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Two new polythioamides were prepared through the polycondensation reaction between thiourea monomers and terephthaloyl dichloride, while the thiourea monomers were synthesized by the interaction of aromatic (4,4'-diaminophenylsulfone) or alicyclic (1,2-cyclohexanediamine) diamine with ammonium thiocyanate. The elemental composition of polythioamides was confirmed through CHN microanalysis. The structure and properties of thiourea monomers and polythioamides were determined through proton NMR, UV-Vis, FT-IR spectroscopy, fluorescence, TGA/DTA and SEM. The polythioamides indicated high thermal stabilities which were assessed from their Tmax (temperature indicating highest rate of weight loss) values (670 °C and 346 °C) observed in their DTG graphs. The thioureas and polythioamides were fluorescent and showed multicolor (violet, green, yellow, orange and red) emissions at different excitation wavelengths. All the synthesized compounds were also tested for their antifungal and antibacterial functions and showed antibacterial activity against Salmonella typhi, Bacillus subtilis and Staphylococcus aureus, and antifungal activity against Candida albicans.

Objective: To study the impact of neonatal hypoglycemia on neurodevelopment and neuro-developmental clusters at 18 months of age., Methods: This prospective cohort study was conducted at the pediatric and neonatal wards of a tertiary care hospital. Study subjects were neonates with hypoglycemia (blood sugar <47 mg/dL at presentation). Enrolled babies were evaluated at 3,6,9,12 and 18 months for overall neurodevelopment and neurodevelopmental clusters by Developmental Assessment Scale for Indian Infants (DASII)., Results: Of the total 259 neonates with hypoglycemia, 92 met the inclusion criteria, and 85 babies could be evaluated at 3,6,9,12 and 18 months. 20 (23.5%) neonates had asymptomatic hypoglycemia, and 7 (8.2%) had symptoms with seizures. 17.6% (n=15) babies had delayed development quotient for development at 3 months of life. At 18 months of age, 9.4% (n=8) subjects had delayed development quotient for motor clusters and 7% (n=6) had delayed development quotient for mental clusters. Positive correlation was found between age and both improvement in motor development (r=0.99, P<0.05) and mental development (r=0.95, P<0.05) clusters., Conclusion: Motor and mental developmental clusters are affected by neonatal hypoglycemia. Improvement in developmental clusters occurs with increasing age.

Graduate medical education in radiology serves an imperative role in training the next generation of specialists. Given the regularity of virtual interviews, the website of a fellowship programs remains a critical first-line source of information of applicants. The aim of this study is to systematically evaluate 7 radiology fellowship programs utilizing a systematic process. A cross-sectional descriptive 286 graduate medical education fellowship programs in radiology were screened from the Fellowship and Residency Electronic Interactive Database (FREIDA). Extracted data was evaluated for comprehensiveness using 20 content criteria, and a readability score is calculated. The mean comprehensiveness among all fellowship program websites was 55.8% (n = 286), and the average FRE among the program overview sections was 11.9 (n = 214). ANOVA revealed no statistical significance in program website comprehensiveness between radiology fellowships (P = 0.33). The quality of a program's website data continues to serve an important role in an applicant's decision-making. Fellowship programs have improved in their content availability overtime, but content reevaluation needs to be continued for tangible improvement., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Few studies examined blood biomarkers informative of patient-reported outcome (PRO) of disability in people with multiple sclerosis (MS). We examined the associations between serum multi-protein biomarker profiles and patient-reported MS disability. In this cross-sectional study (2017-2020), adults with diagnosis of MS (or precursors) from two independent clinic-based cohorts were divided into a training and test set. For predictors, we examined seven clinical factors (age at sample collection, sex, race/ethnicity, disease subtype, disease duration, disease-modifying therapy [DMT], and time interval between sample collection and closest PRO assessment) and 19 serum protein biomarkers potentially associated with MS disease activity endpoints identified from prior studies. We trained machine learning (ML) models (Least Absolute Shrinkage and Selection Operator regression [LASSO], Random Forest, Extreme Gradient Boosting, Support Vector Machines, stacking ensemble learning, and stacking classification) for predicting Patient Determined Disease Steps (PDDS) score as the primary endpoint and reported model performance using the held-out test set. The study included 431 participants (mean age 49 years, 81% women, 94% non-Hispanic White). For binary PDDS score, combined feature input of routine clinical factors and the 19 proteins consistently outperformed base models (comprising clinical features alone or clinical features plus one single protein at a time) in predicting severe (PDDS ≥ 4) versus mild/moderate (PDDS < 4) disability across multiple machine learning approaches, with LASSO achieving the best area under the curve (AUC PDDS = 0.91) and other metrics. For ordinal PDDS score, LASSO model comprising combined clinical factors and 19 proteins as feature input ( R 2 PDDS = 0.31) again outperformed base models. The two best-performing LASSO models ( i.e. , binary and ordinal PDDS score) shared six clinical features (age, sex, race/ethnicity, disease subtype, disease duration, DMT efficacy) and nine proteins (cluster of differentiation 6, CUB-domain-containing protein 1, contactin-2, interleukin-12 subunit-beta, neurofilament light chain [NfL], protogenin, serpin family A member 9, tumor necrosis factor superfamily member 13B, versican). By comparison, LASSO models with clinical features plus one single protein at a time as feature input did not select either NfL or glial fibrillary acidic protein (GFAP) as a final feature. Forcing either NfL or GFAP as a single protein feature into models did not improve performance beyond clinical features alone. Stacking classification model using five functional pathways to represent multiple proteins as meta-features implicated those involved in neuroaxonal integrity as significant contributors to predictive performance. Thus, serum multi-protein biomarker profiles improve the prediction of real-world MS disability status beyond clinical profile alone or clinical profile plus single protein biomarker, reaching clinically actionable performance., Competing Interests: Sample collection and biomarker assay were funded in part by Octave Bioscience. Z.X. serves on the scientific advisory board of Roche/Genentech and has a research agreement with Octave Biosciences. W,Z. serves on the scientific advisory board of Roche/Genentech. J.F.F. has received research support from Biogen, Novartis, Adamas, Octave and Genentech. He received speakers’ honoraria from Biogen. He has participated in advisory boards with TG Therapeutics, Sandoz, Biogen and Octave. He has equity interest in Octave. He is the founder of InterPro Bioscience. F.Q. is an employee of Octave Bioscience Inc. F.Z. was an employee of Octave Bioscience Inc, when the study analysis was performed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The exponential growth of artificial intelligence (AI) has allowed for its integration into multiple sectors, including, notably, healthcare. Chatbots have emerged as a pivotal resource for improving patient outcomes and assisting healthcare practitioners through various AI-based technologies. In critical care, kidney-related conditions play a significant role in determining patient outcomes. This article examines the potential for integrating chatbots into the workflows of critical care nephrology to optimize patient care. We detail their specific applications in critical care nephrology, such as managing acute kidney injury, alert systems, and continuous renal replacement therapy (CRRT); facilitating discussions around palliative care; and bolstering collaboration within a multidisciplinary team. Chatbots have the potential to augment real-time data availability, evaluate renal health, identify potential risk factors, build predictive models, and monitor patient progress. Moreover, they provide a platform for enhancing communication and education for both patients and healthcare providers, paving the way for enriched knowledge and honed professional skills. However, it is vital to recognize the inherent challenges and limitations when using chatbots in this domain. Here, we provide an in-depth exploration of the concerns tied to chatbots' accuracy, dependability, data protection and security, transparency, potential algorithmic biases, and ethical implications in critical care nephrology. While human discernment and intervention are indispensable, especially in complex medical scenarios or intricate situations, the sustained advancements in AI signal that the integration of precision-engineered chatbot algorithms within critical care nephrology has considerable potential to elevate patient care and pivotal outcome metrics in the future.

