-stage modeling and no multi-modality data.
SIGNIFICANCE
This study provides a new perspective for effective and efficient lesion identification in PET, potentially accelerating novel therapeutic regimen development for NETs and ultimately improving patient outcomes including survival.
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37471189
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Uncertainty-Aware Source-Free Domain Adaptive Semantic Segmentation.
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Source-Free Domain Adaptation (SFDA) is becoming topical to address the challenge of distribution shift between training and deployment data, while also relaxing the requirement of source data availability during target domain adaptation. In this paper, we focus on SFDA for semantic segmentation, in which pseudo labeling based target domain self-training is a common solution. However, pseudo labels generated by the source models are particularly unreliable on the target domain data due to the domain shift issue. Therefore, we propose to use Bayesian Neural Network (BNN) to improve the target self-training by better estimating and exploiting pseudo-label uncertainty. With the uncertainty estimation of BNNs, we introduce two novel self-training based components: Uncertainty-aware Online Teacher-Student Learning (UOTSL) and Uncertainty-aware FeatureMix (UFM). Extensive experiments on two popular benchmarks, GTA 5 → Cityscapes and SYNTHIA → Cityscapes, show the superiority of our proposed method with mIoU gains of 3.6% and 5.7% over the state-of-the-art respectively.
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37471191
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Parameterized Gompertz-Guided Morphological AutoEncoder for Predicting Pulmonary Nodule Growth.
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The growth rate of pulmonary nodules is a critical clue to the cancerous diagnosis. It is essential to monitor their dynamic progressions during pulmonary nodule management. To facilitate the prosperity of research on nodule growth prediction, we organized and published a temporal dataset called NLSTt with consecutive computed tomography (CT) scans. Based on the self-built dataset, we develop a visual learner to predict the growth for the following CT scan qualitatively and further propose a model to predict the growth rate of pulmonary nodules quantitatively, so that better diagnosis can be achieved with the help of our predicted results. To this end, in this work, we propose a parameterized Gempertz-guided morphological autoencoder (GM-AE) to generate any future-time-span high-quality visual appearances of pulmonary nodules from the baseline CT scan. Specifically, we parameterize a popular mathematical model for tumor growth kinetics, Gompertz, to predict future masses and volumes of pulmonary nodules. Then, we exploit the expected growth rate on the mass and volume to guide decoders generating future shape and texture of pulmonary nodules. We introduce two branches in an autoencoder to encourage shape-aware and textural-aware representation learning and integrate the generated shape into the textural-aware branch to simulate the future morphology of pulmonary nodules. We conduct extensive experiments on the self-built NLSTt dataset to demonstrate the superiority of our GM-AE to its competitive counterparts. Experiment results also reveal the learnable Gompertz function enjoys promising descriptive power in accounting for inter-subject variability of the growth rate for pulmonary nodules. Besides, we evaluate our GM-AE model on an in-house dataset to validate its generalizability and practicality. We make its code publicly available along with the published NLSTt dataset.
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37471192
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A Novel Spatial Position Prediction Navigation System Makes Surgery More Accurate.
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During intravascular interventional surgery, the 3D surgical navigation system can provide doctors with 3D spatial information of the vascular lumen, reducing the impact of missing dimension caused by digital subtraction angiography (DSA) guidance and further improving the success rate of surgeries. Nevertheless, this task often comes with the challenge of complex registration problems due to vessel deformation caused by respiratory motion and high requirements for the surgical environment because of the dependence on external electromagnetic sensors. This article proposes a novel 3D spatial predictive positioning navigation (SPPN) technique to predict the real-time tip position of surgical instruments. In the first stage, we propose a trajectory prediction algorithm integrated with instrumental morphological constraints to generate the initial trajectory. Then, a novel hybrid physical model is designed to estimate the trajectory's energy and mechanics. In the second stage, a point cloud clustering algorithm applies multi-information fusion to generate the maximum probability endpoint cloud. Then, an energy-weighted probability density function is introduced using statistical analysis to achieve the prediction of the 3D spatial location of instrument endpoints. Extensive experiments are conducted on 3D-printed human artery and vein models based on a high-precision electromagnetic tracking system. Experimental results demonstrate the outstanding performance of our method, reaching 98.2% of the achievement ratio and less than 3 mm of the average positioning accuracy. This work is the first 3D surgical navigation algorithm that entirely relies on vascular interventional robot sensors, effectively improving the accuracy of interventional surgery and making it more accessible for primary surgeons.
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37745281
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Social, political and legal determinants of kidney health: Perspectives from lower- and middle-income countries with a focus on India.
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The social determinants of health (SDoH) are the non-medical factors that influence kidney health outcomes directly or indirectly in a substantial manner and include conditions in which people are born, grow, work, live, and age. Many such challenges in lower- and middle- income countries have an unfavourable impact on kidney health. These conditions potentially influence economic policies and systems, development agendas, social norms, social policies, and political systems. In addition, many political and legal factors also determine and modify the ultimate outcome in patients with kidney disease. Legal factors that ensure universal health care, promote gender and racial equality, prevent malpractices and regulate strict laws in the field of kidney transplantation are the paramount determinants for the provision of necessary kidney care. Converging lines of evidence have supported the impact of social variables such as socioeconomic resources, social inclusion, housing conditions, educational attainment, and financial status on kidney health, particularly affect vulnerable and disadvantaged groups and result in challenges in kidney care delivery. Furthermore, the climate is an important SDoH that plays a crucial role in the occurrence, prevalence, and progression of kidney diseases as highlighted by the presence of higher prevalence of chronic kidney disease in hot tropical countries. The rising incidence of water and vector-borne diseases causing acute kidney injury is another consequence of disruptive environmental and climate change which is detrimental to kidney health. Political risk factors such as conflict also have a devastating influence on kidney health. The relationship between SDoH and kidney health outcomes requires more clarity. Gaps in the current knowledge need to be identified to inform the development of appropriate interventions to address upstream socio-economic risk factors for kidney disease.
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37410489
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AP Radiographic Assessment of the Pediatric Pelvis for Developmental Dysplasia of the Hip.
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Mastering the art of roentgenographic analysis of the pediatric AP pelvis is paramount in the evaluation of developmental dysplasia of the hip. Understanding the normal radiographic development and the age-dependent changes in normal values allows assessment for pathologic changes. The goal of improving the analysis of the AP pelvis is to increase early detection of disease, assess progress toward normal values, and precisely follow the effects of treatment to improve clinical outcomes.
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37410490
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Prevalence and correlates of androgen dependence: a meta-analysis, meta-regression analysis and qualitative synthesis.
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PURPOSE OF REVIEW
To investigate the prevalence and correlates of androgen dependence among users. A meta-analysis, meta-regression analysis, and qualitative synthesis were conducted based on a systematic literature search in Google Scholar, ISO Web of Science, PsycNET, and PubMed.
RECENT FINDINGS
Twenty-six studies were included in the review and 18 studies ( N = 1782) in the statistical analysis. The overall lifetime androgen dependence prevalence was 34.4% [95% confidence interval (CI): 27.8-41.7, Q = 113.1, I2 = 85.0, P < 0.001]. Although males (36.1%, P < 0.001) and females (37.0%, P = 0.188) did not differ ( Q = 0.0, P = 0.930) in dependence prevalence, controlling for other study characteristics, higher study male sample proportion was related to higher dependence prevalence. Combined interview and questionnaire assessments showed higher prevalence compared to interviews only. Publications from 1990-1999 generated higher prevalence compared to 2000-2009 and 2010-2023 publications. Dependents were associated with a wide array of demographic inequalities, and biophysical, cognitive, emotional, and psychosocial problems.
SUMMARY
One of three persons who initiate androgen use experiences dependence along with various serious disorders. Androgen use and dependence should be considered an important public health issue requiring targeted health interventions.
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37808624
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Comparison of the Oral Health-Related Quality of Life, Sleep Quality, and Oral Health Literacy in Sleep and Awake Bruxism: Results from Family Medicine Practice.
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Objectives
Bruxism is a common oral behaviour. This study aimed to compare oral health-related quality of life, sleep quality, and oral health literacy in patients with and without possible sleep bruxism (SB) and awake bruxism (AB).
Materials and Methods
A cross-sectional study including 249 volunteers was conducted in a family medicine clinic of a tertiary hospital in Istanbul, Turkey. The American Sleep Medicine Association Bruxism Diagnostic Criteria, Pittsburgh Sleep Quality Index (PSQI), Oral Health-Related Quality of Life (OHRQoL) tool, Decay Missing Filled Total Teeth (DMFT) score, and Health Literacy Dental Scale-Short Form (HeLD-14) were assessed by face-to-face interviews. Data were examined using Kruskal-Wallis and Mann-Whitney U tests, Spearman correlation, and logistic regression analysis.
Results
The presence of SB and AB was detected as 41.4% and 21.7%, respectively, among 91 males and 158 females, with a mean age of 36.64 ± 11.60 years. Sleep and awake bruxers had a lower oral health-related quality of life (odds ratio (OR): 0.816, 95% confidence interval (CI) = 0.770-0.864 and OR: 0.923, 95% CI = 0.956-0.982, respectively). Poor sleep quality was detected 1.28 times higher in sleep bruxism (OR: 1.277, 95% CI = 1.152-1.415) and 1.14 times higher in awake bruxism (OR: 1.141, 95% CI = 1.230-1.058). The DMFT score was found to be 1.13 times higher in SB (OR: 1.129, 95% CI = 1.043-1.223). A higher HeLD-14 score was associated with a lower DMFT score (p < 0.001; r = -0.240). The oral health literacy score was lower in AB and SB groups than in patients without bruxism, but it was not statistically significant (p = 0.267, p = 0.376).
Conclusion
A lower oral health-related quality of life and poor sleep quality would be expected in the presence of SB or AB. However, patients may not be aware of it unless asked by a physician regardless of oral health literacy level.
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38081113
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Highly biocidal poly(vinyl alcohol)-hydantoin/starch hybrid gels: A "Trojan Horse" for Bacillus subtilis.
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HYPOTHESIS
Poly (vinyl alcohol) (PVA) cryogels can be functionalized with n-Halamines to confer biocidal features useful for their application as wound-dressing tools. Their efficacy can be boosted by stably embedding a polymeric bacterial food source (e.g., starch) in the gel matrix. The bioavailability of the food source lures bacteria inside the gel network via chemotactic mechanisms, promoting their contact with the biocidal functionalities and their consequent inactivation.
EXPERIMENTS
The synthesis of a novel hydantoin-functionalized PVA (H-PVA-hyd) is proposed. The newly synthesized H-PVA-hyd polymer was introduced in the formulation of H-PVA-based cryogels. To promote the cryogelation of the systems we exploited phase-separation mechanisms employing either a PVA carrying residual acetate groups (L-PVA) or starch as phase-segregating components. The permanence of the biocidal functionality after swelling was investigated via proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FT-IR) microscopy. The activated H-PVA-hyd cryogels have been tested against bacteria with amylolytic activity (Bacillus subtilis) and the outcomes were analyzed by direct observation via confocal laser scanning microscopy (CLSM).
FINDINGS
The cryogels containing starch resulted in being the most effective (up to 90% bacterial killing), despite carrying a lower amount of hydantoin groups than their starch-free counterparts, suggesting that their improved efficacy relies on a "Trojan Horse" type of mechanism.
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37960174
|
Association of Chrononutrition Indices with Anthropometric Parameters, Academic Performance, and Psychoemotional State of Adolescents: A Cross-Sectional Study.
|
Adolescents are an at-risk group for circadian misalignment. The contribution of sleep-wake rhythm instability to the psychoemotional, cognitive, and weight disorders of adolescents has been studied in sufficient detail. At the same time, there is insufficient information about the association between chrononutrition indices and the well-being of adolescents. The aim of this study is to investigate the relationship between chrononutrition indices and academic achievement, psychoemotional state, and anthropometric indicators in adolescents. The study involved 12,759 students in grades 6-11 of secondary schools, aged 14.2 ± 1.7 years old; 57.2% of whom were girls. Participants provided personal data, frequency and time of meals during the day and at night, on weekdays and weekends, and completed the Zung Self-Rating Depression Scale and the Yale Food Addiction Scale. There is a U-shaped association between eating mid-phase (EPFc), eating jetlag (EJL), and eating window (EW) with GPA, ZSDSI, and FA. At the same time, the frequency of night eating (NE) is linearly associated with the studied parameters. NE is the strongest predictor of ZSDSI (β = 0.24), FA (β = 0.04), and GPA (β = -0.22). EPFc, EJL, and EW practically do not differ in the strength of their association with the studied indicators. ZSDSI is most closely associated with the chrononutrition indices. There is a weak negative association between BMI and EW (β = -0.03) and NE (β = -0.04). Thus, circadian eating disorders are more often observed in adolescents with poor academic performance, high levels of depression, and food addiction.
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37960175
|
Prospective Association between Total and Trimester-Specific Gestational Weight Gain Rate and Physical Growth Status in Children within 24 Months after Birth.
|
In this study, our aim was to investigate the potential correlation between the mother's total gestational weight gain (GWG) rate and the trimester-specific GWG rate (GWGR) with the physical development status of the child within 24 months of age. We utilized linear regression models and linear mixed effects models to explore both time point and longitudinal relationships between GWGR and children's anthropometric outcome z-scores at 0, 1, 2, 4, 6, 9, 12, 18, and 24 months. To examine the critical exposure windows, we employed multiple informant models. We also conducted a stratified analysis considering pre-pregnancy BMI and the gender of the children. Our findings revealed notable positive associations between total GWGR and z-scores for body mass index for age (BMIZ), head circumference for age (HCZ), weight for age (WAZ), length for age (LAZ), and weight for length (WHZ) across different trimesters of pregnancy (pint < 0.05). The GWGR during the first two trimesters mainly influenced the relationship between total GWGR and BMIZ, WAZ, and LAZ, while the GWGR during the first trimester had a significant impact on the correlation with HCZ (0.206, 95% CI 0.090 to 0.322). Notably, the associations of GWGR and children's BMIZ were pronounced in male children and pre-pregnancy normal-weight women. In conclusion, our study findings indicated that a higher GWGR during each trimester was associated with greater physical growth during the first 24 months of life, especially GWGR in the first and second trimesters.
