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Background: Alcohol use remains an important contributor to morbidity and mortality. There is a long-time gap between the onset of alcohol use and first contact for care. Poor referral systems and reduced awareness contribute to such delays. Yet few studies analyzed pathways to care exclusively in alcohol-dependent patients. Aims: The aim of this study was to understand the pathways traversed by alcohol-dependent patients before their access to psychiatric services and their association with sociodemographic and clinical characteristics. Methods: A cross-sectional study design was employed. All alcohol-dependent patients attending psychiatric outpatient department setting were recruited. Questionnaires including sociodemographic details, the Short Alcohol Dependence Data Questionnaire, and the World Health Organization encounter forms were used. Appropriate statistical tests were done using SPSS 20. Results: A total of 99 patients were inducted into the study. 44.44% consulted psychiatric services directly. There was a mean time lag of 15 years between the onset of alcohol use and first contact. There was a significant association between sociodemographic characteristics and the pathway chosen. Higher severity of dependence and longer duration of alcohol use were associated with patients visiting psychiatric services indirectly. The main source of referral was family members for the first contact and medical practitioner for a referral to psychiatric services. Conclusion: Understanding the pathway traversed is critical to planning effective interventions in alcohol-dependent patients. Sociodemographic variables seem to be important predictors for the pathway traversed. Although the referral system by medical practitioners is satisfactory, there is a huge gap in accessibility to psychiatric services. There is a need for community awareness programs to prevent time lag.

Coronary artery calcium (CAC) is the measure of subclinical coronary artery atherosclerosis most strongly associated with atherosclerotic cardiovascular disease (ASCVD) risk. However, CAC is rarely reported in the inpatient setting to guide chest pain management. We present a case of very high CAC in a 64-year-old woman with hypertension, type 2 diabetes, and hyperlipidemia presenting with dyspnea. Initial electrocardiogram (ECG) demonstrated normal conduction with a heart rate of 76 beats/min, but new T-wave inversions in V1–V4 and a high-sensitivity troponin-I (hsTnI) value of 6 ng/L (normal

This is a report on an inaugural medical student elective, Microbiomes Matter: The Path to Regenerative Systems of Farm, Food, and Health, from the perspective of the student participants. Recognizing food as medicine is gaining support across many settings. However, little is known about how medical schools engage in this holistic approach. Integrating food systems and the connections to soil and human health through microbiomes into medical education represents a transformative shift towards more holistic healthcare practices. We describe the course content and impact of a medical school elective in food systems. This elective employed a systems lens and planetary health perspective to explore the impact of climatic factors and environmental degradation on farms, nutrition, and non-communicable lifestyle diseases. Through the two-week course, medical students gained insights into sustainable food systems, supply chains, and the importance of regenerative agriculture. The course also provided a comprehensive overview of the gut microbiome, nutrition, technologies, and the economics of food systems, including their impact on lifestyle diseases. By fostering a systems-oriented mindset, this elective better equips medical students to address the complex challenges of human and planetary health and promote regenerative, sustainable, culturally sensitive, and robust systems of farm, food, and health.

Abstract Genetic and neuropathological evidence strongly implicates aberrant forms of α-synuclein in neurodegeneration. Antibodies specific for α-synuclein phosphorylated at serine 129 (pS129) are selective for the pathological protein aggregates that are characteristic of Parkinson’s disease (PD) and other synucleinopathies, such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although the etiology of most synucleinopathies remains uncertain, a large body of evidence points to mitochondrial dysfunction. The recent development of animal models based on intracranial injection of α-synuclein pre-formed fibrils (PFFs) has provided a valuable experimental system in which to study the spread and neurotoxicity of α-synuclein aggregates, yet the effects of PFF-induced protein aggregates on mitochondrial function and dynamics have not been rigorously examined in vivo. To help fill this knowledge gap, we injected the striatum of mice unilaterally with well-characterized small length (