Objective:  This study aims to audit the process of patient management with aerosol-generating procedure (ultrasonic scaling) while adherence to the guidelines for health care workers (HCWs) during the coronavirus disease 2019 (COVID-19)., Materials and Methods:  Audits records at the Department of Periodontology at University College of Medicine and Dentistry Hospital, Lahore, Pakistan were collected (prospectively) over the period of October 1 to November 30, 2020 (1st cycle) and December 14, 2020 to February 12, 2021 (2nd cycle). The audit was divided into three components based on the guidelines: (1) physical environment, (2) patients/appointments, and (3) COVID standard operating procedures related to HCWs., Results:  The recommended physical layout and procedural factors, as suggested by the guidelines for dental clinics, were observed during the first cycle of audit, and discrepancy of ventilation system was fixed after the first cycle. Audit team reported the observance of fallow time three times daily, which revealed 83.3% observance of fallow time.Later in the second cycle when the extraoral high-volume air evacuator was installed, the fallow time was reduced to 15 minutes and not only five procedural slots per day were created but fallow time was also observed 100% of the time., Conclusion:  Following the standard guidelines resulted in more efficient working environment and lesser risk for HCWs while performing aerosol-generating procedures., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background and Objectives: Literature reviews are foundational to understanding medical evidence. With AI tools like ChatGPT, Bing Chat and Bard AI emerging as potential aids in this domain, this study aimed to individually assess their citation accuracy within Nephrology, comparing their performance in providing precise., Materials and Methods: We generated the prompt to solicit 20 references in Vancouver style in each 12 Nephrology topics, using ChatGPT, Bing Chat and Bard. We verified the existence and accuracy of the provided references using PubMed, Google Scholar, and Web of Science. We categorized the validity of the references from the AI chatbot into (1) incomplete, (2) fabricated, (3) inaccurate, and (4) accurate., Results: A total of 199 (83%), 158 (66%) and 112 (47%) unique references were provided from ChatGPT, Bing Chat and Bard, respectively. ChatGPT provided 76 (38%) accurate, 82 (41%) inaccurate, 32 (16%) fabricated and 9 (5%) incomplete references. Bing Chat provided 47 (30%) accurate, 77 (49%) inaccurate, 21 (13%) fabricated and 13 (8%) incomplete references. In contrast, Bard provided 3 (3%) accurate, 26 (23%) inaccurate, 71 (63%) fabricated and 12 (11%) incomplete references. The most common error type across platforms was incorrect DOIs., Conclusions: In the field of medicine, the necessity for faultless adherence to research integrity is highlighted, asserting that even small errors cannot be tolerated. The outcomes of this investigation draw attention to inconsistent citation accuracy across the different AI tools evaluated. Despite some promising results, the discrepancies identified call for a cautious and rigorous vetting of AI-sourced references in medicine. Such chatbots, before becoming standard tools, need substantial refinements to assure unwavering precision in their outputs.

Patient education has been transformed using digital media and online repositories which disseminate information with greater efficiency. In dermatology, this transformation has allowed for patients to gain education on common cutaneous conditions and improve health literacy. Xanthelasma palpebrarum is one of the most common cutaneous conditions, yet there is a poor understanding of how digital materials affect health literacy on this condition. Our study aimed to address this paucity of literature utilizing Brief DISCERN, Rothwell's Classification of Questions, and six readability calculations. The findings of this study indicate a poor-quality profile (Brief DISCERN < 16) regarding digital materials and readability scores which do not meet grade-level recommendations in the United States. This indicates a need to improve the current body of educational materials used by clinicians for diagnosing and managing xanthelasma palpebrarum.

Patients with chronic kidney disease (CKD) necessitate specialized renal diets to prevent complications such as hyperkalemia and hyperphosphatemia. A comprehensive assessment of food components is pivotal, yet burdensome for healthcare providers. With evolving artificial intelligence (AI) technology, models such as ChatGPT, Bard AI, and Bing Chat can be instrumental in educating patients and assisting professionals. To gauge the efficacy of different AI models in discerning potassium and phosphorus content in foods, four AI models-ChatGPT 3.5, ChatGPT 4, Bard AI, and Bing Chat-were evaluated. A total of 240 food items, curated from the Mayo Clinic Renal Diet Handbook for CKD patients, were input into each model. These items were characterized by their potassium (149 items) and phosphorus (91 items) content. Each model was tasked to categorize the items into high or low potassium and high phosphorus content. The results were juxtaposed with the Mayo Clinic Renal Diet Handbook's recommendations. The concordance between repeated sessions was also evaluated to assess model consistency. Among the models tested, ChatGPT 4 displayed superior performance in identifying potassium content, correctly classifying 81% of the foods. It accurately discerned 60% of low potassium and 99% of high potassium foods. In comparison, ChatGPT 3.5 exhibited a 66% accuracy rate. Bard AI and Bing Chat models had an accuracy rate of 79% and 81%, respectively. Regarding phosphorus content, Bard AI stood out with a flawless 100% accuracy rate. ChatGPT 3.5 and Bing Chat recognized 85% and 89% of the high phosphorus foods correctly, while ChatGPT 4 registered a 77% accuracy rate. Emerging AI models manifest a diverse range of accuracy in discerning potassium and phosphorus content in foods suitable for CKD patients. ChatGPT 4, in particular, showed a marked improvement over its predecessor, especially in detecting potassium content. The Bard AI model exhibited exceptional precision for phosphorus identification. This study underscores the potential of AI models as efficient tools in renal dietary planning, though refinements are warranted for optimal utility.

Objectives: Palliative sedation (PS) and Medical Assistance in Dying (MAiD) are options for end-of-life (EOL) care in Canada, since the latter was legalized in 2016. Little research to date has explored the potential impact of MAiD on PS practices. This study investigated physicians' perceptions of their practices surrounding PS and how they may have changed since 2016., Methods: A survey ( n =37) and semi-structured interviews ( n =23) were conducted with palliative care providers throughout Ontario. Questions focused on PS practices and explored potential changes following the implementation of MAiD. Codes were determined collaboratively and applied line-by-line by 2 independent investigators. Survey responses were analyzed alongside interview transcripts and noted to be concordant. Themes were generated via reflexive thematic analysis., Results: Thematic analysis yielded the following themes: (1) Increased patient/family knowledge of EOL care; (2) More frequent/fulsome discussions; (3) Normalization/repositioning of PS; and (4) Conflation and differentiation of PS/MAiD. Across these themes, participants espoused increased patient, family, and provider comfort with PS, which may stem equally from the advent of MAiD and the growth of palliative care in general. Participants also emphasized that, following MAiD, PS is viewed as a less radical intervention., Significance of Results: This is the first study to investigate physicians' perspectives on the impact of MAiD on PS. Participants strongly opposed treating MAiD and PS as direct equivalents, given the differences in intent and eligibility. Participants stressed that MAiD requests/inquiries should prompt individualized assessments exploring all avenues of symptom management - the results of which may or may not include PS.