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37960176
|
Regional and Age-Related Variations in Blood Calcium Levels among Patients with Plasmodium falciparum and P. vivax malaria: A Systematic Review and Meta-Analysis.
|
Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to synthesize the evidence on the association between blood calcium levels and malaria severity. A systematic literature search was conducted in the Embase, Scopus, PubMed, Ovid, and Google Scholar databases. The studies that investigated calcium levels in participants with malaria were reviewed and included for synthesis. The quality of included studies was assessed based on a standardized checklist by the Joanna Briggs Institute (JBI) critical appraisal checklists. The thematic synthesis had been used for qualitative synthesis. For the quantitative synthesis, the meta-analysis was performed to estimate the pooled effect sizes for differences in calcium levels between groups of participants using a random effect model using Hedge's g as a measure of effect size. Out of the 4574 identified records, 14 studies were reviewed. The thematic synthesis across these studies noted a consistent theme: reduced calcium levels in malaria patients compared to uninfected controls. However, the meta-analysis encompassing three specific analyses-comparing calcium levels between malaria patients and controls, severe and non-severe malaria cases, and fatal cases versus survivors-showed no significant difference in calcium levels. The statistics were as follows: (1) p = 0.15, Hedge's g: -1.00, 95% CI: -2.37-0.38, I2: 98.97, 9 studies; (2) p = 0.35, Hedge's g: -0.33, 95% CI: -1.02-0.36, I2: 81.61, 3 studies; and (3) p = 0.71, Hedge's g: -0.14, 95% CI: -0.91-0.62, I2: 87.05, 3 studies. Subgroup analyses indicated that regional disparities, especially between Africa and Asia, and participant age groups may influence these outcomes. While a trend of decreased calcium levels in malaria patients was observed, the meta-analytical results suggest regional and age-related variations. Further investigations should emphasize these differences to better guide clinical management, prognostic applications, and the crafting of policies concerning malaria's metabolic effects.
|
38050921
|
Turning and Repositioning Frequency to Prevent Hospital-Acquired Pressure Injuries Among Adult Patients: Systematic Review.
|
Turning and repositioning is considered one of the strategies to reduce the incidence of pressure injuries (PIs) among hospitalized patients, as it helps to redistribute and minimize direct pressure on the targeted skin and enhance blood perfusion in the affected areas. The frequency of turning and repositioning is generally uniform across clinical settings, with most clinical guidelines recommending a substantial change in a patient's position according to their health status. Notably, the optimal time interval between the position changes has not yet been established. Therefore, this study aimed to review the current literature in relation to the frequency of turning and repositioning adult patients to prevent PIs. The author used a systematic review following Whittemore and Knafl's review strategy. The author used the following databases: CINAHL, Scopus, PubMed, ProQuest, Ovid, MedLine, Web of Science, and Google Scholar. During the search, Boolean logic operators, MeSH terms, and keywords were utilized. The researcher followed the Johns Hopkins Nursing Evidence-based Practice Grading Scale to evaluate the quality of selected studies. The search yielded 723 articles, of which 10 were included in this review. These 10 articles revealed several frequency intervals for comparison purposes: 2-hourly, 3-hourly, 4-hourly, and 6-hourly depending on the healthcare setting, with a combination of supine, 30° tilt, or 90° tilt. This review shows that the optimal frequency of turning and repositioning to prevent PIs remains unclear and further investigation is necessary. Considering the varying nature of clinical settings, there is a lack of clarity regarding a golden standard for the same. Therefore, patients' health conditions should be considered when choosing the proper frequency to prevent PIs.
|
38081119
|
Does needle size matter? Effects of micro-hypodermic needle injections of botulinum toxin type A in patients with hemifacial spasm.
|
INTRODUCTION
Botulinum toxin type A (BoNT/A) injections are the first-line treatment for primary hemifacial spasms (HFS), but require frequent painful injections. Although micro-hypodermic needles are commonly used for aesthetic BoNT/A injections to lessen pain and bruising, their benefits in HFS remain unclear.
OBJECTIVE
To compare side effects of BoNT/A injection, specifically pain and bruising, between primary HFS patients who received injections using micro-hypodermic needles (34-G) and those using standard needles (30-G).
METHODS
This cross-over, double-blind, randomised controlled trial involved HFS patients who received BoNT/A injections using either a 34-G or 30-G needle at two visits 12 weeks apart. Primary outcomes, pain and bruising were assessed immediately after injection using the Visual Analogue Scale (VAS) and Short-form McGill Pain Questionnaire (Thai version, SF-MPQ). Bruise assessment was also conducted one week after each injection. Secondary outcomes involved comparing efficacy of BoNT/A between the two types of needles and assessing other complications beyond pain and bruising.
RESULTS
65 HFS patients (47 women and 18 men; mean age 59.46 ± 11.48 years; mean disease duration 5.86 ± 4.16 years) were included in the study. Patients who received 34-G needle injections reported significantly reduced pain, as indicated by VAS, total SF-MPQ scores, and bruise scores, compared to those who received 30-G needle injections (p < 0.001, each). There were no differences in efficacy or occurrence of other complications associated with BoNT/A between the two needle types.
CONCLUSION
In HFS patients, BoNT/A injections using micro-hypodermic needles resulted in reduced pain and bruising, compared to standard needles, while maintaining similar BoNT/A benefits.
|
37990550
|
Liquid marbles: review of recent progress in physical properties, formation techniques, and lab-in-a-marble applications in microreactors and biosensors.
|
Liquid marbles (LMs) are nonsticking droplets whose surfaces are covered with low-wettability particles. Owing to their high mobility, shape reconfigurability, and widely accessible liquid/particle possibilities, the research on LMs has flourished since 2001. Their physical properties, fabrication mechanisms, and functionalisation capabilities indicate their potential for various applications. This review summarises the fundamental properties of LMs, the recent advances (mainly works published in 2020-2023) in the concept of LMs, physical properties, formation methods, LM-templated material design, and biochemical applications. Finally, the potential development and variations of LMs are discussed.
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38050927
|
Cuttlefish-Inspired Photo-Responsive Antibacterial Microparticles with Natural Melanin Nanoparticles Spray.
|
Topical antibiotics can be utilized to treat periodontitis, while their delivery stratagems with controlled release and long-lasting bactericidal inhibition are yet challenging. Herein, inspired by the defensive behavior of cuttlefish expelling ink, this work develops innovative thermal-responsive melanin-integrated porous microparticles (MPs) through microfluidic synthesis for periodontitis treatment. These MPs are composed of melanin nanoparticles (NPs), poly(N-isopropylacrylamide) (PNIPAM), and agarose. Benefiting from the excellent biocompatibility and large surface area ratio of MPs, they can deliver abundant melanin NPs. Under near-infrared irradiation, the melanin NPs can convert photo energy into thermal energy. This leads to agarose melting and subsequent shrinkage of the microspheres induced by pNIPAM, thereby facilitating the release of melanin NPs. In addition, the released melanin NPs can serve as a highly effective photothermal agent, displaying potent antibacterial activity against porphyromonas gingivalis and possessing natural anti-inflammatory properties. These unique characteristics are further demonstrated through in vivo experiments, showing the antibacterial effects in the treatment of infected wounds and periodontitis. Therefore, the catfish-inspired photo-responsive antibacterial MPs with controlled-release drug delivery hold tremendous potential in clinical antibacterial applications.
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38050928
|
Medication literacy and its social contextuality.
|
This article aims to contribute to the discussion about medication literacy, by focussing on the social contextuality of the information mobilised in the use of medicines. We aim to explore the social construction processes of medication literacy, as an essential dimension for a more layperson-centred approach in the promotion of literacy in this field. This approach is justified by the growing social and cultural dissemination of medication use, the diversification of its uses beyond health and illness, and the increasing degree of lay autonomy in managing its use. The article is organised in two main sections. In the first section, we review the social history of medication literacy, including a discussion of the social contextuality of literacy phenomena. In the second section, the analysis of social contextuality is operationalised with a focus on information, covering: (i) ways of relating to institutional information and sources of information about medication; (ii) contexts of sociability in which information is shared and validated. This analysis is empirically supported by selected results from two research projects, conducted in Portugal, on the consumption of medicines and dietary supplements for performance purposes - that is, for the management and/or improvement of cognitive, bodily or relational performance.
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38050929
|
Application of N-Terminal Site-Specific Biotin and Digoxigenin Conjugates to Clinical Anti-drug Antibody Assay Development.
|
Biotin- and digoxigenin (DIG)-conjugated therapeutic drugs are critical reagents used for the development of anti-drug antibody (ADA) assays for the assessment of immunogenicity. The current practice of generating biotin and DIG conjugates is to label a therapeutic antibody with biotin or DIG via primary amine groups on lysine or N-terminal residues. This approach modifies lysine residues nonselectively, which can impact the ability of an ADA assay to detect those ADAs that recognize epitopes located at or near the modified lysine residue(s). The impact of the lysine modification is considered greater for therapeutic antibodies that have a limited number of lysine residues, such as the variable heavy domain of heavy chain (VHH) antibodies. In this paper, for the first time, we report the application of site-specifically conjugated biotin- and DIG-VHH reagents to clinical ADA assay development using a model molecule, VHHA. The site-specific conjugation of biotin or DIG to VHHA was achieved by using an optimized reductive alkylation approach, which enabled the majority of VHHA molecules labeled with biotin or DIG at the desirable N-terminus, thereby minimizing modification of the protein after labeling and reducing the possibility of missing detection of ADAs. Head-to-head comparison of biophysical characterization data revealed that the site-specific biotin and DIG conjugates demonstrated overall superior quality to biotin- and DIG-VHHA prepared using the conventional amine coupling method, and the performance of the ADA assay developed using site-specific biotin and DIG conjugates met all acceptance criteria. The approach described here can be applied to the production of other therapeutic-protein- or antibody-based critical reagents that are used to support ligand binding assays.
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38050930
|
Dopant Enhanced Conjugated Polymer Thin Film for Low-Power, Flexible and Wearable DMMP Sensor.
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Conjugated polymer has the potential to be applied on flexible devices as an active layer, but further investigation is still hindered by poor conductivity and mechanical stability. Here, this work demonstrates a dopant-enhanced conductive polymer thin film and its application in dimethyl methylphosphonate (DMMP) sensor. Among five comparable polymers this work employs, poly(bisdodecylthioquaterthiophene) (PQTS12) achieves the highest doping efficiency after doped by FeCl3 , with the conductivity increasing by about five orders of magnitude. The changes in Young's modulus are also considered to optimize the conductivity and flexibility of this thin film, and finally the decay of conductivity is only 9.2% after 3000 times of mechanical bending. This work applies this thin film as the active layer of the DMMP gas sensor, which could be operated under 1 mV driving voltage and 28 nW power consumption, with a sustainable durability against bending and compression. In addition, this sensor is provided with alarm capability while exposed to the DMMP atmospheres at different hazard levels. This work expects that this general approach could offer solutions for the fabrication of low-power and flexible gas sensors, and provide guidance for next-generation wearable devices with broader applications.
|
37410502
|
Go Across Immersive Technology: A Preliminary Study of the Design and Development of a System for Gait Training Using Virtual Reality.
|
Virtual reality (VR) allows visuotactile interaction in a virtual environment. VR has several potential applications such as surgical training, phobia treatments, and gait rehabilitation. However, further interface development is required. Therefore, the objective of this study was to develop a noninvasive wearable device control to a VR gait training program. It consists of custom-made insoles with vibratory actuators, and plantar pressure sensor-based wireless interface with a VR game. System usability testing involved a habituation period and three gaming sessions. Significant gait improvement was associated with game scores (P < 0.05). This VR gait training system allowed real-time virtual immersive interaction with anticipatory stimulus and feedback during gait.
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37259459
|
Computational Chemistry for the Identification of Lead Compounds for Radiotracer Development.
|
The use of computer-aided drug design (CADD) for the identification of lead compounds in radiotracer development is steadily increasing. Traditional CADD methods, such as structure-based and ligand-based virtual screening and optimization, have been successfully utilized in many drug discovery programs and are highlighted throughout this review. First, we discuss the use of virtual screening for hit identification at the beginning of drug discovery programs. This is followed by an analysis of how the hits derived from virtual screening can be filtered and culled to highly probable candidates to test in in vitro assays. We then illustrate how CADD can be used to optimize the potency of experimentally validated hit compounds from virtual screening for use in positron emission tomography (PET). Finally, we conclude with a survey of the newest techniques in CADD employing machine learning (ML).
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37410511
|
Prenatal Substance Use Among Young Pregnant Sexual Minority People.
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Sexual minority (SM) youth have higher rates of substance use and pregnancy but are absent from the prenatal substance use literature. We modeled the impact of SM identity and syndemic factors on prenatal substance use among 14- to 21-year-olds. Pregnant people completed an online survey (n = 357). Prenatal substance use was regressed on SM identity, controlling for other syndemic factors (e.g., depressive symptoms, intimate partner violence) and household substance use. Pregnant SM participants (n = 125) were primarily bisexual and were more likely to use tobacco and illicit drugs than heterosexual participants (n = 232). The association between SM identity and prenatal tobacco use was not attenuated by syndemic factors, prenatal cannabis use, or household tobacco use. SM people need increased support for smoking cessation to redress health inequities in tobacco use, prevent prenatal exposures to tobacco, and limit the long-term consequences of tobacco use on health.
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37838938
|
A Hematopoietic Stem Cell Transplant Recipient with Nephrotic Syndrome and Immune Complex Deposits in Tubular Basement Membrane: A Rare Case Report.
|
Following allogenic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) may develop which may affect several organs. Although the presence of nephrotic syndrome after HSCT is rare, sometimes it occurs in the setting of GVHD. The most common histological finding on kidney biopsy of patients with proteinuria owing to GVHD is membranous glomerulonephritis (MGN). However, reports of immune complex deposition in the tubular basement membrane (TBM) and glomerular basement membrane (GBM) are extremely rare. Herein we present a 65-year-old female with a history of HSCT at six years ago who was referred to Dr.Shariati Hospital in Tehran with nephrotic syndrome. Secondary serologic laboratory tests were all normal. The histopathologic study indicated diffuse GBM and TBM thickening, spike formation, infiltration of inflammatory mononuclear cells in tubulointerstitial area and acute tubular injury in light microscopy. Immunofluorescence staining showed immune complex deposits in GBM, mesangial cells, and TBM. DOI: 10.52547/ijkd.7550.