Introduction: Alcohol use disorder has a chronic relapsing course. Various biological, psychological, environmental, and psychosocial factors play a major role in maintaining abstinence and determining relapse in patients. The COVID-19 pandemic has caused significant changes in every person's life. It is important to assess how this situation has determined alcohol use in the patients who had utilized deaddiction services in the past. Aim: The aim of this study is to assess the pattern of alcohol use, perceived stress, and quality of life (QOL) during COVID-19 in patients who had utilized deaddiction services for alcohol use disorder in the preceding 1 year. Materials and Methods: A cross-sectional design was employed in the study. After obtaining consent, telephonic interviewing of patients who had utilized deaddiction services during January–December 2019 was done, and questionnaires including sociodemographic details, Severity of Alcohol Dependence Questionnaire, Brief Substance Craving Scale, Perceived Stress Scale-10, and WHOQOL-BREF scale were administered to assess the pattern of alcohol use, stress levels, and QOL. Comparisons were carried out on different variables using SPSS version 20. Results: A total of 122 patients were inducted into the study. About 70.5% of the relapsed individuals belonged to joint families. There was a significant association between the poor QOL and relapse status of the individuals. High levels of stress were reported among the individuals who have relapsed compared to nonrelapsed individuals. Conclusion: High rates of relapse and higher stress levels were found in our study. This study has helped us to understand the pattern of alcohol use in individuals during this pandemic. It is important to address the factors contributing to relapse in individuals so as to focus on developing and implementing feasible and accessible interventions to help the individuals.

Introduction: Rich neurovascular supply in the anterior mandible necessitates a preoperative radiological assessment of the lingual foramina/canal where cone beam computed tomography (CBCT) could produce promising results. Aim: To assess the prevalence of lingual foramina and canal in mandible and variations in their anatomy in a hospital-based population in Chennai. Methodology: Sagittal sections of the anterior mandible from CBCT images of 140 patients were evaluated for number, location of the lingual foramen, length of the lingual canal, a distance of lingual foramen from the alveolar crest and inferior border of the mandible, and thickness of the lingual cortex. Results: A total of 166 lingual foramina-canals were identified in 140 individuals; 82.1% presented with one, 15.1% with two, and 2.1% with three lingual foramina canals. The majority of foramina (79.51%) were located above the genial tubercles. The mean lengths of the superior, middle, and inferior canals were 5.45 ± 1.34, 5.00 ± 1.73, and 3.92 ± 1.10 mm, respectively. The mean thickness of the lingual cortex was 2.35 ± 0.55 mm. The distance from the inferior lingual foramina to the alveolar crest was significantly greater in males (P = 0.001). Conclusion: Anatomical characteristics of lingual foramen-canal varied significantly across the total sample.

Introduction: There is a modest relationship between speech perception skills and perceived hearing handicap in individuals with hearing loss. In this study, an attempt is made at linking psychoacoustic results and speech perception skills to understand the subjective handicap and quality of life. Objective: To investigate how speech perception in noise (signal to noise ratio-50), difference limen frequency, temporal modulation transfer function, hearing handicap inventory for adults, and quality of life in auditory neuropathy spectrum disorder differs from sensorineural hearing loss. Further we attempt to discern attributed factors of hearing handicap in auditory neuropathy spectrum disorder and sensorineural hearing loss. Methods: A cross-sectional study with comparative and correlational research designs were utilized. Eighty-four participants were grouped into sensorineural hearing loss (n = 49), and auditory neuropathy spectrum disorder (n = 35) was sub-grouped into mild, moderately severe, and severe. We evaluated signal to noise ratio-50, difference limen frequency, and temporal modulation transfer function. In addition, hearing handicap inventory for adults, and quality of life questionnaires were administered. Results: Mild auditory neuropathy spectrum disorder showed impairment in speech perception and discriminating frequency, which were similar to the severe sensory neural hearing loss. Temporal resolution impairment in auditory neuropathy spectrum disorder mild was significantly higher than in each sub-groups of sensorineural hearing loss. The severity of the hearing handicap in was similar to severe sensorineural hearing loss, quality of life was equally affected in sensorineural hearing loss and auditory neuropathy spectrum disorder. In sensorineural hearing loss, signal to noise ratio-50 was positively related, and quality of life was negatively related to hearing handicap. In auditory neuropathy spectrum disorder, no contributory factors were related to hearing handicap. Conclusion: Mild auditory neural pathology demonstrates impairment in speech recognition and psychoacoustic skills similar to severe cochlear pathology. In sensorineural hearing loss, hearing handicap is predicted from quality of life and speech perception, but none of the contributory factors predicted hearing handicap in auditory neuropathy spectrum disorder.

Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue sarcoma. There are two main subtypes of RMS, alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma. ARMS typically encompasses fusion‐positive rhabdomyosarcoma, which expresses either PAX3‐FOXO1 or PAX7‐FOXO1 fusion proteins. There are no targeted therapies for ARMS; however, recent studies have begun to illustrate the cooperation between epigenetic proteins and the PAX3‐FOXO1 fusion, indicating that epigenetic proteins may serve as targets in ARMS. Here, we investigate the contribution of BMI1, given the established role of this epigenetic regulator in sustaining aggression in cancer. We determined that BMI1 is expressed across ARMS tumors, patient‐derived xenografts, and cell lines. We depleted BMI1 using RNAi and inhibitors (PTC‐209 and PTC‐028) and found that this leads to a decrease in cell growth/increase in apoptosis in vitro, and delays tumor growth in vivo. Our data suggest that BMI1 inhibition activates the Hippo pathway via phosphorylation of LATS1/2 and subsequent reduction in YAP levels and YAP/TAZ target genes. These results identify BMI1 as a potential therapeutic vulnerability in ARMS and warrant further investigation of BMI1 in ARMS and other sarcomas.