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients., Competing Interests: Declaration of Competing Interest Tanuja Chitnis has received compensation for consulting from Biogen, Novartis Pharmaceuticals, Roche Genentech, and Sanofi Genzyme, and has received research support from the National Institutes of Health, National MS Society, US Department of Defense, EMD Serono, I-Mab Biopharma, Mallinckrodt ARD, Novartis Pharmaceuticals, Octave Bioscience, Inc., Roche Genentech, and Tiziana Life Sciences. This research was conducted in part with the support of the Department of Defense through the Multiple Sclerosis Research Program under Award No. W81XWH-18-1-0648 (to T. Chitnis). John Foley has received research support from Biogen, Novartis, Adamas, Octave Bioscience, Inc., Genentech, and Mallinckrodt, has received speakers' honoraria and acted as a consultant for EMD Serono, Genzyme, Novartis, Biogen, and Genentech, has equity interest in Octave Bioscience, Inc., and is the founder of InterPro Bioscience. Carolina Ionete has received research support from Biogen, Serono, Genentech, NMSS, and the Department of Defense, and received compensation for advisory board activity from Sanofi-Genzyme. Nabil K. El Ayoubi has received support to attend scientific educational courses from Novartis, Merck Serono, Sanofi, Biologix, and has received speaker honoraria for scientific presentations on Multiple Sclerosis from Biologix, Sanofi, Merck Serono, and Novartis. Shrishti Saxena, Patricia Gaitan-Walsh, Anu Paul, and Fermisk Saleh have no disclosures. Hrishikesh Lokhande has received research support from the US Department of Defense and Octave Bioscience, Inc. Howard Weiner has received research support from the Department of Defense, Genentech, Inc., National Institutes of Health, National Multiple Sclerosis Society, Novartis, and Sanofi Genzyme. He has received compensation for consulting from Genentech, Inc., IM Therapeutics, IMAB Biopharma, MedDay Pharmaceuticals, Tiziana Life Sciences, and vTv Therapeutics. Ferhan Qureshi, Anisha Keshavan, Kian Jalaleddini, and Ati Ghoreyshi are employees of Octave Bioscience, Inc. Michael J. Becich, Fatima Rubio da Costa, Victor M. Gehman, and Fujun Zhang were employees of Octave Bioscience, Inc., at the time the study was completed. Samia J. Khoury has received compensation for scientific advisory board activity from Merck and Roche and for serving on IDMC for Biogen., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Hydrogen (H 2 ) is a possible energy transporter and feedstock for energy decarbonization, transportation, and chemical sectors while reducing global warming's consequences. The predominant commercial method for producing H 2 today is steam methane reforming (SMR). However, there is still room for development in process intensification, energy optimization, and environmental concerns related to CO 2 emissions. Reactors using metallic membranes (MRs) can handle both problems. Compared to traditional reactors, MRs operates at substantially lower pressures and temperatures. As a result, capital and operational costs may be significantly cheaper than traditional reactors. Furthermore, metallic membranes (MMs), particularly Pd and its alloys, naturally permit only H 2 permeability, enabling the production of a stream with a purity of up to 99.999%. This review describes several methods for H 2 production based on the energy sources utilized. SRM with CO 2 capture and storage (CCUS), pyrolysis of methane, and water electrolysis are all investigated as process technologies. A debate based on a color code was also created to classify the purity of H 2 generation. Although producing H 2 using fossil fuels is presently the least expensive method, green H 2 generation has the potential to become an affordable alternative in the future. From 2030 onward, green H 2 is anticipated to be less costly than blue hydrogen. Green H 2 is more expensive than fossil-based H 2 since it uses more energy. Blue H 2 has several tempting qualities, but the CCUS technology is pricey, and blue H 2 contains carbon. At this time, almost 80-95% of CO 2 can be stored and captured by the CCUS technology. Nanomaterials are becoming more significant in solving problems with H 2 generation and storage. Sustainable nanoparticles, such as photocatalysts and bio-derived particles, have been emphasized for H 2 synthesis. New directions in H 2 synthesis and nanomaterials for H 2 storage have also been discussed. Further, an overview of the H 2 value chain is provided at the end, emphasizing the financial implications and outlook for 2050, i.e., carbon-free H 2 and zero-emission H 2 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Blood-based biomarkers can be economic and easily accessible tools for monitoring and predicting disease activity in multiple sclerosis. The objective of this study was to determine the predictive value of a multivariate proteomic assay for concurrent and future microstructural/axonal brain pathology in a longitudinal study of a heterogeneous group of people with multiple sclerosis. A proteomic analysis was obtained on serum samples from 202 people with multiple sclerosis (148 relapsing-remitting and 54 progressive) at baseline and 5-year follow-up. The concentration of 21 proteins related to multiple pathways of multiple sclerosis pathophysiology was derived using Proximity Extension Assay on the Olink platform. Patients were imaged on the same 3T MRI scanner at both timepoints. Тhe rate of whole brain, white matter and grey matter atrophy over the 5-year follow-up was determined using the multi-timepoint Structural Image Evaluation, using Normalisation, of Atrophy algorithms. Lesion burden measures were also assessed. The severity of microstructural axonal brain pathology was quantified using diffusion tensor imaging. Fractional anisotropy and mean diffusivity of normal-appearing brain tissue, normal-appearing white matter, grey matter, T2 and T1 lesions were calculated. Age, sex and body mass index-adjusted step-wise regression models were used. Glial fibrillary acidic protein was the most common and highest-ranked proteomic biomarker associated with greater concurrent microstructural central nervous system alterations ( P < 0.001). The rate of whole brain atrophy was associated with baseline levels of glial fibrillary acidic protein, protogenin precursor, neurofilament light chain and myelin oligodendrocyte ( P < 0.009), whereas grey matter atrophy was associated with higher baseline neurofilament light chain, higher osteopontin and lower protogenin precursor levels ( P < 0.016). Higher baseline glial fibrillary acidic protein level was a significant predictor of future severity of the microstructural CNS alterations as measured by normal-appearing brain tissue fractional anisotropy and mean diffusivity (standardized β = -0.397/0.327, P < 0.001), normal-appearing white matter fractional anisotropy (standardized β = -0.466, P < 0.0012), grey matter mean diffusivity (standardized β = 0.346, P < 0.011) and T2 lesion mean diffusivity (standardized β = 0.416, P < 0.001) at the 5-year follow-up. Serum levels of myelin-oligodendrocyte glycoprotein, neurofilament light chain, contactin-2 and osteopontin proteins were additionally and independently associated with worse concomitant and future axonal pathology. Higher glial fibrillary acidic protein levels were associated with future disability progression (Exp(B) = 8.65, P = 0.004). Multiple proteomic biomarkers are independently associated with greater severity of axonal brain pathology as measured by diffusion tensor imaging in multiple sclerosis. Baseline serum glial fibrillary acidic protein levels can predict future disability progression., Competing Interests: D.J. and N.B. have nothing to disclose. F.Q., V.G., A.K. and K.L. are employees of Octave Bioscience. M.R. received research funding from the National Multiple Sclerosis Society, Department of Defense and National Institute of Neurological Diseases and Stroke. M.G.D. received compensation from Keystone Heart for consultant fees. He received financial support for research activities from Bristol Myers Squibb, Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical. B.W.-G. received honoraria for serving in advisory boards and educational programmes from Biogen Idec, Novartis, Genentech, Genzyme and Sanofi, Janssen, Abbvie and Bayer. She also received support for research activities from the National Institutes of Health, National Multiple Sclerosis Society, Department of Defense, Biogen Idec, Novartis, Genentech, Genzyme and Sanofi. R.Z. has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Keystone Heart, Protembis and Novartis for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Context: Excess calories from free sugars are implicated in the epidemics of obesity and type 2 diabetes. Honey is a free sugar but is generally regarded as healthy., Objective: The effect of honey on cardiometabolic risk factors was assessed via a systematic review and meta-analysis of controlled trials using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach., Data Sources: MEDLINE, Embase, and the Cochrane Library databases were searched up to January 4, 2021, for controlled trials ≥1 week in duration that assessed the effect of oral honey intake on adiposity, glycemic control, lipids, blood pressure, uric acid, inflammatory markers, and markers of nonalcoholic fatty liver disease., Data Extraction: Independent reviewers extracted data and assessed risk of bias. Data were pooled using the inverse variance method and expressed as mean differences (MDs) with 95%CIs. Certainty of evidence was assessed using GRADE., Data Analysis: A total of 18 controlled trials (33 trial comparisons, N = 1105 participants) were included. Overall, honey reduced fasting glucose (MD = -0.20 mmol/L, 95%CI, -0.37 to -0.04 mmol/L; low certainty of evidence), total cholesterol (MD = -0.18 mmol/L, 95%CI, -0.33 to -0.04 mmol/L; low certainty), low-density lipoprotein cholesterol (MD = -0.16 mmol/L, 95%CI, -0.30 to -0.02 mmol/L; low certainty), fasting triglycerides (MD = -0.13 mmol/L, 95%CI, -0.20 to -0.07 mmol/L; low certainty), and alanine aminotransferase (MD = -9.75 U/L, 95%CI, -18.29 to -1.21 U/L; low certainty) and increased high-density lipoprotein cholesterol (MD = 0.07 mmol/L, 95%CI, 0.04-0.10 mmol/L; high certainty). There were significant subgroup differences by floral source and by honey processing, with robinia honey, clover honey, and raw honey showing beneficial effects on fasting glucose and total cholesterol., Conclusion: Honey, especially robinia, clover, and unprocessed raw honey, may improve glycemic control and lipid levels when consumed within a healthy dietary pattern. More studies focusing on the floral source and the processing of honey are required to increase certainty of the evidence., Systematic Review Registration: PROSPERO registration number CRD42015023580., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Vigna is a unique genus that consist of multiple crop species that are domesticated in parallel fashion between 7-10 thousand years ago. Here we studied the evolution of nucleotide-binding site leucine-rich repeat receptor (NLR) genes across five crop species of genus Vigna . In total identified 286, 350, 234, 250, 108 and 161 NLR genes were from Phaseolous vulgaris , Vigna. unguiculata , Vigna mungo , Vigna radiata , Vigna angularis and Vigna umbellata respectively. Comprehensive phylogenetic and clusterization analysis reveals the presence of seven subgroups of Coiled coil like NLRs (CC-NLR) genes and four distinct lineages of Toll interleukin receptor like NLRs (TIR-NLR). Subgroup CC G10 -NLR shows large scale diversification among Vigna species suggesting genus specific distinct duplication pattern in Vigna species. Mainly birth of new NLR gene families and higher rate of terminal duplication is the major determinants for expansion of NLRome in genus Vigna . Recent expansion of NLRome in V. anguiculata and V. radiata was also observed which might suggest that domestication have supported their duplication of lineage specific NLR genes. In short, large scale difference in the architecture of NLRome were observed in diploid plant species. Our findings allowed us to hypothesized that independent parallel domestication is the major drivers of highly divergent evolution of NLRome in genus Vigna .