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37838940
|
Treatment adherence to olfactory training: a real-world observational study.
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BACKGROUND
Olfactory training (OT) is considered an effective intervention for most causes of smell loss and is recommended as a long-term treatment. However, the treatment adherence of OT remains unclear. This study aims to identify the frequency and causalities for lack of adherence to OT.
METHODS
In this prospective study, 53 patients previously diagnosed with olfactory dysfunction (OD), who were recommended to perform OT, were enrolled. Patients underwent olfactory testing using Sniffin' Sticks for threshold, discrimination, and identification (TDI) and a subjective numeric rating scale (NRS) at a baseline and follow-up visit. In addition, patients answered a six-item treatment adherence questionnaire. The primary outcome measures were clinically relevant improvements according to the TDI (≥5.5) and NRS (≥1) scores.
RESULTS
Out of 53 patients, 45 performed OT. Among patients who performed OT, 31% discontinued the use of OT on their own due to a self-perceived improvement, while 51% discontinued use due to lack of improvements in olfaction. In these patients, the average duration of OT use was five months. After controlling for baseline duration of OD, baseline TDI score and smell loss aetiologies, discontinuing OT due to a lack of self-perceived improvement remained significantly associated with worse TDI and NRS outcomes at follow-up.
CONCLUSIONS
Our data show that therapeutical adherence to OT is low, regardless of patients' perception of olfactory function. Olfactory improvement leads to decreased training due to satisfaction, while lack of improvement leads to non-adherence based on disappointing subjective outcome. Patients should be advised to perform OT consistently.
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37838939
|
Effects of sound energy on proteins and their complexes.
|
Mechanical energy in the form of ultrasound and protein complexes intuitively have been considered as two distinct unrelated topics. However, in the past few years, increasingly more attention has been paid to the ability of ultrasound to induce chemical modifications on protein molecules that further change protein-protein interaction and protein self-assembling behavior. Despite efforts to decipher the exact structure and the behavior-modifying effects of ultrasound on proteins, our current understanding of these aspects remains limited. The limitation arises from the complexity of both phenomena. Ultrasound produces multiple chemical, mechanical, and thermal effects in aqueous media. Proteins are dynamic molecules with diverse complexation mechanisms. This review provides an exhaustive analysis of the progress made in better understanding the role of ultrasound in protein complexation. It describes in detail how ultrasound affects an aqueous environment and the impact of each effect separately and when combined with the protein structure and fold, the protein-protein interaction, and finally the protein self-assembly. It specifically focuses on modifying role of ultrasound in amyloid self-assembly, where the latter is associated with multiple neurodegenerative disorders.
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37990569
|
The Study and Relevance of Pulp Chamber Anatomy in Endodontics - A Comprehensive Review.
|
With the ever-increasing understanding of tooth anatomy, there is a renewed focus on the pulp chamber as an important component of the root canal system. For example, the pulp chamber is of critical relevance during diagnostic procedures such as pulp sensibility tests, deep caries removal, vital pulp treatments, access cavity preparation, tooth whitening, tooth restoration as well as methods for examining the floor of the pulp chamber to aid the detection of root canal orifices or the presence of perforations and cracks. The more recent concept of minimal invasive endodontics has also created a need to understand better the anatomy of the pulp chamber. The purpose of this article is to discuss the research methods used to study pulp chamber anatomy and the significance of the pulp chamber in endodontic research and clinical practice. In addition, directions for future research are emphasised.
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37990567
|
Small increases in ambient temperature reduce offspring body mass in an equatorial mammal.
|
Human-induced climate change is leading to temperature rises, along with increases in the frequency and intensity of heatwaves. Many animals respond to high temperatures through behavioural thermoregulation, for example by resting in the shade, but this may impose opportunity costs by reducing foraging time (therefore energy supply), and so may be most effective when food is abundant. However, the heat dissipation limit (HDL) theory proposes that even when energy supply is plentiful, high temperatures can still have negative effects. This is because dissipating excess heat becomes harder, which limits processes that generate heat such as lactation. We tested predictions from HDL on a wild, equatorial population of banded mongooses (Mungos mungo). In support of the HDL theory, higher ambient temperatures led to lighter pups, and increasing food availability made little difference to pup weight under hotter conditions. This suggests that direct physiological constraints rather than opportunity costs of behavioural thermoregulation explain the negative impact of high temperatures on pup growth. Our results indicate that climate change may be particularly important for equatorial species, which often experience high temperatures year-round so cannot time reproduction to coincide with cooler conditions.
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37259466
|
Mucosal Genes Expression in Inflammatory Bowel Disease Patients: New Insights.
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Individual differences in IBD illness severity, behavior, progression, and therapy response are evident. Since a break in the intestinal epithelial barrier causes IBD to begin, mucosal gene expression in IBD is crucial. Due to its high sensitivity and dynamic nature, molecular analysis of biomarkers in intestinal biopsies is feasible and provides a reliable means of evaluating localized inflammation. The goal of this investigation was to discover alterations in gene expression in the inflamed mucosa of IBD patients undergoing treatment with 5-amino salicylic acid (5ASA) (N = 39) or anti-TNF drugs (N = 22). The mucosal expression of numerous IBD-related genes was evaluated using qPCR. We discovered that the levels of the proteins Lipocalin-2 (LCN2), Nitric Oxide Synthase 2 (NOS2), Mucin 2 (MUC2), Mucin 5AC (MUC5AC), and Trefoil factor 1 (TFF1), which are overexpressed in untreated IBD patients compared to non-IBD subjects, are decreased by both therapy regimens. On the other hand, anti-TNF medicine helped the levels of ABCB1 and E-cadherin return to normal in IBD patients who were not receiving treatment.
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37592872
|
SARS-CoV-2 Hybrid Immunity: The Best of Both Worlds.
|
Three and a half years into the coronavirus disease 2019 (COVID-19) pandemic, the nature and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still remains unclear. Current COVID-19 mRNA vaccines have been shown to provide minimal protection against infection with XBB variants but substantial protection against severe disease. However, such protection appears to wane quickly. In contrast, protection from the combination of both vaccination and infection, termed "hybrid immunity", has been shown to be greater in magnitude and durability than that provided by either vaccine immunity or natural immunity alone.
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38050943
|
Insight into Dendrites Issue in All Solid-State Batteries with Inorganic Electrolyte: Mechanism, Detection and Suppression Strategies.
|
All solid-state batteries (ASSBs) are regarded as one of the promising next-generation energy storage devices due to their expected high energy density and capacity. However, failures due to unrestricted growth of lithium dendrites (LDs) have been a critical problem. Moreover, the understanding of dendrite growth inside solid-state electrolytes is limited. Since the dendrite process is a multi-physical field coupled process, including electrical, chemical, and mechanical factors, no definitive conclusion can summarize the root cause of LDs growth in ASSBs till now. Herein, the existing works on mechanism, identification, and solution strategies of LD in ASSBs with inorganic electrolyte are reviewed in detail. The primary triggers are thought to originate mainly at the interface and within the electrolyte, involving mechanical imperfections, inhomogeneous ion transport, inhomogeneous electronic structure, and poor interfacial contact. Finally, some of the representative works and present an outlook are comprehensively summarized, providing a basis and guidance for further research to realize efficient ASSBs for practical applications.
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37592879
|
A 1% colloidal oatmeal OTC cream is clinically effective for the management of mild to moderate atopic dermatitis in Black or African American children.
|
BACKGROUND
The efficacy and safety of an over-the-counter (OTC) 1% colloidal oatmeal cream versus a ceramide-based prescription barrier cream in children with mild-to-moderate atopic dermatitis (AD) were previously described.
OBJECTIVES
Here, findings are reported for the Black/African American subgroup.
METHODS
Patients were randomized to 1% oatmeal cream or prescription barrier cream twice daily or as needed for three weeks. Assessments included Eczema Area and Severity Index (EASI) scores, Investigator's Global Atopic Dermatitis Assessment (IGADA) scores, and patients'/caregivers' assessment of eczema signs and symptoms.
RESULTS
Overall, 49 Black/African American children aged 2-15 years with mild/moderate AD were included. At week 3, mean (SD) changes from baseline in EASI scores were -2.4 (1.7) with 1% oatmeal cream and -2.1 (2.3) with barrier cream; improvements were observed from week 1. At week 3, mean (SD) changes from baseline in IGADA scores were -0.6 (0.7) and -0.7 (0.6), respectively. Improvements in subjective ratings of signs/symptoms of eczema were observed. Both study treatments were well tolerated.
CONCLUSION
OTC 1% oatmeal cream was at least as effective and safe as prescription barrier cream in this population, providing a novel, fast-acting, and cost-effective option for the symptomatic treatment of mild-to-moderate AD in Black/African American children.
|
38081136
|
A comparative analysis of mathematical methods for detecting lactate thresholds using muscle oxygenation data during a graded cycling test.
|
Threshold determination for improving training and sports performance is important for researchers and trainers, who currently use different methods for determining lactate, ventilatory or muscle oxygenation (SmO2) thresholds. Our study aimed to compare the identification of the intensity at the first and second thresholds using lactate and SmO2 data by different mathematical methods in different muscles during a graded cycling test. Twenty-six cyclists (15 males and 11 females; 23 ±6 years, 1.71 ±0.09 m, 64.3 8.8 Kg and 12 3 training hours per week) performed a graded test on the cycle ergometer. Power output and saturation of muscle oxygen in four muscles (vastus lateralis, biceps femoris, gastrocnemius and tibialis anterior) were measured, along with systemic lactate concentration. Our results showed that any method was reliable for determining the first muscle oxygenation threshold (MOT1) when comparing the lactate threshold in any muscle. However, the best method for determining the second muscle oxygenation threshold (MOT2) was the Exp-Dmax (p < 0.01; ICC=0.79-0.91) in all muscles. In particular, the vastus lateralis muscle showed the highest intraclass correlation coefficient (ICC=0.91, CI95%[0.81, 0.96]). However, results varied per sex across all muscles analyzed. In conclusion, although the first muscle oxygenation threshold could not be determined using mathematical methods in all the muscles analyzed, the Exp-Dmax method presented excellent results in detecting the second systemic threshold in the vastus lateralis.
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38081137
|
Full-Spectrum Responsive Naphthalimide/Perylene Diimide with a Giant Internal Electric Field for Photocatalytic Overall Water Splitting.
|
The co-assembly naphthalimide/perylene diimide (NDINH/PDINH) supramolecular photocatalysts were successfully synthesized via a rapid solution dispersion method. A giant internal electric field (IEF) in co-assembly structure was built by the larger local dipole. NDINH coated on PDINH could reduce the reflected electric field over PDINH to improve its responsive activity to ultraviolet light. Resultantly, an efficient full-spectrum photocatalytic overall water splitting activity with H2 and O2 evolution rate of 317.2 and 154.8 μmol g-1 h-1 for NDINH/PDINH together with optimized O2 evolution rate with 2.61 mmol g-1 h-1 using AgNO3 as a sacrificial reagent were achieved. Meanwhile, its solar-to-hydrogen efficiency was enhanced to 0.13%. The enhanced photocatalytic activity was primarily attributed to the IEF between NDINH and PDINH, significantly accelerating transfer and separation of photogenerated carriers. Additionally, a direct Z-scheme pathway of carriers contributed to a high redox potential. The strategy provided a new perspective for the design of supramolecular photocatalysts.
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37471220
|
ARGLRR: A Sparse Low-Rank Representation Single-Cell RNA-Sequencing Data Clustering Method Combined with a New Graph Regularization.
|
The development of single-cell transcriptome sequencing technologies has opened new ways to study biological phenomena at the cellular level. A key application of such technologies involves the employment of single-cell RNA sequencing (scRNA-seq) data to identify distinct cell types through clustering, which in turn provides evidence for revealing heterogeneity. Despite the promise of this approach, the inherent characteristics of scRNA-seq data, such as higher noise levels and lower coverage, pose major challenges to existing clustering methods and compromise their accuracy. In this study, we propose a method called Adjusted Random walk Graph regularization Sparse Low-Rank Representation (ARGLRR), a practical sparse subspace clustering method, to identify cell types. The fundamental low-rank representation (LRR) model is concerned with the global structure of data. To address the limited ability of the LRR method to capture local structure, we introduced adjusted random walk graph regularization in its framework. ARGLRR allows for the capture of both local and global structures in scRNA-seq data. Additionally, the imposition of similarity constraints into the LRR framework further improves the ability of the proposed model to estimate cell-to-cell similarity and capture global structural relationships between cells. ARGLRR surpasses other advanced comparison approaches on nine known scRNA-seq data sets judging by the results. In the normalized mutual information and Adjusted Rand Index metrics on the scRNA-seq data sets clustering experiments, ARGLRR outperforms the best-performing comparative method by 6.99% and 5.85%, respectively. In addition, we visualize the result using Uniform Manifold Approximation and Projection. Visualization results show that the usage of ARGLRR enhances the separation of different cell types within the similarity matrix.
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37471222
|
Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury.
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Liver sinusoidal endothelial cells (LSECs) rapidly clear lipopolysaccharide (LPS) from the bloodstream and establish intimate contact with immune cells. However, their role in regulating liver inflammation remains poorly understood. We show that LSECs modify their chemokine expression profile driven by LPS or interferon-γ (IFN-γ), resulting in the production of the myeloid- or lymphoid-attracting chemokines CCL2 and CXCL10, respectively, which accumulate in the serum of LPS-challenged animals. Natural killer (NK) cell exposure to LSECs in vitro primes NK cells for higher production of IFN-γ in response to interleukin-12 (IL-12) and IL-18. In livers of LPS-injected mice, NK cells are the major producers of this cytokine. In turn, LSECs require exposure to IFN-γ for CXCL10 expression, and endothelial-specific Cxcl10 gene deletion curtails NK cell accumulation in the inflamed livers. Thus, LSECs respond to both LPS and immune-derived signals and fuel a positive feedback loop of immune cell attraction and activation in the inflamed liver tissue.