Background: Continuous surveillance helps people with diabetes live better lives. A wide range of technologies, including the Internet of Things (IoT), modern communications, and artificial intelligence (AI), can assist in lowering the expense of health services. Due to numerous communication systems, it is now possible to provide customized and distant healthcare. Main problem: Healthcare data grows daily, making storage and processing challenging. We provide intelligent healthcare structures for smart e-health apps to solve the aforesaid problem. The 5G network must offer advanced healthcare services to meet important requirements like large bandwidth and excellent energy efficacy. Methodology: This research suggested an intelligent system for diabetic patient tracking based on machine learning (ML). The architectural components comprised smartphones, sensors, and smart devices, to gather body dimensions. Then, the preprocessed data is normalized using the normalization procedure. To extract features, we use linear discriminant analysis (LDA). To establish a diagnosis, the intelligent system conducted data classification utilizing the suggested advanced-spatial-vector-based Random Forest (ASV-RF) in conjunction with particle swarm optimization (PSO). Results: Compared to other techniques, the simulation’s outcomes demonstrate that the suggested approach offers greater accuracy.

Background: High intra- and interobserver variability in the follicular assessment using two-dimensional (2D) ultrasound (US) is still a concern. To solve this issue, we have developed a novel software solution, which automatically provides follicles' count and their diameters using 2D US images obtained by a manual sweep of an ovary. The primary objective of this study was to compare the result of the automated solution with a manual 2D US-based assessment. Methods: In the first phase, multiple follicular US sweeps were collected from 54 subjects; these sweeps were used to develop the software. In the second phase, data from 10 subjects were collected for validation of the developed solution. During each phase, for follicles ≥5 mm, their count and diameters were recorded by the sonologist using 2D US. Results: For the total follicle count, a high correlation (0.787) was observed between the solution and manual assessment. The 95% limits of agreement between the two methods were in the range of 4.232 to −4.258. The two methods had an excellent correlation (0.817) for the measurement of mean follicular diameter. However, the solution had a tendency to underestimate the mean diameter by an average of 1.725 mm (±2.16 mm). The limits of agreement between the two methods for mean diameter measurement were from 2.508 to −5.960 mm. Conclusion: This study validates the feasibility of our solution for automatic assessment of follicle count and diameter with accuracy comparable to the 2D US-based manual assessment. We further observed that the solution's performance is better than known intra- and interobserver variability of the manual assessment. We recommend further validation of the solution to confirm these initial results and potential time gain with an automated assessment.

Summary: In-situ resource utilization (ISRU) to refuel rockets on Mars will become critical in the future. The current effort presents a thorough feasibility analysis of a scalable, Matlab-based, integrated ISRU framework from the standpoint of the second law of thermodynamics. The ISRU model is based on existing technology that can utilize Martian resources (regolith and atmosphere) to produce rocket propellants. Model simulations show that the system analysis is theoretically consistent with a positive entropy generation, and the achievable mass flow rates of liquid methane and liquid oxygen can potentially meet the 16-month rocket refueling deadline (on Mars) as desired by the National Aeronautics and Space Administration. However, the model is sensitive to liquid oxygen storage temperatures, and lower temperatures are necessary to minimize compressor work. This proof-of-concept model can open avenues for further experimental evaluation of the system to achieve a higher technology readiness level.

Multicomponent catalysts can be designed to synergistically combine reaction intermediates at interfacial active sites, but restructuring makes systematic control and understanding of such dynamics challenging. We here unveil how reducibility and mobility of indium oxide species in Ru-based catalysts crucially control the direct, selective conversion of CO2 to ethanol. When uncontrolled, reduced indium oxide species occupy the Ru surface, leading to deactivation. With the addition of steam as a mild oxidant and using porous polymer layers to control In mobility, Ru-In2O3 interface sites are stabilized, and ethanol can be produced with superior overall selectivity (70 %, rest CO). Our work highlights how engineering of bifunctional active ensembles enables cooperativity and synergy at tailored interfaces, which unlocks unprecedented performance in heterogeneous catalysts.