Purpose: To characterize and analytically validate the MSDA Test, a multi-protein, serum-based biomarker assay developed using Olink ® PEA methodology., Experimental Design: Two lots of the MSDA Test panel were manufactured and subjected to a comprehensive analytical characterization and validation protocol to detect biomarkers present in the serum of patients with multiple sclerosis (MS). Biomarker concentrations were incorporated into a final algorithm used for calculating four Disease Pathway scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and an overall Disease Activity score., Results: Analytical characterization demonstrated that the multi-protein panel satisfied the criteria necessary for a fit-for-purpose validation considering the assay's intended clinical use. This panel met acceptability criteria for 18 biomarkers included in the final algorithm out of 21 biomarkers evaluated. VCAN was omitted based on factors outside of analytical validation; COL4A1 and GH were excluded based on imprecision and diurnal variability, respectively. Performance of the four Disease Pathway and overall Disease Activity scores met the established acceptability criteria., Conclusions and Clinical Relevance: Analytical validation of this multi-protein, serum-based assay is the first step in establishing its potential utility as a quantitative, minimally invasive, and scalable biomarker panel to enhance the standard of care for patients with MS., (© 2023 The Authors. Proteomics - Clinical Applications published by Wiley-VCH GmbH.)

Objective: To determine the association between periodontal disease and low birth weight among pregnant women., Methods: Data for this case-control study was collected from June 2019 till February 2020. All women in the Gynecology Department of Lady Willingdon Hospital, Lahore, who had delivered a baby within the last 24 h were invited to participate. Women who delivered babies less than 2.5 kg were considered as 'cases' (having low birth weight - LBW - infants) and those having babies of 2.5 kg or more were categorized as 'controls' (normal birth weight infants). The selected sample was matched for age, general health (indicated by mean upper arm circumference) and Hemoglobin levels. Intraoral examination was conducted and gingival color and appearance; calculus, bleeding on probing, CPITN (Community Periodontal Index of Treatment Needs) and CAL (clinical attachment loss) were recorded. A binary logistic regression analysis was conducted to determine the predictors of LBW infants. The predictors were further confirmed by applying chi-squared test for categorical variables and independent sample T test for quantitative variables., Results: A total of 60 cases and 120 controls were recruited. The logistic regression model suggested that CPITN score (OR 14.893, 95% CI 4.896, 45.301); CAL (OR 2.148, 95% CI 1.271, 3.631); calculus (OR 25.099, 95% CI 1.916, 328.771); mode of delivery (OR 0.175 95% CI 0.060, 0.514); and gingival recession (OR 0.237, 95% CI 0.078, 0.715) were significant predictors of LBW., Conclusion: Periodontal disease was found to be a significant predictor of LBW infants., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Better understanding of the different phenotypes/subgroups of non-U.S. citizen kidney transplant recipients may help the transplant community to identify strategies that improve outcomes among non-U.S. citizen kidney transplant recipients. This study aimed to cluster non-U.S. citizen kidney transplant recipients using an unsupervised machine learning approach; Methods: We conducted a consensus cluster analysis based on recipient-, donor-, and transplant- related characteristics in non-U.S. citizen kidney transplant recipients in the United States from 2010 to 2019 in the OPTN/UNOS database using recipient, donor, and transplant-related characteristics. Each cluster's key characteristics were identified using the standardized mean difference. Post-transplant outcomes were compared among the clusters; Results: Consensus cluster analysis was performed in 11,300 non-U.S. citizen kidney transplant recipients and identified two distinct clusters best representing clinical characteristics. Cluster 1 patients were notable for young age, preemptive kidney transplant or dialysis duration of less than 1 year, working income, private insurance, non-hypertensive donors, and Hispanic living donors with a low number of HLA mismatch. In contrast, cluster 2 patients were characterized by non-ECD deceased donors with KDPI <85%. Consequently, cluster 1 patients had reduced cold ischemia time, lower proportion of machine-perfused kidneys, and lower incidence of delayed graft function after kidney transplant. Cluster 2 had higher 5-year death-censored graft failure (5.2% vs. 9.8%; p < 0.001), patient death (3.4% vs. 11.4%; p < 0.001), but similar one-year acute rejection (4.7% vs. 4.9%; p = 0.63), compared to cluster 1; Conclusions: Machine learning clustering approach successfully identified two clusters among non-U.S. citizen kidney transplant recipients with distinct phenotypes that were associated with different outcomes, including allograft loss and patient survival. These findings underscore the need for individualized care for non-U.S. citizen kidney transplant recipients.

We examine the connectedness of the COVID vaccination with the economic policy uncertainty, oil, bonds, and sectoral equity markets in the US within time and frequency domain. The wavelet-based findings show the positive impact of COVID vaccination on the oil and sector indices over various frequency scales and periods. The vaccination is evidenced to lead the oil and sectoral equity markets. More specifically, we document strong connectedness of vaccinations with communication services, financials, health care, industrials, information technology (IT) and real estate equity sectors. However, weak interactions exist within the vaccination-IT-services and vaccination-utilities pairs. Moreover, the effect of vaccination on the Treasury bond index is negative, whereas the economic policy uncertainty shows an interchanging lead and lag relation with vaccination. It is further observed that the interrelation between vaccination and the corporate bond index is insignificant. Overall, the impact of vaccination on the sectoral equity markets and economic policy uncertainty is higher than on oil and corporate bond prices. The study offers several important implications for investors, government regulators, and policymakers., (© The Author(s) 2023.)

Various empirical studies have examined the nexus between financial markets, but this study focused on the comovement among prominent markets. Our study examines the interrelationship among main financial markets, i.e., stock, oil, and commodity during the recent pandemic. The interconnections among the selected markets are investigated using a battery of wavelet coherence tools and the Granger causality test. From the wavelet coherence analysis, our findings indicate strong co-movements among the VIX, oil volatility, and commodity prices during pandemic and localized in all scales and over the sample period. The dependency strength among the considered economies is noted to increase in pandemic, which implies increased short- and long-term benefits for the investors. Moreover, Our result exhibits a feedback causality between OVIX and crude oil, VIX and S&P 500, and gasoline and VIX. Interestingly, a unidirectional causality exists between VIX and crude oil, S&P 500 and crude oil, Brent and crude oil, gasoline, crude oil, and VIX and OVIX. We advocate that the findings will be helpful for portfolio managers, investors, and officials around the world., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A cross sectional analytical study was conducted from September 26 to December 28 2018 at Shifa Tameer-e-Millat University Islamabad with 111 undergraduate students aged 17-26 years as participants. The aim of the study was to establish the normative values of cervical joint positioning error (CJPE) and its association with cervical spine mechanics. Neck discomfort was measured using the neck portion of the "student specific Cornell Musculoskeletal Discomfort Questionnaire" (ssCMDQ) and CJPE was measured via cervico-cephalic relocation test using a goniometer. Non-parametric tests of significance were used because the data was not normally distributed in terms of normality testing. Normative values of CJPE were noted to be highest in flexion (9o±9o), rotation towards left (9o±6o) and right (8o±7o), extension (6o±8o), and lastly lateral flexion towards left (5o±7o) and right (5o±5o). Higher CJPE in all movements was observed among females; however, no significant statistical differences were observed (p>0.05). In terms of correlation, important trends included significantly positive correlation of neck discomfort with CJPE in extension, and of CJPE in lateral flexion towards the left with CJPE in lateral flexion towards the right and flexion (p<0.05).

