A Review on Tau Targeting Biomimetics Nano Formulations: Novel Approach for Targeting Alzheimer's Diseases.

Central nervous system disorders are prevalent, profoundly debilitating, and poorly managed. Developing innovative treatments for these conditions, including Alzheimer's disease, could significantly improve patients' quality of life and reduce the future economic burden on healthcare systems. However, groundbreaking drugs for central nervous system disorders have been scarce in recent years, highlighting the pressing need for advancements in this field. One significant challenge in the realm of nanotherapeutics is ensuring the precise delivery of drugs to their intended targets due to the complex nature of Alzheimer's disease. Although numerous therapeutic approaches for Alzheimer's have been explored, most drug candidates targeting amyloid-ß have failed in clinical trials. Recent research has revealed that tau pathology can occur independently of amyloid-ß and is closely correlated with the clinical progression of Alzheimer's symptoms. This discovery suggests that tau could be a promising therapeutic target. One viable approach to managing central nervous system disorders is the administration of nanoparticles to neurons, intending to inhibit tau aggregation by directly targeting p-tau. In Alzheimer's disease, beta-amyloid plaques and neurofibrillary tau tangles hinder neuron transmission and function. The disease also triggers persistent inflammation, compromises the blood-brain barrier, leads to brain shrinkage, and causes neuronal loss. While current medications primarily manage symptoms and slow cognitive decline, there is no cure for Alzheimer's.

Prevalence of self-medication practices among pregnant women in India: A systematic review and meta-analysis.

BACKGROUND: Self-medication practice among pregnant women is a global concern. However, its understanding in the Indian context is limited due to a lack of comprehensive studies. PURPOSE: This study aimed to comprehensively assess the prevalence of self-medication, the medications used for self-medication, diseases/conditions associated with self-medication, and the reasons for self-medication among Indian pregnant women. METHODS: This study was carried out following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A thorough search was done in PubMed, Embase, and Google Scholar to find articles that were published up until May 2023. Inclusion criteria comprised observational studies reporting self-medication prevalence among pregnant women in India. Data were extracted using a standardized sheet, and a random-effects model was applied to determine the overall prevalence of self-medication using R software. The I2 statistic was employed to assess the heterogeneity among the studies. RESULTS: This study analyzed eight studies with a collective sample size of 2208 pregnant women. The pooled prevalence of self-medication among pregnant Indian women was 19.3% (95% CI: 7.5%-41.3%; I2 = 99%; p < 0.01). Common self-treated conditions were cold, cough, fever, headache, and stomach disorders. Antipyretics, analgesics, antihistamines, and antacids were frequently used for self-medication. The perception of mild ailment, immediate alleviation, convenience, time savings, and advice from family, friends, or the media were all reasons for self-medication. Local pharmacies were the most usual source for obtaining drugs, and pharmacists, family, friends, and past prescriptions were common sources of medicine information. CONCLUSIONS: A low yet substantial number of pregnant women in India are engaged in self-medication practices. Appropriate strategies need to be planned to reduce self-medication practices to attain sustainable developmental goals for maternal health in India.

Nonadherence to antiepileptic medication and associated factors among persons with epilepsy in India: A systematic review and meta-analysis.