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37471223
|
Lung injury induces a polarized immune response by self-antigen-specific CD4+ Foxp3+ regulatory T cells.
|
Self-antigen-specific T cells are prevalent in the mature adaptive immune system but are regulated through multiple mechanisms of tolerance. However, inflammatory conditions such as tissue injury may allow these T cells to break tolerance and trigger autoimmunity. To understand how the T cell repertoire responds to the presentation of self-antigen under highly stimulatory conditions, we use peptide:major histocompatibility complex (MHC) class II tetramers to track the behavior of endogenous CD4+ T cells with specificity to a lung-expressed self-antigen in mouse models of immune-mediated lung injury. Acute injury results in the exclusive expansion of CD4+ regulatory T cells (Tregs) that is dependent on self-antigen recognition and interleukin-2 (IL-2). Conversely, conventional CD4+ T cells of the same self-antigen specificity remain unresponsive even following Treg ablation. Thus, the self-antigen-specific CD4+ T cell repertoire is poised to serve a regulatory function during acute tissue damage to limit further damage and the possibility of autoimmunity.
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37775762
|
High triglyceride-glucose (TyG) index is associated with poor prognosis of heart failure with preserved ejection fraction.
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BACKGROUND
The impact of insulin resistance on the prognosis of heart failure with preserved ejection fraction (HFpEF) remains unknown. This study aimed to investigate the association between the triglyceride-glucose (TyG) index, an easily calculated marker of insulin resistance, and the long-term prognosis of HFpEF.
METHODS
A total of 823 patients with HFpEF were enrolled in the study. The TyG index was determined using the formula ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The primary endpoint was all-cause death. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization. Restricted cubic spline, multivariate Cox proportional hazard models, and competing risk models were used for analyses.
RESULTS
During a median follow-up period of 3.16 years, 147 (17.8%) all-cause deaths, 139 (16.8%) CV deaths, and 222 (27.0%) HF rehospitalizations occurred. Restricted cubic spline analysis revealed a J-shaped association between the TyG index and the mortality and rehospitalization rates. In the multivariate Cox proportional hazard models, compared with those in the lowest TyG index tertile, patients in the highest tertile exhibited the greatest susceptibility to all-cause death (HR 1.53, 95% CI 1.19-1.98) and CV death (HR 1.52, 95% CI 1.19-1.96). In the competing risk model, a significant association between the TyG index and HF rehospitalization was observed (HR 1.31, 95% CI, 1.07-1.61).
CONCLUSION
A high TyG index is associated with an increased risk of mortality and rehospitalization in patients with HFpEF. The TyG index may serve as a promising prognostic marker for patients with HFpEF.
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37471224
|
Poly(GR) interacts with key stress granule factors promoting its assembly into cytoplasmic inclusions.
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C9orf72 repeat expansions are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly(GR) proteins are toxic to neurons by forming cytoplasmic inclusions that sequester RNA-binding proteins including stress granule (SG) proteins. However, little is known of the factors governing poly(GR) inclusion formation. Here, we show that poly(GR) infiltrates a finely tuned network of protein-RNA interactions underpinning SG formation. It interacts with G3BP1, the key driver of SG assembly and a protein we found is critical for poly(GR) inclusion formation. Moreover, we discovered that N6-methyladenosine (m6A)-modified mRNAs and m6A-binding YTHDF proteins not only co-localize with poly(GR) inclusions in brains of c9FTD/ALS mouse models and patients with c9FTD, they promote poly(GR) inclusion formation via the incorporation of RNA into the inclusions. Our findings thus suggest that interrupting interactions between poly(GR) and G3BP1 or YTHDF1 proteins or decreasing poly(GR) altogether represent promising therapeutic strategies to combat c9FTD/ALS pathogenesis.
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37775765
|
Assessing sugar intake rapidly - a short form of the Marburg Sugar Index (MSI).
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BACKGROUND
Sugar intake is a major nutritional factor in the development of dental caries. To further clarify its contribution to oral health-related diseases, population-based investigations are recommended. To facilitate economic and reliable assessment of sugar intake, a short form of the approved Marburg Sugar Index (MSI) was developed.
METHODS
According to the principles of item reduction based on original data, a six-item-short form was constructed. A total of 468 participants (aged 15-81) answered the short form together with the long form in a counterbalanced cross-over design, and with two questionnaires concerning self-efficacy and decisional balance in oral health to verify construct validity.
RESULTS
Comparable item characteristics to the original MSI and a high correlation with the long form prove the usefulness of the short form, which was processed by the participants in less than one minute. Low correlations to the other two constructs show discriminant validity.
CONCLUSION
The new short form of the MSI (MSI-S) can replace the long form, especially in population-based studies with no restrictions on assessment quality but with sufficient time saved to add other variables necessary to explore oral health-related issues.
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37775764
|
Effects of allyl isothiocyanate fumigation on medicinal plant root knot disease control, plant survival, and the soil bacterial community.
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BACKGROUND
Allyl isothiocyanate (AITC) is a natural product with high volatility that is used as a biofumigant to alleviate soil-borne plant diseases, and problems such as root knot nematodes (RKNs) that necessitate continuous cropping. However, little research has assessed the effects of AITC fumigation on medicinal plants.
RESULTS
AITC significantly reduced the population of RKNs in soil (p < 0.0001) and showed an excellent RKN disease control effect within 6 months after sowing Panax notoginseng (p < 0.0001). The seedling survival rate of 2-year-old P. notoginseng was approximately 1.7-fold higher after soil treatment with AITC (p = 0.1008). 16S rRNA sequencing indicated that the AITC treatment affected bacterial richness rather than diversity in consecutively cultivated (CC) soil. Furthermore, biomarkers with statistical differences between AITC-treated and untreated CC soil showed that Pirellulales (order), Pirellulaceae (family), Pseudomonadaceae (family), and Pseudomonas (genus) played important roles in the AITC-treated group. In addition, the microbiome functional phenotypes predicted using the BugBase tool suggested that AITC treatment is more conducive to improving CC soil through changes in the bacterial community structure. Crucially, our research also suggested that AITC soil treatment significantly increases soil organic matter (p = 0.0055), total nitrogen (p = 0.0054), and available potassium (p = 0.0373), which promotes the survival of a succeeding medicinal plant (Polygonatum kingianum).
CONCLUSION
AITC is an ecologically friendly soil treatment that affects the top 10 bacterial richness but not diversity. It could also provide a basis for a useful agricultural soil management measure to alleviate soil sickness.
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37775767
|
The neutrophil-lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003-2016.
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BACKGROUND
Evidence regarding the neutrophil-lymphocyte ratio (NLR) and mortality risk in diabetes patients is scarce. This study investigated the relationship of the NLR with all-cause and cardiovascular mortality risk in diabetes patients.
METHODS
Diabetes patients (n = 3251) from seven National Health and Nutrition Examination Survey (NHANES) cycles (2003-2016) were included in this study. The cause of death and mortality status of the participants were obtained from National Death Index records. Restricted cubic spline (RCS) was used to visualize the association of the NLR with mortality risk. The maximally selected rank statistics method (MSRSM) was used to determine the optimal NLR cutoff value corresponding to the most significant association with survival outcomes. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NLR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NLR in predicting survival outcomes.
RESULTS
During a median follow-up of 91 months (interquartile range, 55-131 months), 896 (27.5%) of the 3251 diabetes patients died, including 261 (8.0%) with cardiovascular deaths and 635 (19.5%) with noncardiovascular deaths. The RCS regression analysis showed a positive linear association between the NLR and all-cause and cardiovascular mortality (both p > 0.05 for nonlinearity) in diabetes patients. Participants were divided into higher (> 3.48) and lower (≤ 3.48) NLR groups according to the MSRSM. In the multivariable-adjusted model, compared with participants with a lower NLR, those with a higher NLR had a significantly higher risk of both all-cause (HR 2.03, 95% confidence interval (CI) 1.64-2.51, p < 0.0001) and cardiovascular mortality (HR 2.76, 95% CI 1.84-4.14, p < 0.0001). The association was consistent in subgroup analyses based on age, sex, smoking status, drinking status, and hypertension, with no significant interaction between the aforementioned characteristics and the NLR (p interaction > 0.05). The time-dependent ROC curve showed that the areas under the curve of the 1-, 3-, 5-, and 10-year survival rates were 0.72, 0.66, 0.64, and 0.64 for all-cause mortality and 0.69, 0.71, 0.69 and 0.65, respectively, for cardiovascular mortality.
CONCLUSION
An elevated NLR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.
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37808665
|
Short- and long-term experience-dependent neuroplasticity interact during the perceptual learning of concurrent speech.
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Plasticity from auditory experiences shapes brain encoding and perception of sound. However, whether such long-term plasticity alters the trajectory of short-term plasticity during speech processing has yet to be investigated. Here, we explored the neural mechanisms and interplay between short- and long-term neuroplasticity for rapid auditory perceptual learning of concurrent speech sounds in young, normal-hearing musicians and nonmusicians. Participants learned to identify double-vowel mixtures during ∼45 minute training sessions recorded simultaneously with high-density EEG. We analyzed frequency-following responses (FFRs) and event-related potentials (ERPs) to investigate neural correlates of learning at subcortical and cortical levels, respectively. While both groups showed rapid perceptual learning, musicians showed faster behavioral decisions than nonmusicians overall. Learning-related changes were not apparent in brainstem FFRs. However, plasticity was highly evident in cortex, where ERPs revealed unique hemispheric asymmetries between groups suggestive of different neural strategies (musicians: right hemisphere bias; nonmusicians: left hemisphere). Source reconstruction and the early (150-200 ms) time course of these effects localized learning-induced cortical plasticity to auditory-sensory brain areas. Our findings confirm domain-general benefits for musicianship but reveal successful speech sound learning is driven by a critical interplay between long- and short-term mechanisms of auditory plasticity that first emerge at a cortical level.
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37592915
|
Exposing high-activity (111) facet CoO octahedral loading MXene quantum dots for efficient and stable photocatalytic H2 evolution.
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Photocatalytic splitting of water for hydrogen generation is a green and renewable solution for converting solar energy to chemical energy; thus, the development of high-performance and stable photocatalytic materials has emerged as a research hotspot recently. Herein, a heterostructure composite photocatalyst of octahedral CoO uniformly modified with novel nitrogen-doped MXene quantum dots (N-MQDs) is successfully designed using a typical solvothermal approach. The optimum photocatalytic hydrogen evolution efficiency of the prepared N-MQDs@CoO heterojunction composite is 82.54 μmol g-1 h-1 with visible light, which is 16.57 times higher compared to the pure CoO. A series of photoelectrochemical tests were further performed to elucidate the photocatalytic hydrogen evolution mechanism. The remarkable improvement of activity is primarily attributed to the synergistic interaction between the closely spaced interface contacts and energy level matching among high conductivity Ti3C2 MXene quantum dots with CoO octahedra, dramatically hastening the segregation and transfer of photo-generated carriers. This study provides new ideas for the construction of MXene quantum dot-based co-photocatalysts with highly efficient photocatalytic performance and stability toward solar energy conversion applications.
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37960247
|
Sex-Specific Effects of a Maternal Obesogenic Diet High in Fat and Sugar on Offspring Adiposity, Growth, and Behavior.
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With rising rates of human obesity, this study aimed to determine the relationship between maternal diet-induced obesity, offspring morphometrics, and behavior in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of the HFHS offspring was reduced for the first postnatal week but not thereafter, with HFHS female offspring having higher body weights by weaning due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. The maternal diet did not affect the offspring's locomotor activity or social behavior in either sex. Both the male and female HFHS offspring displayed reduced anxiety-related behaviors, with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in the male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behavior of male and female offspring, with sex-specific differences.
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37440911
|
Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.
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As a ligand-dependent transcription factor, retinoid-associated orphan receptor γt (RORγt) that controls T helper (Th) 17 cell differentiation and interleukin (IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions. An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production. Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric- or allosteric-binding sites in the ligand-binding domain. Some of small-molecule inhibitors have entered clinical evaluations. Therefore, in current review, the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted. Notably, the recently developed RORγt inhibitors were summarized, with an emphasis on their optimization from lead compounds, efficacy, toxicity, mechanisms of action, and clinical trials. The limitations of current development in this area were also discussed to facilitate future research.
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37808676
|
Structural basis of Cfr-mediated antimicrobial resistance and mechanisms for its evasion.
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The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally conserved adenine residue 2503 (A2503) of the 23S rRNA by the methyltransferase Cfr. Despite its clinical significance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. In this work, we developed a method to express a functionally-active Cfr-methyltransferase in the thermophilic bacterium Thermus thermophilus and report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-tRNAs. Our structures reveal that an allosteric rearrangement of nucleotide A2062 upon Cfr-methylation of A2503 is likely responsible for the inability of some PTC inhibitors to bind to the ribosome, providing additional insights into the Cfr resistance mechanism. Lastly, by determining the structures of the Cfr-methylated ribosome in complex with the antibiotics iboxamycin and tylosin, we provide the structural bases behind two distinct mechanisms of evading Cfr-mediated resistance.
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37929999
|
Differences in resilience profiles between military veterans and the general population: An exploratory latent profile analysis using the HUNT-4 survey.
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Using latent profile analyses, the current work investigated levels of adverse childhood experiences, symptoms of anxiety and depression and 3 dimensions of relational promotive factors) to identify resilience profiles in a large general population sample (N = 161,622, mean age = 53.02; SD = 17.80; 56.1% females). We then used the same method to identify the resilience profiles of military veterans (N = 386, mean age = 43.47; SD = 10.08; 9.8% females), all of whom had served in Afghanistan. A four-profile-solution was the best fitting for the general population (High resilient 30%, Moderate resilient 13%, Low resilient 53%, Work/social-based resilience 4%), while a three-profile-solution had the best fit in the veteran cohort (Family-based resilience 28%, Work/social-based resilience 62%, Hardy loners 10%). To ground the identified profiles in occupational function, we also checked how they predicted reports of sleep difficulties, job demand and job control. Despite both samples inhabiting a geographic region known for high socioeconomic similarity among residents, we found marked differences in profile-solutions between the military veterans and the general population. Our findings suggests that resilience profiles are highly influenced by cohort characteristics and the specific resources needed to manage a given stressor load. Accordingly, the generalisability of specific protective factors may be low across distinct cohorts, and reliable findings need to be obtained in specific populations as defined by stressor context, sample characteristics, and relevant outcomes.
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37930001
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Choledococele as a cause of recurrent abdominal pain and biliary sepsis.