Objective: Psychological well-being (PWB) is linked with health behaviors among adults, but it is unclear if childhood PWB prospectively predicts healthy adulthood biobehavioral profiles. Such evidence may identify developmental windows for establishing positive health trajectories across the lifespan. Using data spanning 30 years, we investigated whether PWB at age 11 was associated with health behaviors and body mass index (BMI) at ages 33 and 42. We hypothesized children with higher versus lower PWB would engage in healthier behaviors, have lower BMI in adulthood, and be more likely to maintain optimal levels over time., Method: Data were from 4,728 participants of the 1958 National Child Development Study. At age 11, participants wrote an essay about how they imagined their lives at age 25. Two judges rated each essay for multiple facets of PWB, which were combined into a summary score (Cronbach's α = .91). At ages 33 and 42, participants reported on cigarette smoking, physical activity, and diet; BMI was also assessed. Regression models evaluated PWB's association with adult outcomes at each follow-up, and with patterns over time., Results: Child PWB was unassociated with smoking in adulthood. However, greater child PWB was associated with healthier adult physical activity, diet, and BMI when adjusting for sex. Child PWB was associated with the likelihood of maintaining optimal BMI in adulthood, but not with maintaining healthy behaviors. Some associations were not independent of other childhood covariates., Conclusions: Early life lays the foundation for lifelong health. Childhood PWB may contribute to healthier behaviors and BMI in adulthood. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background Positive cardiometabolic health (CMH) is defined as meeting recommended levels of multiple cardiometabolic risk factors in the absence of manifest disease. Prior work finds that few individuals-particularly members of minoritized racial and ethnic groups-meet these criteria. This study investigated whether psychological assets help adolescents sustain CMH in adulthood and explored interactions by race and ethnicity. Methods and Results Participants were 3478 individuals in the National Longitudinal Study of Adolescent Health (49% female; 67% White, 15% Black, 11% Latinx, 6% other [Native American, Asian, or not specified]). In Wave 1 (1994-1995; mean age=16 years), data on 5 psychological assets (optimism, happiness, self-esteem, belongingness, and feeling loved) were used to create a composite asset index (range=0-5). In Waves 4 (2008; mean age=28 years) and 5 (2016-2018; mean age=38 years), CMH was defined using 7 clinically assessed biomarkers. Participants with healthy levels of ≥6 biomarkers at Waves 4 and 5 were classified as maintaining CMH over time. The prevalence of CMH maintenance was 12%. Having more psychological assets was associated with better health in adulthood (odds ratio [OR] linear trend , 1.12 [95% CI, 1.01-1.25]). Subgroup analyses found substantive associations only among Black participants (OR, 1.35 [95% CI, 1.00-1.82]). Additionally, there was some evidence that racial and ethnic disparities in CMH maintenance may be less pronounced among participants with more assets. Conclusions Youth with more psychological assets were more likely to experience favorable CMH patterns 2 decades later. The strongest associations were observed among Black individuals. Fostering psychological assets in adolescence may help prevent cardiovascular disease and play an underappreciated role in shaping health inequities.

Autism spectrum disorder (ASD) is defined as a neurodevelopmental disorder which results in impairments in social communications and interactions as well as repetitive behaviors. Despite current estimates showing that approximately 2.2% of children are affected in the United States, relatively little about ASD pathophysiology is known in part due to the highly heterogenous presentation of the disorder. Given the limited knowledge into the biological mechanisms governing its etiology, the diagnosis of ASD is performed exclusively based on an individual's behavior assessed by a clinician through psychometric tools. Although there is no readily available biochemical test for ASD diagnosis, multivariate statistical methods show considerable potential for effectively leveraging multiple biochemical measurements for classification and characterization purposes. In this work, markers associated with the folate dependent one-carbon metabolism and transulfuration (FOCM/TS) pathways analyzed via both Fisher Discriminant Analysis and Support Vector Machine showed strong capability to distinguish between ASD and TD cohorts. Furthermore, using Kernel Partial Least Squares regression it was possible to assess some degree of behavioral severity from metabolomic data. While the results presented need to be replicated in independent future studies, they represent a promising avenue for uncovering clinically relevant ASD biomarkers.

Background: Serum chloride derangement is common in critically ill patients requiring continuous renal replacement therapy (CRRT). We aimed to assess the association between serum chloride levels before and during CRRT with mortality., Methods: This is a retrospective cohort study of critically ill patients receiving CRRT for acute kidney injury from December 2006 through November 2015 in a tertiary referral hospital in the United States. We used logistic regression to assess serum chloride before and mean serum chloride during CRRT as predictors for 90 days mortality after CRRT initiation. The normal reference range for serum chloride was 99-108 mmol/L., Results: Of 1282 eligible patients, 25%, 50%, and 25% had hypochloremia, normochloremia, and hyperchloremia, respectively. The adjusted odds ratio for 90 days mortality in patients with hypochloremia before CRRT was 1.82 (95% CI 1.29-2.55). During CRRT, 4%, 70%, 26% of patients had mean serum chloride in the hypochloremia, normochloremia, and hyperchloremia range, respectively. The adjusted odds ratio for 90 days mortality in patients with mean serum chloride during CRRT in the hypochloremia range was 2.96 (95% CI 1.43-6.12). Hyperchloremia before and during CRRT was not associated with mortality. The greater serum chloride range during CRRT was associated with increased mortality (OR 1.29; 95% CI 1.13-1.47 per 5 mmol/L increase)., Conclusion: Hypochloremia before and during CRRT is associated with higher mortality., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Objective: Leukocyte telomere length (LTL) may be a biomarker for chronic disease susceptibility, but no work has tested this hypothesis directly. Our study investigated associations of LTL at birth with markers of adiposity growth that are linked with cardiometabolic health later in life., Methods: Participants were 375 children in Project Viva (48% female, 71% White). Body mass index (BMI) trajectories from birth to 18 years were tracked using repeated measures of BMI collected in physical examinations and via medical records, then used to predict age (months) and magnitude (kg/m 2 ) of BMI peak and rebound. LTL was measured from cord blood via duplex quantitative PCR. A binary variable indicating LTL shorter than the reference population average was the primary exposure., Results: LTL was unrelated to BMI at peak or rebound, but associations were apparent with the timing of BMI growth milestones. Short LTL was related to a later age of peak for females (β = 0.99, 95% CI = 0.16, 1.82; p sex interaction  = 0.015) and an earlier age of rebound for both males and females (β combined  = -5.26, 95% CI = -9.44, -1.08)., Conclusion: LTL at birth may be an early biomarker of altered adiposity growth. Newborn telomere biology may shed new insight into the developmental origins of health and disease., (© 2022 World Obesity Federation.)

Pornography addiction is an area of increasing concern, particularly due to the ubiquitous nature of pornographic material on the Internet. Even so, there is no formal Diagnostic and Statistical Manual of Mental Disorders (DSM-5) inclusion of compulsive pornography use as a behavioral addiction. Although the psychosocial impacts of pornography addiction have been studied, the risk of direct skin injuries and behavioral changes brought about by excessive pornography usage remain to be seen. Adult males constitute the majority of cases of engaging in risky and violent sexual behaviors with an unclear association with pornography consumption. Adult females may be likely to copy pubic hair trimming patterns analogous to those seen in pornographic content, even though attitudes towards labiaplasty are unclear. Finally, adolescents regularly exposed to pornography have been found to replicate sexual activity seen in pornographic material and have earlier sexual activity. In the literature evaluated, an association between pornographic material and direct cutaneous disease remains a major area of further research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Rasul et al.)