BACKGROUND: Nonadherence to antiepileptic drugs (AEDs) is a prevalent issue in India, contributing to suboptimal seizure control, higher morbidity and mortality, increased hospitalization rates, and a substantial effect on the overall quality of life for individuals with epilepsy. OBJECTIVES: This study aimed to measure the prevalence of medication adherence among individuals with epilepsy in India and to identify factors associated with nonadherence. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Embase, and Google Scholar for studies on AED adherence in India. Quality assessment employed Newcastle Ottawa Scale adapted for cross-sectional studies. Pooled prevalence was ascertained using a random-effects model in R software (version 4.2.2), with a 95% confidence interval. Heterogeneity was estimated with the I2 statistic, and publication bias was appraised via a funnel plot. Subgroup analyses, based on study region and adherence measurement tool, were done to investigate heterogeneity. RESULTS: Nine cross-sectional studies with 1772 participants were analyzed. The pooled prevalence of adherence to AEDs in India stood at 49.9% (95% CI: 39.8%-60.1%). Subgroup analyses showed comparable adherence rates in the South (50.9%) and North (46.5%) regions of India. However, adherence rates varied substantially based on the measurement tool: Morisky Medication Adherence Scale-4 (MMAS-4) reported 71.3%, MMAS-8 indicated 45.9%, and Morisky Green Levine (MGL) adherence scale exhibited 42.0%. Factors contributing to non-adherence to antiepileptic therapies involved poor socioeconomic status, lower education levels, polytherapy, drug-related side effects, and substance abuse. CONCLUSIONS: Almost half of persons with epilepsy in India were non-adherent to their AEDs. This underscores the importance for healthcare professionals to pay greater attention to improving the adherence rate to AEDs within the healthcare service.

Shear zones in granular mixtures of hard and soft particles with high and low friction.

Granular materials show inhomogeneous flows characterized by strain localization. When strain is localized in a sheared granular material, rigid regions of a nearly undeformed state are separated by shear bands, where the material yields and flows. The characteristics of the shear bands are determined by the geometry of the system, the micromechanical material properties, and the kinematics at the particle level. For a split-bottom shear cell, recent experimental work has shown that mixtures of hard, frictional and soft, nearly frictionless particles exhibit wider shear zones than samples with only one of the two components. To explain this finding, we investigate the shear zone properties and the stress response of granular mixtures using discrete element simulations. We show that both interparticle friction and elastic modulus determine the shear-band properties and packing density of granular mixtures of various mixing ratios, but their stress response depends strongly on the interparticle friction. Our study provides a fundamental understanding of the micromechanics of shear band formation in granular mixtures.

Understanding the association between intimate partner violence and sexually transmitted infections among women in India: a propensity score matching approach.

BACKGROUND: Intimate partner violence (IPV) against women can significantly impact their overall health. While numerous studies in developing nations highlight the association between IPV and sexually transmitted infections (STIs), the evidence available within the Indian context remains limited. Therefore, this study aims to fill this knowledge gap by investigating the relationship between exposure to different forms of IPV and the occurrence of STIs, using a quasi-experimental approach. METHODS: The study used a sample of 63 851 women aged 15-49 years from the latest National Family Health Survey-5. Propensity score matching (PSM) was employed to assess the 'treatment effect' from exposure to IPV (physical, emotional or sexual) in the past 12 months on STIs. RESULTS: About 12.2% of women (95% CI: 11.7% to 12.8%) reported symptoms of STIs at the time of the survey. Approximately 31.9% (95% CI: 31.2% to 32.7%) of women reported experiencing at least one form of IPV-either physical, emotional or sexual IPV. Of all forms of IPV, physical IPV was the most prevalent, reported by 28.6%, followed by emotional IPV (13.2%) and sexual IPV (5.7%). Women who experienced any form of IPV-whether physical, sexual or emotional-reported a higher prevalence of STIs (17.8%) as compared with those who did not experience any IPV (9.5%). The findings from the PSM analysis indicated that among the three forms of IPV, the impact of sexual IPV on STIs was the most pronounced. The average treatment effect on the treated from exposure to sexual IPV on STIs was 0.15 (95% CI 0.13 to 0.17). CONCLUSION: This study provides evidence of a significant association between IPV and STIs among women in India and underscores the urgent need for intensified efforts and interventions to address both IPV and STIs, to improve the overall health and well-being of women in India.

Prevalence and determinants of anaemia among women of reproductive age in Aspirational Districts of India: an analysis of NFHS 4 and NFHS 5 data.