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We report the case of a 91-year-old female with acute cholangitis and long-standing symptoms of recurrent colic- related abdominal pain after cholecystectomy. She was diagnosed by abdominal CT of saccular dilation of the intramural bile duct in the duodenum suggesting choledococele. ERCP was performed in which the presumptive diagnosis was confirmed, and choledochotomy and choledochoplasty were done with excellent subsequent progress. Choledococele is the least common type of biliary cyst. It consists of a cystic dilation of the intramural portion of the common bile duct that protrudes into the duodenal lumen and causes symptoms of recurrent abdominal pain and biliary events. ERCP is a key test in both diagnosis and treatment except when they cannot be approached by this technique or malignancy is suspected.
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37745328
|
Lupus IgA1 autoantibodies synergize with IgG to enhance pDC responses to RNA-containing immune complexes.
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Autoantibodies to nuclear antigens are hallmarks of the autoimmune disease systemic lupus erythematosus (SLE) where they contribute to pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes of autoantibodies contribute to disease, including the production of the critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) in response to immune complexes (ICs). We focused on IgA, which is the second most prevalent isotype in serum, and along with IgG is deposited in glomeruli in lupus nephritis. Here, we show that individuals with SLE have IgA autoantibodies against most nuclear antigens, correlating with IgG against the same antigen. We investigated whether IgA autoantibodies against a major SLE autoantigen, Smith ribonucleoproteins (Sm/RNPs), play a role in IC activation of pDCs. We found that pDCs express the IgA-specific Fc receptor, FcαR, and there was a striking ability of IgA1 autoantibodies to synergize with IgG in RNA-containing ICs to generate robust pDC IFNα responses. pDC responses to these ICs required both FcαR and FcγRIIa, showing a potent synergy between these Fc receptors. Sm/RNP IC binding to and internalization by pDCs were greater when ICs contained both IgA1 and IgG. In addition, binding of Sm/RNP ICs generated with IgA1-sufficient serum correlated to pDC FcαR expression, but not FcγRIIa expression. Lastly, pDCs from individuals with SLE had higher binding of IgA1-containing ICs and higher expression of FcαR than pDCs from healthy control individuals. Taken together, our data show a new mechanism by which IgA1 anti-nuclear antibodies contribute to SLE pathogenesis.
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37899813
|
Prediction of Prognosis Acute Pancreatitis with Inflammatory Markers and Patient Characteristics Compared to the Scoring System: Real-Life Data.
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Objectives
Acute pancreatitis (AP) is an inflammatory disease with a high morbidity and mortality rate. It is one of the most common causes of hospitalization among gastrointestinal system diseases. Inflammatory and other factors that predict the severity of AP are very important for patient management. This study will analyze the factors associated with the severity of AP.
Methods
The sample consisted of 514 patients. Demographic characteristics, comorbid diseases, causes of AP, body mass index (BMI), tobacco use, blood at admission, amylase, lipase, leukocyte, neutrophil, lymphocyte, C-reactive protein (CRP), mean platelet volume, red cell distribution width, albumin, calcium, and CRP values at 48th h were recorded. The bedside index of severity in AP (BISAP), Ranson score, neutrophil-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) values was calculated and recorded. The relationship between these parameters and the severity of AP was analyzed according to the Atlanta classification.
Results
Participants had a mean age of 55±17.8 years. More than half the participants were women (n=272, 52.9%). Biliary causes were the most common etiological causes (n=299, 58.2%). Most participants had mild pancreatitis (n=416, 80.9%). The severity of AP was associated with tobacco use, high BMI, thrombocytosis, high NLR, high PLR, high 48th h CRP, hypoalbuminemia, hypocalcemia, aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT ratio), and high Ranson and BISAP scores.
Conclusion
Biochemical markers that give rapid results in the early period can provide information about the severity of AP. We may develop new scores by combining these parameters.
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37592928
|
Cork-Derived Carbon Sheets for High-Performance Na-Ion Capacitors.
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S-doped carbon sheets have been easily prepared by deconstructing the 3D cellular structure of a fully sustainable and renewable biomass material such as cork through a mild ball-milling process. S-doping of the material (>14 wt % S) has been achieved by using sulfur as an earth-abundant, cost-effective, and environmentally benign S-dopant. Such synthesized materials provide large Na storage capacities in the range of 300-550 mAh g-1 at 0.1 A g-1 and can handle large current densities of 10 A g-1, providing 55-140 mAh g-1. Their increased packing density compared to the 3D pristine structure allows them to also provide good volumetric capacities in the range of 285-522 mAh cm-3 at 0.1 A g-1 and 53-133 mAh cm-3 at 10 A g-1. In addition, highly porous carbon sheets (SBET > 2700 m2 g-1) have been produced from the same carbon precursor by rationally designing the chemical activation approach. These materials are able to provide good anion storage capacities/capacitances of up to 100-114 mAh g-1/163-196 F g-1. A sodium-ion capacitor assembled with the optimized S-doped carbon sheets and the highly porous carbon sheets with mass matching ratios provided the best energy/power characteristics (90 Wh kg-1 at 29 kW kg-1) in combination with robust cycling stability over 10,000 cycles, with a capacity fade of only 0.0018% per cycle.
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37745348
|
Reviving immunogenic cell death upon targeting TACC3 enhances T-DM1 response in HER2-positive breast cancer.
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Immunogenic cell death (ICD), an immune-priming form of cell death, has been shown to be induced by several different anti-cancer therapies. Despite being the first and one of the most successful antibody-drug conjugates (ADCs) approved for refractory HER2-positive breast cancer, little is known if response and resistance to trastuzumab emtansine (T-DM1) involves ICD modulation that can be leveraged to enhance T-DM1 response. Here, we report that T-DM1 induces spindle assembly checkpoint (SAC)-dependent ICD in sensitive cells by inducing eIF2α phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which are lost in resistance. Accordingly, an ICD-related gene signature correlates with clinical response to T-DM1-containing therapy. We found that transforming acidic coiled-coil containing 3 (TACC3) is overexpressed in T-DM1 resistant cells, and that T-DM1 responsive patients have reduced TACC3 protein while the non-responders exhibited increased TACC3 expression during T-DM1 treatment. Notably, genetic or pharmacological inhibition of TACC3 revives T-DM1-induced SAC activation and induction of ICD markers in vitro. Finally, TACC3 inhibition elicits ICD in vivo shown by vaccination assay, and it potentiates T-DM1 by inducing dendritic cell (DC) maturation and enhancing infiltration of cytotoxic T cells in the human HER2-overexpressing MMTV.f.huHER2#5 (Fo5) transgenic model. Together, our results show that ICD is a key mechanism of action of T-DM1 which is lost in resistance, and that targeting TACC3 restores T-DM1-mediated ICD and overcomes resistance.
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37899817
|
Candidal Infections in the Neonatal Intensive Care Unit: A Retrospective Observational Study.
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Objectives
The aims of this study were to evaluate the demographic characteristics, risk factors, mortality rates, and laboratory findings of infants with fungal sepsis in the Neonatal Intensive Care Unit (NICU).
Methods
This retrospective multicenter study included patients in NICU with Candida spp isolated in blood cultures between November 01, 2019, and September 01, 2022. The patients were evaluated in two groups as Group 1 infants with Candida albicans and Group 2 infants with Candida non-albicans positive blood cultures.
Results
Candida infection was detected in blood cultures in 57 of 3450 patients admitted to the NICU. A total of 57 infants included in the study. Candida infection was determined 1.6% of infants in the study population, and 57% of them were extremely pre-term infants. There was no significant difference between the two groups in terms of laboratory data. Normal vaginal birth was determined at a higher rate in Group 1. In Group 2, length of hospital stay, duration of total parenteral nutrition (TPN), and mechanical ventilation (MV) were determined to be longer. The mortality due to Candida fungemia was determined as 35%, and of these patients, 65% had an additional medical condition.
Conclusion
In accordance with the literature, this study showed that prolonged MV and longer TPN increased the incidence of fungal sepsis. Therefore, to decrease the fungal sepsis rate of NICU, shortening the hospital stay and effective screening programs are recommended.
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37592931
|
Comparison of a digital iodine-specific dietary screener with 24-hour recall and urinary iodine concentration.
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Mild-to-moderate iodine deficiency remains a problem worldwide, including in Norway. Of particular, concern is fertile, pregnant and lactating women. The Norwegian Dairy Council developed a digital iodine-specific dietary screener (I-screener) for the assessment of iodine intake levels but has yet to be validated. The aim was thus to investigate the relative validity of the I-screener by comparing estimates of iodine intake from the I-screener against a single 24-hour recall (24HR) and urinary iodine concentration (UIC) in fertile women. Healthy females were recruited in Bergen in August-December 2021. Six spot-urine samples from six consecutive days were collected into a pooled sample to assess UIC. Each participant completed a single administration of the I-screener and the 24HR. The estimated daily iodine intake from the I-screener was compared with the estimations from the 24HR and UIC. Seventy-two women aged 19-39 completed the study. The median UIC was 76 μg/l. Compared with the 24HR, the I-screener placed 83 % of the participants in the same/adjacent tertial, with a slight agreement between the methods (Cohen's kappa = 0⋅187). The present study shows an acceptable correlation between the I-screener and the 24HR (r = 0⋅318), but not between the I-screener and UIC (r = 0⋅122). Despite its varying iodine estimate abilities, the I-screener may be used as an initial screening tool to rank fertile women on an individual level into deficient inadequate, and sufficient iodine intake. However, due to the relatively high risk of misclassification, further assessment of iodine status should follow.
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37838984
|
A systematic review and meta-analysis of the relationship between obsessive-compulsive symptoms and symptoms of proposed orthorexia nervosa: The contribution of assessments.
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OBJECTIVE
This systematic review and meta-analysis aimed to update the literature on orthorexia nervosa (ON), a proposed diagnosis of pathologically 'healthy' eating, by critically analysing the current evidence for the relationship between ON and obsessive-compulsive (OC) symptoms. Further, this paper aimed to compare the ON/OC relationship significance and strength based on when the ON measurement tool was developed.
METHOD
PsycINFO, PubMed and Web of Science databases were queried for quantitative, peer-reviewed studies recruiting adult participants, published in English up to April 2023. Studies not directly comparing ON and OC symptoms were excluded. After full-text review and quality assessment, 40 studies were included in the systematic review and 31 studies in the meta-analysis.
RESULTS
ON assessments created prior to the 2016 revised ON diagnostic criteria do not appear to fully capture OC symptoms. Studies using earlier developed ON assessments demonstrated inconsistent ON/OC relationships whereas studies implementing more recent assessments (from 2018 onwards) found consistently significant, larger relationships, highlighting a previously underrated OC component of ON.
CONCLUSIONS
Early ON studies, and studies utilising early ON assessments should be interpreted with caution, particularly in relation to OC symptom involvement in ON. Future research should validate novel ON assessments and investigate common underlying factors.
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37899823
|
Nutrient synergy: definition, evidence, and future directions.
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Nutrient synergy refers to the concept that the combined effects of two or more nutrients working together have a greater physiological impact on the body than when each nutrient is consumed individually. While nutrition science traditionally focuses on isolating single nutrients to study their effects, it is recognized that nutrients interact in complex ways, and their combined consumption can lead to additive effects. Additionally, the Dietary Reference Intakes (DRIs) provide guidelines to prevent nutrient deficiencies and excessive intake but are not designed to assess the potential synergistic effects of consuming nutrients together. Even the term synergy is often applied in different manners depending on the scientific discipline. Considering these issues, the aim of this narrative review is to investigate the potential health benefits of consuming different nutrients and nutrient supplements in combination, a concept we define as nutrient synergy, which has gained considerable attention for its impact on overall well-being. We will examine how nutrient synergy affects major bodily systems, influencing systemic health. Additionally, we will address the challenges associated with promoting and conducting research on this topic, while proposing potential solutions to enhance the quality and quantity of scientific literature on nutrient synergy.
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37990648
|
New Dipterocarpol-Based Molecules with α-Glucosidase Inhibitory and Hypoglycemic Activity.
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Dammarane triterpenoids are affordable and bioactive natural metabolites with great structural potential, which makes them attractive sources for drug development. The aim of the study was to investigate the potency of new dipterocarpol derivatives for the treatment of diabetes. Two dammaranes (dipterocarpol and its 20(24)-diene derivative) were modified by a Claisen-Schmidt aldol condensation to afford C2(E)-arylidenes in good yields. The majority of the synthesized compounds exhibited an excellent-to-moderate inhibitory effect toward α-glucosidase (from S. saccharomyces), among them eight compounds showed IC50 values less than 10 μM. 3-Oxo-dammarane-2(E)-benzylidenes (holding p-hydroxy- 3 l and p-carbonyl- 3 m substituents) demonstrated the most potent α-glucosidase inhibition with IC50 0.753 and 0.204 μM, being 232- and 857-times more active than acarbose (IC50 174.90 μM), and a high level of NO inhibition in Raw 264.7 cells with IC50 of 1.75 and 4.57 μM, respectively. An in vivo testing of compound 3 m (in a dose of 20 mg/kg) on a model of streptozotocin-induced T1DM in rats showed a pronounced hypoglycemic activity, the ability to reduce effectively the processes of lipid peroxidation in liver tissue and decrease the excretion of glucose and pyruvic acid in the urine. Compound 3 m reduced the death of diabetic rats and preserved their motor activity.
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37990649
|
Influence of vasopressin receptor antagonists on triple-whammy acute kidney injury: A VigiBase analysis.
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Although diuretics play an important role in triple-whammy acute kidney injury (AKI), it is unclear whether the type of diuretic influences the risk of triple-whammy AKI. The aim of this study was to evaluate whether vasopressin receptor antagonists affect triple-whammy AKI. This cross-sectional study used disproportionality analysis of VigiBase data to assess the risk of AKI with various diuretics. Although multiple logistic regression analysis showed that aldosterone antagonists (odds ratio [OR] 2.19, 95% CI 2.01-2.37), loop diuretics (OR 4.40, 95% CI 4.07-4.76) and thiazide diuretics (OR 1.98, 95% CI 1.83-2.15) increased the risk of AKI in patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and renin-angiotensin system inhibitors (RASi), vasopressin receptor antagonists did not increase the risk of AKI in those patients. Vasopressin receptor antagonists might not influence the development of triple-whammy AKI.
|
37440934
|
Diagnostic Accuracy of Cord Bilirubin to Predict the Need for Phototherapy in Healthy Neonates >35-Week Gestational Age: A Systematic Review and Meta-Analysis.
|
Objective
Early discharge puts neonates at risk of delayed detection of jaundice and resulting neurological injury. In these neonates, we can use cord bilirubin to make predictions. In this meta-analysis, we assessed the diagnostic accuracy of cord bilirubin in predicting the need for phototherapy (AAP-2004 or NICE-2010 charts).