Abstract Background Advocacy regarding child health policy is a core tenet of pediatrics. Previous research has demonstrated that most pediatric providers believe collective advocacy and political involvement are essential aspects of their profession, but less is known about how pediatric providers engage with families about policy issues that impact child health. The objectives of this study were to examine providers’ perceptions and practices with regards to discussing health policy issues with families and to identify provider characteristics associated with having these discussions. Methods In this cross-sectional mixed methods study, pediatric resident physicians, attending physcians, and nurse practitioners at primary care clinics within a large academic health system were surveyed to assess (1) perceived importance of, (2) frequency of, and (3) barriers to and facilitators of health policy discussions with families. Multivariable ordinal regression was used to determine provider characteristics (including demographics, practice location, and extent of civic engagement) associated with frequency of these discussions. A subset of providers participated in subsequent focus groups designed to help interpret quantitative findings. Results The overall survey response rate was 155/394 (39%). The majority of respondents (76%) felt pediatricians should talk to families about health policy issues affecting children, but most providers (69%) reported never or rarely having these discussions. Factors associated with discussing policy issues included being an attending physician/nurse practitioner (OR 8.22, 95% CI 2.04–33.1) and urban practice setting (OR 3.85, 95% CI 1.03–14.3). Barriers included feeling uninformed about relevant issues and time constraints. In provider focus groups, four key themes emerged: (1) providers felt discussing policy issues would help inform and empower families; (2) providers frequently discussed social service programs, but rarely discussed policies governing these programs; (3) time constraints and concerns about partisan bias were a barrier to conversations; and (4) use of support staff and handouts with information about policy changes could help facilitate more frequent conversations. Conclusions Pediatric providers felt it was important to talk to families about child health policy issues, but few providers reported having such conversations in practice. Primary care practices should consider incorporating workflow changes that promote family engagement in relevant health policy discussions.

Introduction: Ischaemic Heart Diseases (IHD) are increasing at an alarming rate globally. Pharmacotherapy, the mainstay of management of IHD, has Dual Antiplatelet Therapy (DAPT) at its crux. DAPT, comprising of clopidogrel and aspirin, is used often for 12 months in medically managed Acute Coronary Syndrome (ACS). Clopidogrel being a prodrug, needs to be activated after ingestion, mainly by Cytochrome family of enzymes, for the desired pharmacological effects. Abnormal enzymes that convert clopidogrel to its active form can reduce the effectiveness of the drug. Therefore, Single Nucleotide Polymorphisms (SNPs) of the enzymes involved, would predispose the patient to therapy failure and recurrence of the illness. This study aims at identifying the presence of a genetic variant associated with clopidogrel responsiveness in patients with ACS. Aim: To estimate the frequency of CYP2C19*2 allele in patients with ACS presenting to Government Medical College, Thrissur, Kerala, India. Materials and Methods: Present study was a cross-sectional study done among 60 patients who presented to Government Medical College, Thrissur with ACS, between June 2018 to June 2019. Having obtained informed consent from the participants blood samples were collected in Ethylene diamine tetra-acetic Acid (EDTA) tubes. Samples were used to look for presence of CYP2C19*2 allele by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Out of 60 patients 38 were males and 22 were females. Most common age group was 61-65 years. The frequency of CYP2C19*2 allele was 41% in the study population and the variant genotype (AA/AG) was present in 62%. Conclusion: The variant genotype was found to be present in a high frequency in the study population implying the high risk for therapy failure in the study population. This asserts the need to probe the matter further, as the gene is also implicated in the metabolism of several other drugs. The introduction of pharmacogenomic testing prior to initiation of therapy may be therefore recommended for better treatment outcome. However, to validate the same, further studies with larger sample size may be necessary.

Purpose: Since the inception of tumor treating fields (TTFields) therapy as a Food and Drug Administration–approved treatment with known clinical efficacy against recurrent and newly diagnosed glioblastoma, various in silico modeling studies have been performed in an effort to better understand the distribution of applied electric fields throughout the human body for various malignancies or metastases. Methods and Materials: Postacquisition attenuation-corrected positron emission tomography–computed tomography image data sets from 2 patients with ovarian carcinoma were used to fully segment various intrapelvic and intra-abdominal gross anatomic structures. A 3-dimensional finite element mesh model was generated and then solved for the distribution of applied electric fields, rate of energy deposition, and current density at the clinical target volumes (CTVs) and other intrapelvic and intra-abdominal structures. Electric field-volume histograms, specific absorption rate–volume histograms, and current density-volume histograms were generated, by which plan quality metrics were derived from and used to evaluate relative differences in field coverage between models under various conditions. Results: TTFields therapy distribution throughout the pelvis and abdomen was largely heterogeneous, where specifically the field intensity at the CTV was heavily influenced by surrounding anatomic structures as well as its shape and location. The electric conductivity of the CTV had a direct effect on the field strength within itself, as did the position of the arrays on the surface of the pelvis and/or abdomen. Conclusion: The combined use of electric field-volume histograms, specific absorption rate-volume histograms, current density-volume histograms, and plan quality metrics enables a personalized method to dosimetrically evaluate patients receiving TTFields therapy for ovarian carcinoma when certain patient- and tumor-specific factors are integrated with the treatment plan.