BACKGROUND: Over one-third of women worldwide suffer from anaemia. The prevalence of anaemia is particularly pronounced among women of reproductive age (WRA) in developing countries, such as India. No prior study has ever exclusively studied the prevalence of anaemia across the Aspirational Districts of India. Therefore, the purpose of this study was to examine the prevalence of anaemia across Aspirational Districts of India and to identify the determinants of anaemia among WRA in these districts. METHODS: From the National Family Health Survey (NFHS)-4 (2015-16) and NFHS-5 (2019-21), data on 114,444 and 108,782 women aged 15-49 from Aspirational Districts were analyzed in our study, respectively. Bivariate statistics and multivariable binary logistic regression were used to identify the determinants of anaemia. RESULTS: The national prevalence of anaemia among WRA has increased from 53% in NFHS-4 to 57% in NFHS-5 whereas anaemia among WRA in Aspirational Districts has increased from 58.7% in NFHS-4 to 61.1% in NFHS-5. Between 2015 and 2021, over 60% of Aspirational Districts experienced an increase in the prevalence of anaemia and one-fourth, specifically 29 out of 112, observed a rise by at least 10 percentage points (pp). Notably, there are significant variations in anaemia prevalence among districts, with Simdega and Udalgiri having the highest anaemia prevalence in NFHS-4 and NFHS-5 at 78.2% and 81.5%, respectively. During this period, Barpeta followed by Udalgiri of Assam have witnessed the maximum increase with 29.4% and 26.7% respectively. Moreover, pooled regression results show women with three to four children [AOR: 1.13, 95% CI: 1.08-1.17], women who breastfeed [AOR: 1.17, 95% CI: 1.13-1.20], Scheduled Tribe women [AOR: 1.39, 95% CI: 1.35-1.44], poorest women [AOR: 1.27, 95% CI: 1.22-1.33] and women those who consume fish occasionally [AOR: 1.14, 95% CI: 1.12-1.17] were more likely to be anaemic. CONCLUSION: The significant increase in anaemia among WRA in Aspirational Districts of India is a matter of concern. Given the rise in anaemia among WRA, determinants-based and district-specific measures must be designed and implemented to reduce the prevalence of anaemia among Aspirational Districts of India.

Targeting Abnormal Tau Phosphorylation for Alzheimer's Therapeutics.

Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing a formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: ß-amyloid (Aß) and tau protein. While the amyloid cascade theory has long dominated AD research, recent developments have ignited debates about its centrality. Aß plaques and tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal antibodies targeting Aß, have been approved, albeit amidst controversy, raising questions about the therapeutic efficacy of Aß-focused interventions. On the other hand, tau, specifically its hyperphosphorylation, disrupts microtubule stability and contributes to neuronal dysfunction. Various post-translational modifications of tau drive its aggregation into NFTs. Emerging treatments targeting tau, such as GSK-3ß and CDK5 inhibitors, have shown promise in preclinical and clinical studies. Restoring the equilibrium between protein kinases and phosphatases, notably protein phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily regulated by its phosphorylation state. Activation of tau-specific phosphatases offers potential for mitigating tau pathology. The evolving landscape of AD drug development emphasizes tau-centric therapies and reevaluation of the amyloid cascade hypothesis. Additionally, exploring the role of neuroinflammation and its interaction with tau pathology present promising research directions.

Gels in Motion: Recent Advancements in Energy Applications.

Gels are attracting materials for energy storage technologies. The strategic development of hydrogels with enhanced physicochemical properties, such as superior mechanical strength, flexibility, and charge transport capabilities, introduces novel prospects for advancing next-generation batteries, fuel cells, and supercapacitors. Through a refined comprehension of gelation chemistry, researchers have achieved notable progress in fabricating hydrogels endowed with stimuli-responsive, self-healing, and highly stretchable characteristics. This mini-review delineates the integration of hydrogels into batteries, fuel cells, and supercapacitors, showcasing compelling instances that underscore the versatility of hydrogels, including tailorable architectures, conductive nanostructures, 3D frameworks, and multifunctionalities. The ongoing application of creative and combinatorial approaches in functional hydrogel design is poised to yield materials with immense potential within the domain of energy storage.