Methods
We searched the databases of PubMed, Embase, Cochrane Library, Google Scholar, and Index Medicus for Southeast Asian Region. We included all observational studies that assessed the diagnostic accuracy of cord bilirubin. A bivariate model was used to pool the data in prespecified range of cord bilirubin levels (<1.5 mg/dl, 1.5-2.0 mg/dl, 2.0-2.5 mg/dl, 2.5-3.0 mg/dl, and >3.0 mg/dl). Data were pooled separately for studies including all neonates (no risk stratification), high-risk neonates (Rh and/or ABO incompatibility only), and low-risk neonates (excluded Rh and ABO incompatibility).
Results
Of the 1990 unique records, we studied 153 full texts and included 54 studies in the meta-analysis. For all the three groups of studies, the highest diagnostic odds ratio was noted for a cord bilirubin cut-off of 2.5-3.0 mg/dl (all neonates: 22.5, 95% CI: 21.1, 22.9; high-risk neonates: 75.5, 95% CI: 63, 85.7; low-risk neonates: 91.9; 95% CI: 64, 134.14). Using the same cut-off, the studies including all neonates without risk stratification had a pooled sensitivity of 0.31 (95% CI: 0.18, 0.47) and a pooled specificity of 0.98 (0.96, 0.99) in predicting the need for phototherapy. In studies on high-risk neonates, the pooled sensitivity was 0.8 (0.39, 0.96) and pooled specificity was 0.95 (0.78, 0.99). In studies on low-risk neonates, the pooled sensitivity was 0.74 (0.39, 0.93) and pooled specificity of 0.97 (0.91, 0.99). We noted significant heterogeneity and a high risk of bias in the index test's conduct.
Conclusion
A cord bilirubin cut-off of 2.5-3 mg/dl has good diagnostic accuracy in predicting the need for phototherapy in neonates.
Registration number
CRD42020196216.
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37960279
|
Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease.
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Antrodia cinnamomea (AC), a medicinal mushroom, has multiple beneficial actions, such as acting as a prebiotic. The incidence of chronic kidney disease (CKD) in children has steadily increased year by year, and CKD is related to gut microbiota dysbiosis. Herein, we investigated the renoprotection of solid-state cultivated AC in adenine-induced CKD juvenile rats. CKD was induced in 3-week-old male rats by feeding with adenine (0.5%) for three weeks. Treated groups received oral administration of AC extracts at either a low (10 mg/kg/day) or high dose (100 mg/kg/day) for six weeks. At nine weeks of age, the rats were sacrificed. Renal outcomes, blood pressure, and gut microbiome composition were examined. Our results revealed that AC treatment, either low- or high-dose, improved kidney function, proteinuria, and hypertension in CKD rats. Low-dose AC treatment increased plasma concentrations of short-chain fatty acids (SCFAs). Additionally, we observed that AC acts like a prebiotic by enriching beneficial bacteria in the gut, such as Akkermansia and Turicibacter. Moreover, the beneficial action of AC against CKD-related hypertension might also be linked to the inhibition of the renin-angiotensin system. This study brings new insights into the potential application of AC as a prebiotic dietary supplement in the prevention and treatment of pediatric CKD.
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37960278
|
The Role of Human Milk Oligosaccharides in Myelination, Socio-Emotional and Language Development: Observational Data from Breast-Fed Infants in the United States of America.
|
Infancy is a critical period for neurodevelopment, which includes myelination, synaptogenesis, synaptic pruning, and the development of motor, social-emotional, and cognitive functions. Human milk provides essential nutrients to the infant's developing brain, especially during the first postnatal months. Human milk oligosaccharides (HMOs) are a major component of human milk, and there is growing evidence of the association of individual HMOs with cognitive development in early life. However, to our knowledge, no study has explained these associations with a mechanism of action. Here, we investigated possible mediating associations between HMOs in human milk, brain myelination (measured via myelin water fraction), and measures of motor, language (collected via the Bayley Scales of Infant and Toddler Development (Bayley-III)), and socioemotional development (collected via the Ages and Stages Questionnaire: Social-Emotional Version (ASQ-SE)) in healthy term-born breast-fed infants. The results revealed an association between 6'Sialyllactose and social skills that was mediated by myelination. Furthermore, associations of fucosylated HMOs with language outcomes were observed that were not mediated by myelination. These observations indicate the roles of specific HMOs in neurodevelopment and associated functional outcomes, such as social-emotional function and language development.
|
37960280
|
Effects of Healthy Lifestyles on Chronic Diseases: Diet, Sleep and Exercise.
|
Among the many factors affecting general health and resilience to disease, lifestyle is at the same time the most controllable and the most influential factor [...].
|
37960281
|
Association between Gut Microbiota and Breast Cancer: Diet as a Potential Modulating Factor.
|
Breast cancer (BCa) has many well-known risk factors, including age, genetics, lifestyle, and diet; however, the influence of the gut microbiome on BCa remains an emerging area of investigation. This study explores the connection between the gut microbiome, dietary habits, and BCa risk. We enrolled newly diagnosed BCa patients and age-matched cancer-free controls in a case-control study. Comprehensive patient data was collected, including dietary habits assessed through the National Cancer Institute Diet History Questionnaire (DHQ). 16S rRNA amplicon sequencing was used to analyze gut microbiome composition and assess alpha and beta diversity. Microbiome analysis revealed differences in the gut microbiome composition between cases and controls, with reduced microbial diversity in BCa patients. The abundance of three specific microbial genera-Acidaminococus, Tyzzerella, and Hungatella-was enriched in the fecal samples taken from BCa patients. These genera were associated with distinct dietary patterns, revealing significant associations between the presence of these genera in the microbiome and specific HEI2015 components, such as vegetables and dairy for Hungatella, and whole fruits for Acidaminococus. Demographic characteristics were well-balanced between groups, with a significantly higher body mass index and lower physical activity observed in cases, underscoring the role of weight management in BCa risk. Associations between significant microbial genera identified from BCa cases and dietary intakes were identified, which highlights the potential of the gut microbiome as a source of biomarkers for BCa risk assessment. This study calls attention to the complex interplay between the gut microbiome, lifestyle factors including diet, and BCa risk.
|
37960282
|
Ketogenic Diet Has Moderate Effects on the Fecal Microbiota of Wild-Type Mice.
|
The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has been reported to have neuroprotective effects. The health effects of KD might be linked to an altered gut microbiome, which plays a major role in host health, leading to neuroprotective effects via the gut-brain axis. However, results from different studies, most often based on the 16S rRNA gene and metagenome sequencing, have been inconsistent. In this study, we assessed the effect of a 4-week KD compared to a western diet (WD) on the colonic microbiome of female C57Bl/6J mice by analyzing fecal samples using fluorescence in situ hybridization. Our results showed distinct changes in the total number of gut bacteria following the 4-week KD, in addition to changes in the composition of the microbiome. KD-fed mice showed higher absolute numbers of Actinobacteria (especially Bifidobacteria spp.) and lower absolute levels of Proteobacteria, often linked to gut inflammation, in comparison with WD-fed mice. Furthermore, an increased abundance of the typically rare genus Atopobium was observed. These changes may indicate the possible anti-inflammatory effects of the KD. However, since the overall changes in the microbiota seem low, the KD effects might be linked to the differential abundance of only a few key genera in mice.
|
37899840
|
Rise and shine for eating right: the link between healthy nutrition and chronotype among young adults.
|
Aim
Many studies have examined the relationship between chronotype and general health. Because healthy eating is the basis of health aim of this study is to evaluate the relationship between healthy nutrition attitudes and chronotype in young adults. Methods: This cross-sectional study was conducted with 1,400 young adults (936 females and 464 males). Chronotype was assessed by the Turkish version of the Morningness-Eveningness Questionnaire (MEQ) and the Attitude Scale for Healthy Nutrition (ASHN) was applied by face-to-face interview. Furthermore, 24-h dietary recall was collected. The scores of nutrient adequacy ratio (NAR) and mean adequacy ratio (MAR) were calculated. The anthropometric measurements including body weight and height were taken.
Results
The chronotype distribution of participants according to the MEQ score and MAR score were not significantly different between females and males (p > 0.05). The percentage of participants with high healthy eating attitude was lowest in the evening chronotype and highest in the morning chronotype (49.7, 37.7 and 25.4% in morning-, intermediate-, evening-types, respectively; p = 0.000 for all groups according to the reciprocal comparisons). There was a positive correlation of the MEQ scores with the scores of ASHN (r = 0.282, p < 0.01). ASHN score was shown to be a predictor for MEQ score (β = 0.280, p = 0.000). Moreover, the score of "poor eating habits" was shown to be highest in the evening chronotype and lowest in the morning chronotype (14.9 ± 3.0 and 13.1 ± 3.0, respectively; p < 0.01).
Conclusion
The results of this study indicate that individuals with the evening chronotype are more deficient in terms of healthy nutrition attitudes. Further studies with larger populations will potentially guide the development of health promotion strategies to prevent and treat chronic diseases based on an individual's chronotype.
|
37899841
|
Effects of six different microbial strains on polyphenol profiles, antioxidant activity, and bioaccessibility of blueberry pomace with solid-state fermentation.
|
To explore the effect of different microbial strains on blueberry pomace with solid-state fermentation (SSF), three fungi strains and three lactic acid bacteria (LAB) strains were utilized to investigate with respect to polyphenol profiles, antioxidant capacities, and bioaccessibility. Different strains exhibited different capacities for metabolizing polyphenolic compounds in blueberry pomace. The contents of 10 phenolic acids and 6 flavonoids (except (+)-catechin) were increased in blueberry pomace fermented by Lactobacillus acidophilus (LA). A similar tendency was observed in blueberry pomace fermented by Aspergillus niger (AN) and Lactobacillus plantarum (LP), where the concentration of 8 phenolic acids and 5 flavonoids was enhanced, with the following exceptions: (+)-catechin, ferulic acid, vanillic acid, and quercitrin. Chlorogenic acid and quercetin were the maximum phenolic acids and flavonoids in blueberry pomace with SSF, upgraded at 22.96 and 20.16%, respectively. Contrary to the growth of phenolic acids and flavonoid compounds, all individual anthocyanins showed a decreased trend. Only in the blueberry pomace fermented by AN, all anthocyanidins exhibit a rising trend. After SSF, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenylpicrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) radical scavenging abilities were increased by up to 33.56, 59.89, and 87.82%, respectively. Moreover, the simulated gastrointestinal digestion system revealed that SSF improved the bioaccessibility of polyphenolic compounds. Compared with other strains, LA, LP, and AN showed better excellent capacities for metabolizing polyphenolic compounds, which led to a greater increase in antioxidant activity and bioaccessibility in fermented blueberry pomace.
|
37899842
|
Transformation of arsenic species from seafood consumption during in vitro digestion.
|
Arsenic (As) species analysis is important for the risk evaluation of seafood. Until now, there has been limited information on the change of As species during digestion. Here, the As species in different types of seafood before and after in vitro digestion were investigated. Although inorganic As was not detected in digested fish samples, As(V) contents in digested crabs and scallops were 17.12 ± 1.76 and 138.69 ± 7.53, respectively, which were approximately 2-3 times greater than those of the pre-digestion samples. In further experiments, arsenocholine, dimethylarsinate, arsenobetaine, and monomethylarsonate were all convertible to As(V) during in vitro digestions with different rates. The transformation demonstrates a complex process and could be affected by many factors, such as pH, time, and digestion juice composition, of which pH seemed to be particularly important. Free radicals were responsible for the oxidation in the transformation reactions. Unlike arsenobetaine, arsenocholine seemed to be able to directly transform to monomethylarsonate without the intermediate dimethylarsinate. This study reveals and validates the potential of other species (oAs or/and unknown species) to convert to iAs, identifies the main factors affecting this process, and proposes a reaction pathway. There is an important implication for promoting a more accurate risk assessment of arsenic in foodstuffs.
|
37471279
|
Number of segments with motion abnormalities is better correlated with infarct size in acute myocardial infarction.
|
BACKGROUND
The relationship between the number of segments with motion abnormalities (SMA) on the bull's-eye plots of speckle-tracking echocardiography (STE) and myocardial infarct size (MIS) on late gadolinium-enhanced cardiac MRI (LGE-cMRI) has not been well characterized. This study aimed to determine MIS using the number of SMA in patients with acute myocardial infarction (MI).
METHODS
Left ventricular two-dimensional STE and LGE-cMRI were performed in 380 patients with ST-segment elevation MI within 48 h and 5-6 days after primary percutaneous intervention, respectively.
RESULTS
Patients with impaired global and regional myocardial strain, work and greater number of SMA had significantly larger infarcts ( P < 0.05). Multivariate logistic regression analysis that included myocardial strain, work, and number of SMA showed that total number of SMA [odds ratio (OR) = 1.976; 95% confidence interval (CI): 1.539-2.538, P < 0.0001], the number of segments with paradoxalic systolic movements (SPSM, OR = 3.703; 95% CI: 2.112-6.493, P < 0.0001) were independent risk factors of large MIS (>19%). The area under receiver operating characteristic curve (AUC) of 0.904 (0.866~0.942) for total number of SMA was superior to that for global longitudinal strain (GLS, AUC = 0.813, 0.761~0.865), global work efficiency (GWE, AUC = 0.794, 0.730~0.857) and number of SPSM (AUC = 0.851, 0.804-0.899) to predict a large MIS ( P < 0.05). The optimal cutoff value of total number of SMA was 7, with a sensitivity of 85.31%, a specificity of 81.48%, and an accuracy of 83.27%.
CONCLUSION
Total number of SMA is better associated with infarct size, which provided an incremental prognostic value above established prognostic parameters such as GLS and GWE.
|
37839002
|
[Impact of Cadmium on the expressions of piRNAs in the rat testis].
|
OBJECTIVE
To study the impact of cadmium (Cd) on the expressions of PIWI-interacting RNAs (piRNA) in the rat testis and its possible action mechanism.