Vancomycin induced thrombocytopenia (VIT) is an uncommon side effect of vancomycin which can manifest from mild petechiae to life-threatening bleed. Decreased renal clearance of vancomycin results in prolonged thrombocytopenia by antibody-mediated platelet destruction in the presence of vancomycin. Improvement in thrombocytopenia is achieved with the elimination of vancomycin. We describe a patient with end stage renal disease who experienced a protracted course of thrombocytopenia from vancomycin. We illustrate the mechanism of thrombocytopenia and the treatment modalities used by us and those described in literature. VIT is an important differential in patients with thrombocytopenia admitted to the hospital.

A novel algorithm for joint user selection and optimal power allocation for Stackelberg game‐based revenue maximization in a downlink non‐orthogonal multiple access (NOMA) network is proposed in this study. The condition for the existence of optimal solution is derived by assuming perfect channel state information (CSI) at the transmitter. The Lagrange multiplier method is used to convert the revenue maximization problem into a set of quadratic equations that are reduced to a regular chain of expressions. The optimal solution is obtained via a univariate iterative procedure. A simple algorithm for joint optimal user selection and power calculation is presented and exhibits extremely low complexity. Furthermore, an outage analysis is presented to evaluate the performance degradation when perfect CSI is not available. The simulation results indicate that at 5‐dB signal‐to‐noise ratio (SNR), revenue of the base station improves by at least 15.2% for the proposed algorithm when compared to suboptimal schemes. Other performance metrics of NOMA, such as individual user‐rates, fairness index, and outage probability, approach near‐optimal values at moderate to high SNRs.

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Women are at increased risk for cardiovascular disease (CVD) compared with men. While traditional risk factors for CVD seem to disproportionately affect women and contribute to this disparity, increased prevalence of CVD at midlife calls into question the contribution of menopause. Given the potential role that declining hormone levels play in this transition, menopause hormone therapies (MHT) have been proposed as a strategy for risk factor reduction. Unfortunately, trials have not consistently shown cardiovascular benefit with use, and several describe significant risks. Notably, the timing of hormone administration seems to play a role in its relative risks and benefits. At present, MHT is not recommended for primary or secondary prevention of CVD. For women who may benefit from the associated vasomotor, genitourinary, and/or bone health properties of MHT, CVD risks should be taken into account prior to administration. Further research is needed to assess routes, dosing, and formulations of MHT in order to elucidate appropriate timing for administration. Here, we aim to review both traditional and sex-specific risk factors contributing to increased CVD risk in women with a focus on menopause, understand cardiovascular effects of MHT through a review of several landmark clinical trials, summarize guidelines for appropriate MHT use, and discuss a comprehensive strategy for reducing CV risk in women.

Heterogenous missense variants in ACTG2 have been identified in individuals with visceral myopathy and megacystis, microcolon, intestinal hypoperistalsis syndrome (MMIHS). Though varying degrees of severity of chronic intestinal pseudo obstruction have been correlated to the disease phenotype when ACTG2 is mutated, little is known about the details of motility disorder affecting different regions of the gastrointestinal tract. This is a case series of 5 patients, age 9 months to 9 years, with ACTG2 mutations who underwent gastrointestinal manometry testing at an academic pediatric hospital. Esophageal manometry was performed in two patients with p.R257C mutations. Each was abnormal. Antral fed response with low amplitude response to azithromycin was found in one patient with a p.R257H mutation. Antral activity differed in the patients with p.R257C mutations, two having normal gastric motility (contractions in response to feeding and normal response to erythromycin), and the other having gastric dysmotility (absent fed response and no response to erythromycin). Small bowel and colonic motility did not differ significantly among patients. All patients required gastrostomy tubes and diverting ileostomies, with differing reliance on supplemental parenteral nutrition. These findings suggest that ACTG2 mutations can have varied manometric presentations within different segments of the gastrointestinal tract, which may translate to differing patient outcomes.