Encyclopaedic Review of Glipizide Pre-clinical and Clinical Status.

Glipizide is an oral glucose-lowering medication that is beneficial for the treatment of type 2 diabetes. This study compiles exhaustively all accessible information on glipizide, from preclinical to clinical studies. Glipizide may be used in concert with TRAIL to treat cancer cells; in vitro studies have shown that it suppresses angiogenesis and vasculogenesis while shielding cells from glycation-induced damage. Anticonvulsant effects and modifications in the pharmacokinetics of other medications, such as Divalproex Sodium, were seen in glipizide in vivo experiments. Propranolol amplifies glipizide's hypoglycemic effect briefly in normal animals but consistently enhances it in diabetic ones. In the treatment of cancer and neurodegenerative poly(Q) illnesses, glipizide has demonstrated to offer potential therapeutic advantages. It is ineffective in preventing DENA-induced liver cancer and may cause DNA damage over time. The way glipizide interacts with genetic variants may increase the risk of hypoglycemia. Combining Syzygium cumini and ARBE to glipizide may enhance glycemic and lipid control in type 2 diabetes. Individuals with coronary artery disease who take glipizide or glyburide have an increased risk of death. The risk of muscular responses and acute pancreatitis is minimal when glipizide and dulaglutide are combined. In conclusion, glipizide has shown promising therapeutic efficacy across a variety of disorders.

Mechanistic Investigation of Thiazole-Based Pyruvate Kinase M2 Inhibitor Causing Tumor Regression in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a deadly breast cancer with a poor prognosis. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme in glycolysis, is abnormally highly expressed in TNBC. Overexpressed PKM2 amplifies glucose uptake, enhances lactate production, and suppresses autophagy, thereby expediting the progression of oncogenic processes. A high mortality rate demands novel chemotherapeutic regimens at once. Herein, we report the rational development of an imidazopyridine-based thiazole derivative 7d as an anticancer agent inhibiting PKM2. Nanomolar range PKM2 inhibitors with favorable drug-like properties emerged through enzyme assays. Experiments on two-dimensional (2D)/three-dimensional (3D) cell cultures, lactate release assay, surface plasmon resonance (SPR), and quantitative real-time polymerase chain reaction (qRT-PCR) validated 7d preclinically. In vivo, 7d outperformed lapatinib in tumor regression. This investigation introduces a lead-based approach characterized by its clear-cut chemistry and robust efficacy in designing an exceptionally potent inhibitor targeting PKM2, with a focus on combating TNBC.

Ferroptosis: A Frontier in Osteoporosis.

Reduced bone mass and degeneration of the microarchitecture of bone tissue are the hallmarks of osteoporosis, a bone metabolic disease that increases skeletal fragility and fracture susceptibility. Osteoporosis is primarily caused by unbalanced bone remodeling, in which bone synthesis is outpaced by bone resorption caused by osteoclasts. Along with the bone-building vitamins calcium and vitamin D, typical medications for treating osteoporosis include bisphosphonates and calcitonin. The present therapies effectively stop osteoclast activation that is too high, however they come with varying degrees of negative effects. Numerous factors can contribute to osteoporosis, which is characterized by a loss of bone mass and density due to the deterioration of the bone's microstructure, which makes the bone more fragile. As a result, it is a systemic bone condition that makes patients more likely to fracture. Interest in the function of ferroptosis in the pathophysiology of osteoporosis is developing. In this review, we go through the shape of the cell, the fundamental mechanisms of ferroptosis, the relationship between osteoclasts and osteoblasts, the association between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and the relationship between ferroptosis and postmenopausal osteoporosis. The functions of ferroptosis and osteoporosis in cellular function, signaling cascades, pharmacological inhibition, and gene silencing have been better understood thanks to recent advances in biomedical research.

Examining interventions that aim to enhance TB treatment adherence in Southeast Asia: A systematic review and meta-analysis.