Introduction: We aimed to assess the association between serum potassium and mortality in patients receiving continuous renal replacement therapy (CRRT)., Methods: We studied 1279 acute kidney injury patients receiving CRRT in a tertiary referral hospital in the United States. We used logistic regression to assess the association of serum potassium before CRRT and mean serum potassium during CRRT with 90-day mortality after CRRT initiation, using serum potassium 4.0-4.4 mmol/L as reference group., Results: Before CRRT, there was a U-shaped association between serum potassium and 90-day mortality. There was a significant increase in mortality when serum potassium before CRRT was ≤3.4 and ≥4.5 mmol/L. During CRRT, progressively increased mortality was noted when mean serum potassium was ≥4.5 mmol/L. The odds ratio of 90-day mortality was significantly higher when mean serum potassium was ≥4.5 mmol/L., Conclusion: Hypokalemia and hyperkalemia before CRRT and hyperkalemia during CRRT predicts 90-day mortality., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

This systematic review synthesizes research published from January 2010-July 2022 on the social determinants of ideal cardiovascular health (CVH) carried out around the world and compares trends in high-income countries (HICs) to those in low- and middle-income countries (LMICs). 41 studies met inclusion criteria (n = 28 HICs, n = 13 LMICs). Most were from the United States (n = 22) and cross-sectional (n = 33), and nearly all evaluated associations among adults. Among studies conducted in LMICs, nearly all were from middle-income countries and only one was carried out in low-income country. Education (n = 24) and income/wealth (n = 17) were the most frequently examined social determinants in both HICs and LMICs. Although most studies assessed ideal CVH using reliable and valid methods (n = 24), only 7 used criteria pre-defined by the American Heart Association to characterize ideal levels of each CVH metric. Despite heterogeneity in how outcome measures were derived and analyzed, consistent associations were evident between multiple markers of higher social status (i.e. greater education, income/wealth, socioeconomic status, racial/ethnic majority status) and greater levels of ideal CVH across both country contexts. Gaps in the literature include evidence from LMICs and HICs other than the United States, longitudinal research, and investigations of a wider array of social determinants beyond education and income/wealth., (Copyright © 2022. Published by Elsevier Inc.)

The immunomodulatory capacity of the human mesenchymal stromal cell (MSC) secretome has been a critical driver for the development of cell-free MSC products, such as conditioned medium (CM), for regenerative medicine applications. This is particularly true as cell-free MSC products present several advantages over direct autologous or allogeneic MSC delivery with respect to safety, manufacturability, and defined potency. Recently, significant effort has been placed into creating novel MSC CM formulations with an immunomodulatory capacity tailored for specific regenerative contexts. For instance, the immunoregulatory nature of MSC CM has previously been tuned through a number of cytokine-priming strategies. Herein, we propose an alternate method to tailor the immunomodulatory "phenotype" of cytokine-primed MSC CM through coupling with the pharmacological agent, suramin. Suramin interferes with the signaling of purines including extracellular adenosine triphosphate (ATP), which plays a critical role in the activation of the innate immune system after injury. Toward this end, human THP-1-derived macrophages were activated to a proinflammatory phenotype and treated with (1) unprimed/native MSC CM, (2) interferon-γ/tumor necrosis factor α-primed MSC CM (primed CM), (3) suramin alone, or (4) primed MSC CM and suramin (primed CM/suramin). Markers of key macrophage functions-cytokine secretion, autophagy, oxidative stress modulation, and activation/migration-were assessed. Consistent with previous literature, primed CM elevated macrophage secretion of several proinflammatory and pleiotropic cytokines relative to native CM; whereas addition of suramin imparted consistent shifts in terms of TNFα (↓), interleukin-10 (↓), and hepatocyte growth factor (↑) irrespective of CM. In addition, both primed CM and suramin, individually and combined, increased reactive oxygen species production relative to native CM, and addition of suramin to primed CM shifted levels of CX3CL1, a factor involved in ATP-associated macrophage regulation. Varimax rotation assessment of the secreted cytokine profiles confirmed that primed CM/suramin resulted in a THP-1 phenotypic shift away from the lipopolysaccharide-activated proinflammatory state that was distinct from that of primed CM or native CM alone. This altered primed CM/suramin-associated phenotype may prove beneficial for healing in certain regenerative contexts. These results may inform future work coupling antipurinergic treatments with MSC-derived therapies in regenerative medicine applications.

We report microwave synthesis of seven unique pyrimidine anchored derivatives ( 1 - 7 ) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1 - 7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1 - 7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC 50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively. Molecular docking was performed for derivatives ( 1 - 7 ) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1 - 7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3 , all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella ( P. dentalis , P. enoeca , P. oris , P. meloninogenica ), Bifidobacterium bifidum , and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.

Objectives: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC., Methods: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed., Results: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable., Conclusion: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations., Prospero Registration Number: CRD42021237127., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to develop and validate an automated machine learning (autoML) prediction model for cardiac surgery-associated acute kidney injury (CSA-AKI)., Methods: Using 69 preoperative variables, we developed several models to predict post-operative AKI in adult patients undergoing cardiac surgery. Models included autoML and non-autoML types, including decision tree (DT), random forest (RF), extreme gradient boosting (XGBoost), and artificial neural network (ANN), as well as a logistic regression prediction model. We then compared model performance using area under the receiver operating characteristic curve (AUROC) and assessed model calibration using Brier score on the independent testing dataset., Results: The incidence of CSA-AKI was 36%. Stacked ensemble autoML had the highest predictive performance among autoML models, and was chosen for comparison with other non-autoML and multivariable logistic regression models. The autoML had the highest AUROC (0.79), followed by RF (0.78), XGBoost (0.77), multivariable logistic regression (0.77), ANN (0.75), and DT (0.64). The autoML had comparable AUROC with RF and outperformed the other models. The autoML was well-calibrated. The Brier score for autoML, RF, DT, XGBoost, ANN, and multivariable logistic regression was 0.18, 0.18, 0.21, 0.19, 0.19, and 0.18, respectively. We applied SHAP and LIME algorithms to our autoML prediction model to extract an explanation of the variables that drive patient-specific predictions of CSA-AKI., Conclusion: We were able to present a preoperative autoML prediction model for CSA-AKI that provided high predictive performance that was comparable to RF and superior to other ML and multivariable logistic regression models. The novel approaches of the proposed explainable preoperative autoML prediction model for CSA-AKI may guide clinicians in advancing individualized medicine plans for patients under cardiac surgery.

Hypernatremia (serum sodium>160 meq/L) present with diverse neurological manifestations, ranging from flaccid paralysis to impaired cognition, encephalopathy, and even deep coma. Osmotic demyelination refers to changes in brain cells because of an acute change in plasma osmolality. It is further divided into two types, i.e., central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM). Patients with EPM, besides spasticity, may also present with other movement disorders such as catatonia, parkinsonism, and dystonia. We present a case of a postpartum woman bought to the emergency department by her relatives in an unconscious state. In view of poor sensorium (Glasgow coma scale < 7), she was intubated and received mechanical ventilatory support. On admission, computed tomography ofthebrain was normal, and the patient was transferred to the intensive care unit (ICU) for further management. The preliminary work-up in the ICU showed hypernatremia (serum sodium of 182 mEq/L) with hyper-osmolality (359 mOsm/kgH 2 O). She was managed as per the ICU protocol for hypernatremia. During her ICU stay, her sensorium improved, but she developed flaccid paralysis and was quadriplegic. Thus, a tracheostomy was performed, and she was weaned from the ventilator. After ventilator weaning, she was transferred to the ward for further rehabilitation. During rehabilitation, the patient was able to sit and takefoodorally.To date, only a few cases are reported in postpartum women with acute severe hypernatremia caused by high-grade fever and loss of body fluids leading to extra-pontine demyelination and flaccid paralysis. This case highlightsthat prompt recognition and appropriate intervention can improve the outcomes in these patients., (© 2022 Choudhary, Qureshi, Arora, Kothari, Tiwari, Bhatia, licensee HBKU Press.)