METHODS
Twelve 6-week-old SD rats were randomly divided into a Cd-exposure and a control group, the former gavaged with CdCl2 at 3 mg/kg/d and the latter with normal saline, all for 28 successive days. Then the testicular tissues were collected from the rats, sperm concentration and motility were obtained by computer-assisted sperm analysis (CASA), and piRNA sequencing was performed using the gene chip, followed by bioinformatics analysis of differentially expressed piRNAs.
RESULTS
Compared with the controls, the rats in the Cd-exposure group showed significantly decreased sperm concentration and motility (P < 0.05). The expressions of 272 piRNAs were up-regulated and 402 down-regulated after 28 days of Cd exposure, and 4 of the up-regulated piRNAs were consistent with the results of gene chip verification. Bioinformatics analysis showed that the 4 up-regulated piRNA target genes were involved in 50 biological processes, such as negative regulation of apoptosis, positive regulation of gene expression and positive regulation of GTPase activity, and mainly concentrated in 13 signaling pathways including transcription dysregulation, calcium and mitogen-activated protein kinase signaling pathways in cancer. Among them, PIRNA-DQ765261 had a binding site with Bcl-2.
CONCLUSION
Cadmium can induce changes in the expressions piRNAs in the rat testicular tissue, and some piRNAs may be involved in the autophagy and apoptosis of sperm. Bcl-2 may be the target of PIRNA-DQ765261.
|
37839001
|
[Cistanches tubulosa water extract protects the testis against cyclophosphamide-induced injury: Effect and mechanism].
|
OBJECTIVE
To investigate the protective effect of Cistanche tubulosa water extract (CTWE) against cyclophosphamide (CTX)-induced testis injury (TI) in mice and its action mechanism.
METHODS
Thirty male mice were equally randomized into a normal control, a CTX-induced TI model control and a CTWE treatment group. After 7 days of adaptive feeding, the mice in the CTWE treatment group were treated intragastrically with CTWE at 10 g/kg/d, those in the normal control and TI model control groups with the same volume of normal saline qd all for 35 successive days, and those in the TI model control and CTWE treatment groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg/d at 7, 14, 21, 28 and 35 days. Then all the animals were weighed, blood samples collected, and their testes and epididymides harvested for detection of the serum T content, examination of semen quality, measurement of testis weight, observation of histopathological changes in the testis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the mRNA expressions of the genes related to the nuclear factor erythroid-2-related factor (Nrf2) signaling pathway.
RESULTS
The mice in the TI model control group, compared with the normal controls, showed significant decreases in the body weight (［34.13 ± 1.56］ vs ［47.08 ± 1.98］ g, P < 0.05), testis weight (［81.82 ± 10.61］ vs ［148.50 ± 14.82］ mg, P < 0.05), sperm concentration (［32.60 ± 5.29］ vs ［78.90 ± 7.95］ ×10⁶/ml, P < 0.05), sperm motility (［45.20 ± 7.09］% vs ［86.70 ± 5.64］%, P < 0.05), serum T content (［7.49 ± 1.03］ vs ［15.93 ± 1.36］ ng/L, P < 0.05), and SOD level (［152.22 ± 10.66］ vs ［356.10 ± 30.95］ U/mg prot, P < 0.05), but remarkable increases in the percentage of morphologically abnormal sperm (MAS) (［39.30 ± 7.36］% vs ［14.40 ± 3.53］ %, P < 0.05) and MDA level (［54.91 ± 5.12］ vs ［31.71 ± 3.57］ nmol/mg prot, P < 0.05). The animals treated with CTWE, in comparison with the TI model controls, exhibited markedly increased body weight (［40.67 ± 2.13］ vs ［34.13 ± 1.56］ g, P<0.05), testis weight (［121.21 ± 17.38］ vs ［81.82 ± 10.61］ mg, P<0.05), sperm concentration (［58.40 ± 9.94］ vs ［32.60 ± 5.29］ ×10⁶/ml, P < 0.05), sperm motility (［72.30 ± 7.51］ % vs ［45.20 ± 7.09］ %, P < 0.05), serum T content (［10.89 ± 1.07］ vs ［7.49 ± 1.03］ ng/L, P < 0.05) and SOD level (［217.69 ± 24.59］ vs ［152.22 ± 10.66］ U/mg prot, P < 0.05), but decreased percentage of MAS (［22.20 ± 6.07］% vs ［39.30 ± 7.36］%, P < 0.05) and MDA level (［36.41 ± 4.27］ vs ［54.91 ± 5.12］ nmol/mg prot, P < 0.05). The mRNA expressions of Nrf2, HO-1 and NQO-1 in the testis tissue were significantly down-regulated in the TI model controls compared with those in the normal controls (P < 0.05), and remarkably up-regulated in the CTWE treatment group in comparison with those in the TI model group (P < 0.05), while that of Caspase3 markedly increased in the TI model controls (P< 0.05) and decreased in the CTWE treatment group (P < 0.05). Histopathologically, the testis tissue of the TI model controls showed indistinct outlines from the base of the seminiferous tubule to the lumen surface, with disarranged and reduced layers of spermatogenic cells and decreased number of sperm in the seminiferous tubules, while the structure of the spermatogenic tubules recovered almost to normal in the CTWE treatment group.
CONCLUSION
Cistanches tubulosa water extract can effectively inhibit cyclophosphamide-induced testis injury by enhancing the activity of antioxidant enzyme and regulating the expressions of the Nrf2 signaling pathway-related genes.
|
37839004
|
[Lycopene for the treatment of chronic prostatitis / chronic pelvic pain syndrome: Effect and mechanism based on network pharmacology and molecular docking].
|
OBJECTIVE
To explore the action mechanisms of lycopene in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) based on network pharmacology and molecular docking.
METHODS
We obtained the drug targets of lycopene from the databases TCMSP and PharmMapper, the therapeutic targets of CP/CPPS from OMIM, Disgenet and Genecards, and the common targets of lycopene and CP/CPPS with the Venny software. We constructed a protein-protein interaction (PPI) network of lycopene acting on CP/CPPS using the STRING database, screened the core targets with the Cytoscape software, followed by GO functional analysis and KEGG pathway analysis with the R software and molecular docking of lycopene and the core targets using AutoDock Tools, Vina and Pymol.
RESULTS
A total of 187 drug targets, 1 557 disease targets and 46 common targets were screened out. PPI network analysis showed that ALB, IGF1, EGFR, SRC, CASP3 and ESR1 were the core targets of lycopene in the treatment of CP/CPPS. GO functional analysis showed the common targets to be involved in the reproductive structure development, extrinsic apoptotic signaling pathway, and response to reactive oxygen species. KEGG pathway analysis indicated the association of Ras, PI3K-Akt, Rap1, FoxO and MAPK signaling pathways with the mechanism of lycopene acting on CP/CPPS. Molecular docking exhibited a great affinity of lycopene to all the core targets.
CONCLUSION
This study revealed the potential targets and signaling pathways of lycopene in the treatment of CP/CPPS and its action mechanisms from the perspective of network pharmacology and molecular docking, which has provided some reference for future studies.
|
38051012
|
Effects of konjac glucomannan as a freeze-denaturation inhibitor or binder on the physiochemical properties of heat-induced gel of freeze-dried duck blood.
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During freeze-drying, the degradation or eutectic melting of duck blood proteins can reduce the quality of duck blood gels. However, the interaction between proteins and polysaccharides during drying can improve protein-based gel quality. Therefore, here, we investigated the physicochemical properties of heat-induced gels of freeze-dried duck blood (FDB) and FDB with different proportions of the polysaccharide konjac glucomannan (KG), which serves as a freeze-denaturation inhibitor agent (FDA) or binder (BG). The pH and water-holding capacity (WHC) of FDB + KG gels were higher than those of FDB gel without KG (control). Especially, the WHC increased from 11.00% for control to 55.65% for FDB gel with 1% KG as a BG. Consequently, cooking loss and texture parameters of FDB + KG gels decreased. The hardness of control was 2.14 kg, which significantly reduced to 0.12-0.87 kg with KG addition. The highest carbonyl content was observed in control gel, and the thiobarbituric acid reactive substance content was reduced by the addition of 1% KG as an FDA (T1) or 0.8% KG as an FDA with 0.2% KG as a BG (T2) (p < 0.05). These changes might be induced by the alteration of tertiary structure and thermodynamic stability of gels. In conclusion, 1% KG can be used as an FDA to improve the quality and physicochemical properties of heat-induced gels of FDB. Optimized FDB gels with KG can be used as an innovative food ingredient to fortify nutrition and develop special dietary purposes.
|
38051013
|
Rational Design of Guanidinium-Based Bio-MCOF as a Multifunctional Nanocatalyst in Tumor Cells for Enhanced Chemodynamic Therapy.
|
Chemodynamic therapy (CDT) has emerged as a promising approach to cancer treatment, which can break the intracellular redox state balance and result in severe oxidative damage to biomolecules and organelles with the advantages of being less dependent on external stimulation, having deep tissue-healing abilities, and being resistant to drug resistance. There is considerable interest in developing CDT drugs with high efficiency and low toxicity. In this study, a new guanidinium-based biological metal covalent organic framework (Bio-MCOF), GZHMU-1@Mo, is rationally designed and synthesized as a multifunctional nanocatalyst in tumor cells for enhanced CDT. The DFT calculation and experimental results showed that due to the ability of MoO42- ion to promote electron transfer and increase the redox active site, Cu3 clusters and MoO42- ions in GZHMU-1@Mo can synergistically catalyze the production of reactive oxygen species (ROS) from oxygen and H2O2 in tumor cells, as well as degrade intracellular reducing substances, GSH and NADH, so as to disrupt the redox balance in tumor cells. Moreover, GZHMU-1@Mo exhibits a potent killing effect on tumor cells under both normal oxygen and anaerobic conditions. Further in vitro and in vivo antiproliferation studies revealed that the GZHMU-1@Mo nanoagent displays a remarkable antiproliferation effect and effectively inhibits tumor growth. Taken together, our study provides an insightful reference benchmark for the rational design of Bio-MCOF-based nanoagents with efficient CDT.
|
37899845
|
Inhaled Corticosteroid Exposure and Risk of Cataract in Patients with Asthma and COPD: A Systematic Review and Meta-Analysis.
|
Purpose
Both systemic and inhaled corticosteroids may increase the risk of cataract in patients with both chronic obstructive pulmonary disease (COPD) and asthma. Our aim was to assess the degree of association between cataract and corticosteroid exposure in patients with asthma and COPD.
Methods
A systematic literature review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The odds ratio estimates were extracted from each article. A random effects model was applied for estimate pooling in separate meta-analyses according to study design. Meta-regression was performed to assess the dose-response relationship between corticosteroid exposure and the risk of cataract development.
Results
A total of 19 studies met the criteria for inclusion in this review, of which 12 studies provided effect estimates for pooled analyses. All but one of the included observational studies reported a significant association between use of corticosteroids and cataract development in cohorts of asthma and/or COPD patients. Pooled analyses revealed on average a doubled risk of cataract in corticosteroid-exposed asthma and COPD patients. Studies have shown that daily high-dose inhaled corticosteroid (ICS) ≥ 1000 μg is associated with a significant risk of developing cataract and by that predispose to subsequent cataract surgery, although one study showed that systemic corticosteroids increase cataract risk more than ICS.
Conclusion
ICS treatment in asthma and COPD patients is a risk factor for cataract development. Our results emphasize a previously underestimated potential long-term risk of treatment with ICS and underline the importance of targeting ICS treatment, and not least dosing, to improve the risk-benefit ratio of maintenance treatment in both asthma and COPD.
|
38081263
|
An X-band compact rectangular waveguide TE10-circular waveguide TE01 mode converter.
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This paper proposed an X-band compact efficient rectangular waveguide TE10-circular waveguide TE01 mode converter and conducted its structure design, theoretical analysis, numerical simulation, and experimental research. This mode converter is composed of a rectangular waveguide TE10-TE20 mode converter and a rectangular waveguide TE20-circular waveguide TE01 mode converter. In the design of the rectangular waveguide TE20-circular waveguide TE01 mode converter, a rectangular waveguide step is used to counteract the microwave reflection due to the discontinuity of the rectangular-circular waveguide connection, and two choke slots are involved to suppress the TE21 mode in the circular waveguide by cutting off the axial component of its surface current on the waveguide wall, so as to improve the TE01 mode conversion efficiency. The simulation results show that the reflection coefficient of the mode converter is less than 5% and the TE01 mode conversion efficiency is about 98.4% at the operation frequency of 9.3 GHz. The bandwidth with a transmission coefficient greater than 98% is about 200 MHz. The back-to-back experimental system is demonstrated, and the experimental results show that the measured TE01 mode conversion efficiency is about 98.2%, which is consistent with the simulation result.
|
38081262
|
Dark matter axion search using a Josephson Traveling wave parametric amplifier.
|
We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.
|
37592961
|
Accuracy of 3D printed spine models for pre-surgical planning of complex adolescent idiopathic scoliosis (AIS) in spinal surgeries: a case series.
|
Adolescent idiopathic scoliosis (AIS) is a noticeable spinal deformity in both adult and adolescent population. In majority of the cases, the gold standard of treatment is surgical intervention. Technological advancements in medical imaging and 3D printing have revolutionised the surgical planning and intraoperative decision making for surgeons in spinal surgery. However, its applicability for planning complex spinal surgeries is poorly documented with human subjects. The objective of this study is to evaluate the accuracy of 3D printed models for complex spinal deformities based on Cobb angles between 40° to 95°.This is a retrospective cohort study where, five CT scans of the patients with AIS were segmented and 3D printed for evaluating the accuracy. Consideration was given to the Inter-patient and acquisition apparatus variability of the CT-scan dataset to understand the effect on trueness and accuracy of the developed CAD models. The developed anatomical models were re-scanned for analysing quantitative surface deviation to assess the accuracy of 3D printed spinal models. Results show that the average of the root mean square error (RMSE) between the 3DP models and virtual models developed using CT scan of mean surface deviations for the five 3d printed models was found to be 0.5±0.07 mm. Based on the RMSE, it can be concluded that 3D printing based workflow is accurate enough to be used for presurgical planning for complex adolescent spinal deformities. Image acquisition and post processing parameters, type of 3D printing technology plays key role in acquiring required accuracy for surgical applications.
|
37990691
|
Reproducibility of organ-level effects in repeat dose animal studies.