BACKGROUND: Adherence is often a barrier to curative treatment of Mycobacterium tuberculosis (TB). There have been numerous interventions focused on increasing TB treatment adherence in Southeast Asia, but it is unclear if they are effective. This systematic review and meta-analysis aimed to compile and evaluate the literature on interventions designed to increase TB treatment adherence in Southeast Asia. METHODS: We searched Cochrane Library Reviews (CDSR) and Cochrane Library Trials (CENTRAL), Medline, CINAHL, Scopus, and Web of Science from 2000 to 2022 with no language restrictions. We included studies of any design conducted in Southeast Asia that implemented interventions to increase treatment completion in people diagnosed with TB and assessed completion as an outcome. We did not require a control group. Four investigators used a standardized data collection form to collate results. The heterogeneity across studies was explored by I2 statistics. We assessed bias using the Newcastle-Ottawa Scale and Cochrane ROB 2.0. We used a random effects meta-analysis to calculate a pooled risk ratio with 95% confidence intervals. RESULTS: From 1881 abstracts, we included 14 articles. There were 7198 subjects with 3163 (44%) receiving a TB treatment adherence intervention across eight countries. Interventions included directly observed therapy, text-message reminders, food incentives, and more. The risk ratio, derived from the meta-analysis of eight included studies with a control group and 6618 participants overall, was 1.04 (95% CI 1.01,1.08; I2 = 29%), favoring the interventions over controls with little concern for heterogeneity or risk of bias. When narratively assessed, the other six studies all reported increased adherence in the intervention group. DISCUSSION: The results suggested there is a small, statistically significant benefit of using interventions to promote TB treatment completion. Future research could look at additional strategies and combinations of strategies to promote adherence.

Navigating the dementia landscape: Biomarkers and emerging therapies.

The field of dementia research has witnessed significant developments in our understanding of neurodegenerative disorders, with a particular focus on Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). Dementia, a collection of symptoms arising from the degeneration of brain cells, presents a significant healthcare challenge, especially as its prevalence escalates with age. This abstract delves into the complexities of these disorders, the role of biomarkers in their diagnosis and monitoring, as well as emerging neurophysiological insights. In the context of AD, anti-amyloid therapy has gained prominence, aiming to reduce the accumulation of amyloid-beta (Aß) plaques in the brain, a hallmark of the disease. Notably, Leqembi recently received full FDA approval, marking a significant breakthrough in AD treatment. Additionally, ongoing phase 3 clinical trials are investigating novel therapies, including Masitinib and NE3107, focusing on cognitive and functional improvements in AD patients. In the realm of FTD, research has unveiled distinct neuropathological features, including the involvement of proteins like TDP-43 and progranulin, providing valuable insights into the diagnosis and management of this heterogeneous condition. Biomarkers, including neurofilaments and various tau fragments, have shown promise in enhancing diagnostic accuracy. Neurophysiological techniques, such as transcranial magnetic stimulation (TMS), have contributed to our understanding of AD and FTD. TMS has uncovered unique neurophysiological signatures, highlighting impaired plasticity, hyperexcitability, and altered connectivity in AD, while FTD displays differences in neurotransmitter systems, particularly GABAergic and glutamatergic circuits. Lastly, ongoing clinical trials in anti-amyloid therapy for AD, such as Simufilam, Solanezumab, Gantenerumab, and Remternetug, offer hope for individuals affected by this devastating disease, with the potential to alter the course of cognitive decline. These advancements collectively illuminate the evolving landscape of dementia research and the pursuit of effective treatments for these challenging conditions.

A district-level geospatial analysis of anaemia prevalence among rural men in India, 2019-21.