Objective: Compliance with perioperative antibiotic prophylaxis is crucial for preventing surgical site infection. Anesthesiologists can play a significant role in reducing surgical site infections by following clinical practice guidelines for antibiotic prophylaxis and redosing during surgery. A quality assurance initiative was implemented at a tertiary hospital with the goal of improving cefazolin perioperative antibiotic compliance., Design: This was a retrospective observational study., Setting: Main operating room of a tertiary care teaching hospital in New York, USA. Our main operating room includes 22 operating rooms that incorporates surgeries from general surgery, vascular surgery, neurology, gynecology, urology, orthopedics, ear, nose and throat (ENT) etc., Participants: All cases in the main operating room from March 1, 2018 to March 31, 2021 that received first dose of Cefazolin and in which the duration of surgery was more than 4 hrs., Intervention: A multifaceted intervention was initiated to address low compliance with cefazolin redosing. Multifaceted interventions included the development of a perioperative antibiotic guide for anesthesia providers, automated reminders in anesthesia electronic medical records, grand rounds education, survey and email communications, and regular feedback reports to the anesthesia department., Main Outcome Measures: Cefazolin perioperative redose compliance rate., Results: Rates of redose compliance were examined in three time periods: preintervention, intervention and postintervention. Cefazolin redosing compliance was 58% in the preintervention period and 90% in the postintervention period. There was a significant positive change in the trend of compliance during the intervention period, indicating that the odds of compliance increased by 13% per month in the intervention period compared to the preintervention period (odds ratio = 1.13, P < 0.001). Redose compliance improvements were sustained a year after the postintervention period (an average of 91%). Surgical site infection rates for colon, coronary artery bypass graft and hip surgeries did not show any significant trend during these time periods., Conclusion: Multifaceted interventions led to significant and sustained improvements in cefazolin redosing compliance in the main operating room of a tertiary hospital., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Silver Phosphate, Ag3PO4, being a highly capable clinical molecule, an ultrasonic method was employed to synthesize the M-Ag3PO4, (M = Se, Ag, Ta) nanoparticles which were evaluated for antibacterial and cytotoxicity activities post-characterization. Escherichia coli and Staphylococcus aureus were used for antibacterial testing and the effects of sonication on bacterial growth with sub-MIC values of M-Ag3PO4 nanoparticles were examined. The effect of M-Ag3PO4 nanoparticles on human colorectal carcinoma cells (HCT-116) and human cervical carcinoma cells (HeLa cells) was examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and DAPI (4′,6-diamidino-2-phenylindole) staining. Additionally, we analyzed the effect of nanoparticles on normal and non-cancerous human embryonic kidney cells (HEK-293). Ag-Ag3PO4 exhibited enhanced antibacterial activity followed by Ta-Ag3PO4, Ag3PO4, and Se-Ag3PO4 nanoparticles against E. coli. Whereas the order of antibacterial activity against Staphylococcus aureus was Ag3PO4 > Ag-Ag3PO4 > Ta-Ag3PO4 > Se-Ag3PO4, respectively. Percentage inhibition of E. coli was 98.27, 74.38, 100, and 94.2%, while percentage inhibition of S. aureus was 25.53, 80.28, 99.36, and 20.22% after treatment with Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4, respectively. The MTT assay shows a significant decline in the cell viability after treating with M-Ag3PO4 nanoparticles. The IC50 values for Ag3PO4, Se-Ag3PO4, Ag-Ag3PO4, and Ta-Ag3PO4 on HCT-116 were 39.44, 28.33, 60.24, 58.34 µg/mL; whereas for HeLa cells, they were 65.25, 61.27, 75.52, 72.82 µg/mL, respectively. M-Ag3PO4 nanoparticles did not inhibit HEK-293 cells. Apoptotic assay revealed that the numbers of DAPI stained cells were significantly lower in the M-Ag3PO4-treated cells versus control.

Background: Heart disease is the fourth leading cause of death for young adults aged 18-34 in the United States. Recent research suggests that adverse childhood experiences (ACEs) may shape cardiovascular health and its proximate antecedents. In the current study, we draw on a contemporary, national sample to examine the association between ACEs and cardiovascular health among young adults in the United States, as well as potential mediating pathways. Methods: The present study uses data from the 2019 Behavioral Risk Factor Surveillance System (BRFSS) to examine associations between ACEs and cardiovascular risk, as well as the role of cumulative disadvantage and poor mental health in these associations. Results: Findings indicate that young adults who have experienced a greater number of ACEs have a higher likelihood of having moderate to high cardiovascular risk compared to those who have zero or few reported ACEs. Moreover, both poor mental health and cumulative disadvantage explain a significant proportion of this association. Conclusions: The present findings suggest that young adulthood is an appropriate age for deploying prevention efforts related to cardiovascular risk, particularly for young adults reporting high levels of ACEs.

Background In downtown Kansas City, patients who face homelessness or unstable housing situations may have been negatively affected by the shutdown of Sojourner Health Clinic (SOJO), a free student-run clinic that provides primary care predominantly to these patients. Research shows that blood pressure (BP) increases within weeks or months of interruption of antihypertensive therapy, especially in patients with advanced age and polypharmacy. Therefore, this study will examine how patients' blood pressure changed after the closure of Sojourner Health Clinic. Methods The study population consists of Sojourner Health Clinic patients who were seen both before March 2020 (shutdown) and during/after July 2020 (clinic reopening). Participants are selected at random. No additional data is collected outside of routine treatment for this institutional review board (IRB)-exempt project. A study coordinator reviews charts via Sojourner electronic medical record (EMR) and collects the latest BP available before March 2020 and the first BP available during/after July 2020. No identifying information is collected. The mean systolic pressures, mean diastolic pressures, and mean arterial pressures (MAP) are compared via paired t-test for statistical significance. Results There was a statistically significant decrease in patients' MAP and diastolic BP after the closure of the clinic. However, there was not a statistically significant change found in patients' systolic BP. The clinical significance of these results is limited by the minimal magnitude of change. Conclusions These findings run counter to our expectations since we believed that the closure of Sojourner Health Clinic would correlate with worsened markers of health, such as blood pressure control. It may be possible that the sampled patients turned to other sources for health maintenance and antihypertensive therapy during clinic closure. Future studies could explore these possibilities., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Qureshi et al.)

Introduction Radiation-emitting devices are commonplace in the hospital with their ability to produce imaging for diagnoses, However, they hold a risk for device operators due to radiation exposure. Hospital systems have programs where physicians exposed to radiation are required to wear dosimeters to help record total radiation over time. Dosimetry readings over standardized recommendations can lead to hospital image issues and disciplinary action for physicians. This study aimed to discover the true values recorded on dosimeters with radiation exposure and discuss effective ways to encourage compliance with dosimeter usage. Methodology The study was completed over a course of 12 months with physicians from three different hospitals. Selection criteria included physicians considered to be "radiation workers" including those who operate x-ray machines, fluoroscopy units, unsealed and sealed isotopes, or those exposed to other sources of gamma or high-energy beta radiation. Two Plan-Do-Study-Act (PDSA) cycles were implemented. The first cycle was the first six months of the study and the second cycle was the second six months of the study. The first PDSA cycle had planned dosimeter reading check-ins every month. After this cycle ended, physicians were sent a survey anonymously asking if they had ever intentionally left behind their dosimeter. In the second PDSA cycle, a planned policy change was put into action where penalties for physicians who went over the recommended dosage were stopped. A monthly educational meeting where a discussion on the risks of radiation as well as protective mechanisms was implemented instead. The same monthly check-ins for dosimeter reading monitoring were employed again with the same survey regarding dosimeter adherence and usage being sent out at the end of the second cycle. Run charts were created to determine whether the policy change showed statistically significant differences in dosimetry readings. Results Protocol changes led to statistically significant (p<0.05) differences in radiation exposure recorded throughout the hospital systems. The primary PDSA cycle readings showed that hospital systems one (n=118), two (n=71), and three (n=32) had readings of 3.90 mSv, 2.55 mSv, and 2.02 mSv, respectively, which were all under the annual recommended dose limit of 10 mSv maximum per six months. However, an average of 94.4% (n=221) of physicians across all hospitals admitted to not using the dosimeter. In the second PDSA cycle after the policy change, the radiation doses were higher with an increase in the average cumulative dose at hospital system one of 255%, 328% at system two, and 323% at system three. Hospital systems one and two were both over the yearly limit of 20.0 mSv (7.70 mSv over for system one and 1.86 mSv over for system two) while system three remained under. The number of physicians who stated they always used the dosimeter during the second PDSA cycle increased to 83.9% in-hospital system one, 90.2% in-hospital system two, and 93.8% in-hospital system three. Conclusion Creating a culture of safety is critical for physician compliance. A comfortable work environment without unreasonable consequences creates an environment where physicians can focus on their health and safety while also doing what is in the workplace's best interest. This culture can best be made with more collaboration between administrative staff and workers to create a trustworthy experience in hospital systems., Competing Interests: I would like to disclose that an author on this project, Fahad Qureshi, has worked with Dr. Raza Ali Khan and Dr. Serkan Surucu, who we have invited as potential reviewers for our paper. Both physicians have been informed and are aware of the need to consider any personal conflicts of interest before agreeing to review and the importance of declaring any conflicts of interest before submitting their review if they should decide to do so., (Copyright © 2022, Qureshi et al.)