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This work estimates benchmarks for new approach method (NAM) performance in predicting organ-level effects in repeat dose studies of adult animals based on variability in replicate animal studies. Treatment-related effect values from the Toxicity Reference database (v2.1) for weight, gross, or histopathological changes in the adrenal gland, liver, kidney, spleen, stomach, and thyroid were used. Rates of chemical concordance among organ-level findings in replicate studies, defined by repeated chemical only, chemical and species, or chemical and study type, were calculated. Concordance was 39 - 88%, depending on organ, and was highest within species. Variance in treatment-related effect values, including lowest effect level (LEL) values and benchmark dose (BMD) values when available, was calculated by organ. Multilinear regression modeling, using study descriptors of organ-level effect values as covariates, was used to estimate total variance, mean square error (MSE), and root residual mean square error (RMSE). MSE values, interpreted as estimates of unexplained variance, suggest study descriptors accounted for 52-69% of total variance in organ-level LELs. RMSE ranged from 0.41 - 0.68 log10-mg/kg/day. Differences between organ-level effects from chronic (CHR) and subchronic (SUB) dosing regimens were also quantified. Odds ratios indicated CHR organ effects were unlikely if the SUB study was negative. Mean differences of CHR - SUB organ-level LELs ranged from -0.38 to -0.19 log10 mg/kg/day; the magnitudes of these mean differences were less than RMSE for replicate studies. Finally, in vitro to in vivo extrapolation (IVIVE) was employed to compare bioactive concentrations from in vitro NAMs for kidney and liver to LELs. The observed mean difference between LELs and mean IVIVE dose predictions approached 0.5 log10-mg/kg/day, but differences by chemical ranged widely. Overall, variability in repeat dose organ-level effects suggests expectations for quantitative accuracy of NAM prediction of LELs should be at least ± 1 log10-mg/kg/day, with qualitative accuracy not exceeding 70%.
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37839016
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Agent-based simulations improve abundance estimation.
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Abundance is a fundamental characteristic of every biological population and is the focus of many research programs in ecology and conservation. In this paper I give an overview of the challenges of estimating abundance. I argue that truly understanding, validating, and refining the field techniques and quantitative methods used to estimate abundance can largely benefit from agent-based simulations. I illustrate this through the example of bird point counts and introduce the software bSims to test statistical and biological assumptions for estimating abundance and to aid survey design.
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37532046
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Contribution of land use and cover change (LUCC) to the global terrestrial carbon uptake.
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Terrestrial carbon uptake is critical to the removal of greenhouse gases and mitigation of global warming, which are closely related to land use and cover change (LUCC). However, understanding terrestrial carbon uptake and the LUCC contribution remains unclear because of complex interactions with other drivers (particularly climate change). By proposing an innovative approach of "trajectory analysis", this study aimed to isolate the LUCC contribution to terrestrial carbon uptake over different scales. Methodologically, global land was first divided into sub-regions of land transformations and stable land trajectories. Then, the carbon uptake change in the stable land trajectory was taken as a synthetic influence of climate change, which was used as a reference to isolate the carbon uptake alternation generated from the LUCC contribution in the land transformation trajectories. Finally, future LUCC and the terrestrial carbon uptake response were predicted under different development pathways. The results showed the global mean net ecosystem production (NEP) was 27.44 ± 36.51 g C m-2 yr-1 in the past two decades (2001-2019), generating 3.15 ± 0.88 Pg C yr-1 of the total terrestrial carbon uptake. Both the NEP and total carbon uptake showed significant increasing trends. Specifically, the mean NEP increased from 17.96 g C m-2 yr-1 in 2001 to 37.37 g C m-2 yr-1 in 2019, with the trend written as y = 1.20× + 15.20 (R2 = 0.62, p < 0.01). Meanwhile, the total carbon uptake increased from 2.35 Pg C yr-1 in 2001 to 4.13 Pg C yr-1 in 2019, which could be written as y = 0.12× + 1.93 (R2 = 0.56, p < 0.01). Climate change acted as the dominant factor for the trends at the global scale, which contributed 21.26 g C m-2 yr-1 and 1.59 Pg C yr-1 of the mean NEP and total carbon uptake changes in the stable land trajectories (94.30 million km2 that covered 63.29 % of the global land area), and the historical LUCC contributed -6.30 g C m-2 yr-1 (-40.85 %) and - 0.046 Pg C yr-1 (-57.50 %) of the mean NEP and the total carbon uptake change in the land transformation trajectories (6.64 million km2 that covered 4.46 % of the global land area), respectively. The maximum LUCC contribution (-61.85 g C m-2 yr-1) to the mean NEP occurred in the land transformations from evergreen needleleaf forests to woody savannas, while the maximum contribution (-0.034 Pg C y-1) to total carbon uptake was in the deforested regions from evergreen broadleaf forests to woody savannas. Eight SSP-RCP scenarios predictions demonstrated that future terrestrial carbon uptake would increase by an average of 0.015 Pg C yr-1 in 2100 due to global afforestation. SSP4-3.4 and SSP5-3.4 had the greatest potential for increasing carbon uptake, which is expected to reach a maximum increase (0.045 Pg C yr-1) in 2100. In contrast, the minimum terrestrial carbon uptake would occur in SSP5-8.5, which had the highest CO2 emissions. In conclusion, although relatively limited at the global scale, LUCC (particularly forest change) exerted an unneglectable role on terrestrial carbon uptake in land transformation regions. The results of this study will help to clarify terrestrial carbon uptake dynamics and provide a basis for carbon neutral and climatic adaptation.
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37532047
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Raman Microspectroscopy evidence of microplastics in human semen.
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The presence of microplastics (MPs) in human fluids and organs is a great concern, since, as highlighted by recent studies on animal models, they could cause alterations of several physiological functions, including reproduction. In this study, semen samples collected from men living in a polluted area of the Campania Region (Southern Italy), were analyzed to assess the presence of MPs. N. 16 pigmented microplastic fragments (ranging from 2 to 6 μm in size) with spheric or irregular shapes were found in six out of ten samples. All the detected MPs were characterized in terms of morphology (size, colour, and shape) and chemical composition by Raman Microspectroscopy. Chemical composition showed the presence of polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), polyvinylchloride (PVC), polycarbonate (PC), polyoxymethylene (POM) and acrylic, suggesting ingestion and/or inhalation as a route of exposure to environmental MPs. In this work, we propose for the first time a mechanism by which MPs pass into the semen most likely through the epididymis and seminal vesicles, which are the most susceptible to inflammation.
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37775818
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Multi-omic insights into the formation and evolution of a novel shell microstructure in oysters.
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BACKGROUND
Molluscan shell, composed of a diverse range of architectures and microstructures, is a classic model system to study the relationships between molecular evolution and biomineralized structure formation. The shells of oysters differ from those of other molluscs by possessing a novel microstructure, chalky calcite, which facilitates adaptation to the sessile lifestyle. However, the genetic basis and evolutionary origin of this adaptive innovation remain largely unexplored.
RESULTS
We report the first whole-genome assembly and shell proteomes of the Iwagaki oyster Crassostrea nippona. Multi-omic integrative analyses revealed that independently expanded and co-opted tyrosinase, peroxidase, TIMP genes may contribute to the chalky layer formation in oysters. Comparisons with other molluscan shell proteomes imply that von Willebrand factor type A and chitin-binding domains are basic members of molluscan biomineralization toolkit. Genome-wide identification and analyses of these two domains in 19 metazoans enabled us to propose that the well-known Pif may share a common origin in the last common ancestor of Bilateria. Furthermore, Pif and LamG3 genes acquire new genetic function for shell mineralization in bivalves and the chalky calcite formation in oysters likely through a combination of gene duplication and domain reorganization.
CONCLUSIONS
The spatial expression of SMP genes in the mantle and molecular evolution of Pif are potentially involved in regulation of the chalky calcite deposition, thereby shaping the high plasticity of the oyster shell to adapt to a sessile lifestyle. This study further highlights neo-functionalization as a crucial mechanism for the diversification of shell mineralization and microstructures in molluscs, which may be applied more widely for studies on the evolution of metazoan biomineralization.
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37775827
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A microglial activity state biomarker panel differentiates FTD-granulin and Alzheimer's disease patients from controls.
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BACKGROUND
With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.
METHODS
Using mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), genetically modified to yield the most opposite homeostatic (TREM2-knockout) and disease-associated (GRN-knockout) states, we identified microglia activity-dependent markers. Non-targeted mass spectrometry was used to identify proteomic changes in microglia and cerebrospinal fluid (CSF) of Grn- and Trem2-knockout mice. Additionally, we analyzed the proteome of GRN- and TREM2-knockout hiMGL and their conditioned media. Candidate marker proteins were tested in two independent patient cohorts, the ALLFTD cohort (GRN mutation carriers versus non-carriers), as well as the proteomic data set available from the EMIF-AD MBD study.
RESULTS
We identified proteomic changes between the opposite activation states in mouse microglia and CSF, as well as in hiMGL cell lysates and conditioned media. For further verification, we analyzed the CSF proteome of heterozygous GRN mutation carriers suffering from frontotemporal dementia (FTD). We identified a panel of six proteins (FABP3, MDH1, GDI1, CAPG, CD44, GPNMB) as potential indicators for microglial activation. Moreover, we confirmed three of these proteins (FABP3, GDI1, MDH1) to be significantly elevated in the CSF of Alzheimer's (AD) patients. Remarkably, each of these markers differentiated amyloid-positive cases with mild cognitive impairment (MCI) from amyloid-negative individuals.
CONCLUSIONS
The identified candidate proteins reflect microglia activity and may be relevant for monitoring the microglial response in clinical practice and clinical trials modulating microglial activity and amyloid deposition. Moreover, the finding that three of these markers differentiate amyloid-positive from amyloid-negative MCI cases in the AD cohort suggests that these proteins associate with a very early immune response to seeded amyloid. This is consistent with our previous findings in the Dominantly Inherited Alzheimer's Disease Network (DIAN) cohort, where soluble TREM2 increases as early as 21 years before symptom onset. Moreover, in mouse models for amyloidogenesis, seeding of amyloid is limited by physiologically active microglia further supporting their early protective role. The biological functions of some of our main candidates (FABP3, CD44, GPNMB) also further emphasize that lipid dysmetabolism may be a common feature of neurodegenerative disorders.
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38051030
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The history and future of population pharmacokinetic analysis in drug development.
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1. The analysis of pharmacokinetic data has been in a constant state of evolution since the introduction of the term pharmacokinetics. Early work focused on mechanistic understanding of the absorption, distribution, metabolism and excretion of drug products.2. The introduction of non-linear mixed effects models to perform population pharmacokinetic analysis initiated a paradigm shift. The application of these models represented a major shift in evaluating variability in pharmacokinetic parameters across a population of subjects.3. While technological advancements in computing power have feuled the growth of population pharmacokinetics in drug development efforts, there remain many challenges in reducing the time required to incorporate these learnings into a model-informed development process. These challenges exist because of expanding datasets, increased number of diagnostics, and more complex mathematical models.4. New machine learning tools may be potential solutions for these challenges. These new methodologies include genetic algorithms for model selection, machine learning algorithms for covariate selection, and deep learning models for pharmacokinetic and pharmacodynamic data. These new methods promise the potential for less bias, faster analysis times, and the ability to integrate more data.5. While questions remain regarding the ability of these models to extrapolate accurately, continued research in this area is expected to address these questions.
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38051031
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Efficient Interfacial Sites between Metallic and Oxidized Cobalt for Propene Hydroformylation.
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Currently, the hydroformylation of short olefins is operated almost exclusively by using Rh catalysts. Considering the high cost and scarcity of rhodium resources, it is important to develop non-noble metal catalysts toward hydroformylation. Herein, we report an efficient cobalt-based catalyst rich in interfacial sites between metallic and oxidized cobalt species for the hydroformylation of short olefin, propene, under a moderate syngas pressure. The catalyst exhibited a high specific activity of 252 mol molCo-1 h-1 in toluene under 2 bar of propene and 40 bar of CO/H2 mixed gas (CO/H2 = 1:1) at 160 °C. According to mechanistic studies, the interface of metallic and oxidized cobalt species promoted the adsorption of CO and propene. Moreover, the interfacial sites lowered the energy barrier for CO* hydrogenation and C-C coupling compared with metallic cobalt.
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38051032
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Dual Ratiometric Fluorescence Monitoring of Mechanical Polymer Chain Stretching and Subsequent Strain-Induced Crystallization.
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Tracking the behavior of mechanochromic molecules provides valuable insights into force transmission and associated microstructural changes in soft materials under load. Herein, we report a dual ratiometric fluorescence (FL) analysis for monitoring both mechanical polymer chain stretching and strain-induced crystallization (SIC) of polymers. SIC has recently attracted renewed attention as an effective mechanism for improving the mechanical properties of polymers. A polyurethane (PU) film incorporating a trace of a dual-emissive flapping force probe (N-FLAP, 0.008 wt %) exhibited a blue-to-green FL spectral change in a low-stress region (<20 MPa), resulting from conformational planarization of the probe in mechanically stretched polymer chains. More importantly, at higher probe concentrations (∼0.65 wt %), the PU film showed a second spectral change from green to yellow during the SIC growth (20-65 MPa) due to self-absorption of scattered FL in a short wavelength region. The reversibility of these spectral changes was demonstrated by load-unload cycles. With these results in hand, the degrees of the polymer chain stretching and the SIC were quantitatively mapped and monitored by dual ratiometric imaging based on different FL ratios (I525/I470 and I525/I600). Simultaneous analysis of these two mappings revealed a spatiotemporal gap in the distribution of the polymer chain stretching and the SIC. The combinational use of the dual-emissive force probe and the ratiometric FL imaging is a universal approach for the development of soft matter physics.
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38051033
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Suicide Among Adults Age 55 and Older, 2021.
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Suicide is a leading cause of mortality in the United States, with an ageadjusted rate of 14.1 deaths per 100,000 population in 2021 (1). Older adults tend to have higher rates of suicide, although they represent a low percentage of the total number of suicides (2). Factors that specifically affect older adults can include declines in physical and cognitive functioning, changes in mental health, and other factors often associated with getting older, like bereavement, loneliness, and lack of social connectedness (3-8). This report presents suicide rates for adults age 55 and older by sex and mechanism of suicide.
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