BACKGROUND: Despite its considerable impact on health and productivity, anemia among men has received limited attention. In a country as diverse as India, characterized by extensive geographic variations, there is a pressing need to investigate the nuanced spatial patterns of anemia prevalence among men. The identification of specific hotspots holds critical implications for policymaking, especially in rural areas, where a substantial portion of India's population resides. METHODS: The study conducted an analysis on a sample of 61,481 rural men from 707 districts of India, utilizing data from the National Family Health Survey-5 (2019-21). Various analytical techniques, including Moran's I, univariate LISA (Local Indicators of Spatial Association), bivariate LISA, and spatial regression models such as SLM (Spatial Lag Model), and SEM (Spatial Error Model) were employed to examine the geographic patterns and spatial correlates of anaemia prevalence in the study population. RESULTS: In rural India, three out of every ten men were found to be anemic. The univariate Moran's I value for anaemia was 0.66, indicating a substantial degree of spatial autocorrelation in anaemia prevalence across the districts in India. Cluster and outlier analysis identified five prominent 'hotspots' of anaemia prevalence across 97 districts, primarily concentrated in the eastern region (encompassing West Bengal, Jharkhand, and Odisha), the Dandakaranya region, the Madhya Pradesh-Maharashtra border, lower Assam, and select districts in Jammu and Kashmir. The results of SLM revealed significant positive association between anaemia prevalence at the district-level and several key factors including a higher proportion of Scheduled Tribes, men in the 49-54 years age group, men with limited or no formal education, individuals of the Muslim faith, economically disadvantaged men, and those who reported alcohol consumption. CONCLUSIONS: Substantial spatial heterogeneity in anaemia prevalence among men in rural India suggests the need for region-specific targeted interventions to reduce the burden of anaemia among men in rural India and enhance the overall health of this population.

Genetic architecture of cardiac dynamic flow volumes.

Cardiac blood flow is a critical determinant of human health. However, the definition of its genetic architecture is limited by the technical challenge of capturing dynamic flow volumes from cardiac imaging at scale. We present DeepFlow, a deep-learning system to extract cardiac flow and volumes from phase-contrast cardiac magnetic resonance imaging. A mixed-linear model applied to 37,653 individuals from the UK Biobank reveals genome-wide significant associations across cardiac dynamic flow volumes spanning from aortic forward velocity to aortic regurgitation fraction. Mendelian randomization reveals a causal role for aortic root size in aortic valve regurgitation. Among the most significant contributing variants, localizing genes (near ELN, PRDM6 and ADAMTS7) are implicated in connective tissue and blood pressure pathways. Here we show that DeepFlow cardiac flow phenotyping at scale, combined with genotyping data, reinforces the contribution of connective tissue genes, blood pressure and root size to aortic valve function.

Dyschromatopsia and contrast sensitivity changes in COVID-19 patients.

PURPOSE: To evaluate the alterations in the psycho-physical tests, contrast sensitivity (CS) and hue discrimination (total estimation score, TES) in COVID-19 patients. METHODS: A prospective case-control study was undertaken in 2021-22 to look at CS and TES among COVID-19 patients and RT-PCR negative normal subjects by a mobile app "smart optometry" and X-Rite's free online version of Farnsworth-Munsell 100 hue test. Strict visual acuity (minimum of 6/9 equivalent on Snellen) and other clinical parameters were used as exclusion criteria to filter potentially confounding pre-receptoral co-morbid conditions. The effect of mismatch in recruiting age and sex matched controls during the pandemic were analyzed by multivariate linear regression. RESULT: One-way ANOVA ruled out any influence of gender on CS and TES; however, there was significant difference in the TES on Mann Whitney U test (TES- 2.95 +/- 3.8 for cases; 0.30 +/- 1.1 for controls; p <0.001) and it persisted after accounting for age. Six controls with breakthrough infections had a significant deterioration in TES (Mean scores -3.0; 95% CI = -5.89 to -0.11; p = 0.04) on paired t test. Qualitative analysis showed that S-cone mediated deficiencies outnumber those affecting M-L cone mediated deficiencies. Among 53 subjects exhibiting three sensory features, anosmia, loss of taste and dyschromatopsia, nine (16.98%) had all features concurrently. CONCLUSION: The study demonstrates that COVID-19 infection leads to altered TES representing dyschromatopsia -an ocular counterpart of anosmia, with little difference on CS.