Childhood adversity is linked to poor cardiometabolic outcomes, but less is known about positive childhood factors. Using data from 4,007 members of the 1958 British Birth Cohort, we investigated whether children with greater psychological well-being had lower adulthood cardiometabolic risk. At age 11, participants wrote essays about their future. Two judges rated each essay for nine psychological well-being items (Finn's r = .82-.91), which were combined into a standardized overall score (Cronbach's α = .91). When participants reached age 45, nurses assessed their blood pressure, heart rate, lipids, glycosylated hemoglobin, fibrinogen, and C-reactive protein, which were standardized and summed for total cardiometabolic risk. Regressions indicated that children with greater psychological well-being had lower cardiometabolic risk ( b = -0.14, 95% confidence interval [CI] = [-0.28, -0.006]): specifically, healthier total cholesterol ( b = -0.04, 95% CI = [-0.07, -0.003]) and triglycerides ( b = -0.06, 95% CI = [-0.09, -0.02]). Childhood psychological well-being may promote adulthood cardiometabolic health.

Background: There is limited evidence on the association of serum phosphate with mortality in patients receiving continuous renal replacement therapy (CRRT)., Objective: To assess the association of serum phosphate with mortality in critically ill patients requiring CRRT for acute kidney injury (AKI)., Design: A cohort study., Setting: A tertiary referral hospital in the United States., Patients: Acute kidney injury patients receiving CRRT from 2006 through 2015 in intensive care units., Measurements: (1) Serum phosphate before CRRT and (2) mean serum phosphate during CRRT were categorized into 3 groups; ≤2.4 (hypophosphatemia), 2.5 to 4.5 (normal serum phosphate group), and ≥4.6 (hyperphosphatemia) mg/dL., Methods: Multivariable logistic regression was used to assess the association between serum phosphate and 90-day mortality., Results: A total of 1108 patients were included in this study. Of these, 55% died within 90 days after CRRT initiation. Before CRRT, 3%, 30%, and 66% had hypophosphatemia, normophosphatemia, and hyperphosphatemia, respectively. Before CRRT, both hypophosphatemia and hyperphosphatemia were significantly associated with higher 90-day mortality with the adjusted odds ratio (OR) of 2.22 (95% confidence interval [CI]: [1.03, 4.78]) and 1.62 (95% CI: [1.21, 2.18]), respectively. During CRRT, 3%, 85%, and 12% had mean serum phosphate in hypophosphatemia, normophosphatemia, and hyperphosphatemia range. During CRRT, hyperphosphatemia was significantly associated with higher 90-day mortality with adjusted OR of 2.22 (95% CI: [1.45, 3.38])., Limitations: Single center, observational design, lack of information regarding causes of serum phosphate derangement., Conclusion: Most CRRT patients had hyperphosphatemia before CRRT initiation but maintain normal serum phosphate during CRRT. Before CRRT, hypo- and hyperphosphatemia, and during CRRT, hyperphosphatemia predicted higher mortality., Trial Registration: Not registered., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Competing Interests: There are no conflicts of interest.

Aging populations often experience difficulties hearing. This phenomenon, known as age-related hearing loss, is associated with decreases in hearing sensitivity and pathophysiological changes in the central auditory system, including the primary auditory cortex (AI). To better understand changes in the central auditory system, this study is designed to compare the receptive fields of AI neurons of young and old C57 mice in frequency, amplitude, and temporal domains by using random-delivery (various interval) of multi-frequency gamma-shaped tone pips and a novel data processing approach known as the intensity-stacked spectrotemporal receptive field (iSTRF). We show that the fundamental changes in the response properties of AI neurons in old mice were in line with the literature. Compared to young mice, AI neurons in old mice tuned to lower frequency and higher amplitude of tones with broader frequency tuning, shorter dB (dynamic) range, longer response duration, as well as a higher firing rate. We further compared the entire iSTRF and core iSTRF (above 50% maximal firing rate) between young and old mice; the core iSTRF represented the AI neuronal responses to sound that fall into the central frequency and amplitude ranges from the auditory periphery. It is remarkable that the difference was significant in the entire iSTRF while little difference was observed in the core iSTRFs between young and old mice. However, the lower best frequency and higher best amplitude were obvious in both iSTRFs that were mostly determined by the deficits in the inner ears of old mice. In the frequency domain, the tuning quality factor of entire iSTRFs was significantly greater in old mice, while that of core iSTRFs was not compared to young mice. In the amplitude domain, significantly shorter dB range in old mice were observed in the entire iSTRF, but not in the core iSTRF. In the temporal domain, the response duration of old AI neurons was significantly longer in entire iSTRFs, but not in core iSTRFs, when compared to young AI neurons. Furthermore, the average firing rate of old AI neurons was significantly higher in entire iSTRF, but not in core iSTRF. It is also interesting that the ratio of the firing rate to background firing rate (signal-noise ratio) were similar between young and old AI neurons. Our data suggests that age-related hearing loss has relatively less impact on auditory information processing when sounds fall into the optimal frequency and amplitude ranges of given AI neurons., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests. All authors have seen and approved the final version of the manuscript being submitted. They warrant that the article is the authors' original work, hasn't received prior publication and isn't under consideration for publication elsewhere., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Prior work indicates a robust relationship between coffee consumption and lower depression risk, yet no research has examined links with psychological well-being (e.g., happiness, optimism). This study tested whether coffee intake is prospectively associated with greater psychological well-being over time. Secondarily, associations in the reverse direction were also examined to determine whether initial levels of psychological well-being were related to subsequent coffee consumption., Methods: Among women in the Nurses' Health Study, coffee consumption was examined in 1990 and 2002 in relation to sustained levels of happiness reported across multiple assessments from 1992-2000 (N = 44,449) and sustained levels of optimism assessed from 2004-2012 (N = 36,729). Associations were tested using generalized estimating equations with a Poisson distribution adjusted for various relevant covariates. Bidirectional relationships were evaluated in secondary analyses of baseline happiness (1992) and optimism (2004) with sustained moderate coffee consumption across multiple assessments through 2010., Results: Compared to minimal coffee consumption levels (<1 cup/day), moderate consumption (1-3 cups/day) was unrelated to happiness, whereas heavy consumption (≥4 cups/day) was associated with a 3% lower likelihood of sustained happiness (relative risk, RR = 0.97, 95% CI = 0.95-0.99). Only moderate coffee consumption was weakly associated with a greater likelihood of sustained optimism (RR1-3cups/day = 1.03, 95% CI = 1.00-1.06). Secondary analyses showed high levels of optimism but not happiness levels were modestly associated with increased likelihood of sustained moderate coffee intake (RRoptimism = 1.06, 95% CI = 1.02-1.10; RRhappiness = 1.01, 95% CI = 0.99-1.04)., Conclusions: Associations between psychological well-being and coffee consumption over up to two decades were largely null or weak. Although coffee consumption may protect individuals against depression over time, it may have limited impact on facets of psychological well-being., Competing Interests: The authors declare that they have no conflicts of interest.