Achieving Order in Disorder: Stabilizing Red Light-Emitting α-Phase Formamidinium Lead Iodide.

While formamidinium lead iodide (FAPbI3) halide perovskite (HP) exhibits improved thermal stability and a wide band gap, its practical applicability is chained due to its room temperature phase transition from pure black (α-phase) to a non-perovskite yellow (δ-phase) when exposed to humidity. This phase transition is due to the fragile ionic bonding between the cationic and anionic parts of HPs during their formation. Herein, we report the synthesis of water-stable, red-light-emitting α-phase FAPbI3 nanocrystals (NCs) using five different amines to overcome these intrinsic phase instabilities. The structural, morphological, and electronic characterization were obtained using X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), and X-ray photoelectron spectroscopy (XPS), respectively. The photoluminescence (PL) emission and single-particle imaging bear the signature of dual emission in several amines, indicating a self-trapped excited state. Our simple strategy to stabilize the α-phase using various amine interfacial interactions could provide a better understanding and pave the way for a novel approach for the stabilization of perovskites for prolonged durations and their multifunctional applications.

Early-warning of Cardiac Condition through Detection of Murmur in Heart Sound - A Case Study.

Cardiovascular disease, particularly Rheumatic Heart Disease (RHD), is one of the leading causes of death in many developing countries. RHD is manageable and treatable with early detection. However, multiple countries across the globe suffer from a scarcity of experienced physicians who can perform screening at large scales. Advancements in machine learning and signal processing have paved way for Phonocardiogram (PCG)-based automatic heart sound classification. The direct implication of such methods is that it is possible to enable a person without specialized training to detect potential cardiac conditions with just a digital stethoscope. Hospitalization or life-threatening situations can be dramatically reduced via such early screenings. Towards this, we conducted a case study amongst a population from a particular geography using machine learning and deep learning methods for the detection of murmur in heart sounds. The methodology consists of first pre-processing and identifying normal vs. abnormal heart sound signals using 3 state-of-the-art methods. The second step further identifies the murmur to be systolic or diastolic by capturing the auscultation location. Abnormal findings are then sent for early attention of clinicians for proper diagnosis. The case study investigates the efficacy of the automated method employed for early screening of potential RHD and initial encouraging results of the study are presented.

Repercussion of Primary Nucleation Pathway: Dementia and Cognitive Impairment.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and prion disease, are characterized by the conversion of normally soluble proteins or peptides into aggregated amyloidal fibrils. These diseases result in the permanent loss of specific types of neurons, making them incurable and devastating. Research on animal models of memory problems mentioned in this article contributes to our knowledge of brain health and functionality. Neurodegenerative disorders, which often lead to cognitive impairment and dementia, are becoming more prevalent as global life expectancy increases. These diseases cause severe neurological impairment and neuronal death, making them highly debilitating. Exploring and understanding these complex diseases offer significant insights into the fundamental processes essential for maintaining brain health. Exploring the intricate mechanisms underlying neurodegenerative diseases not only holds promise for potential treatments but also enhances our understanding of fundamental brain health and functionality. By unraveling the complexities of these disorders, researchers can pave the way for advancements in diagnosis, treatment, and ultimately, improving the lives of individuals affected by neurodegenerative diseases.

Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.

Cocaine use disorder (CUD) is a prevalent neuropsychiatric disorder with few existing treatments. Thus, there is an unmet need for the identification of new pharmacological targets for CUD. Previous studies using environmental enrichment versus isolation paradigms have found that the latter induces increased cocaine self-administration with correlative increases in the excitability of medium spiny neurons (MSN) of the nucleus accumbens shell (NAcSh). Expanding upon these findings, we sought in the present investigation to elucidate molecular determinants of these phenomena. To that end, we first employed a secondary transcriptomic analysis and found that cocaine self-administration differentially regulates mRNA for fibroblast growth factor 13 (FGF13), which codes for a prominent auxiliary protein of the voltage-gated Na+ (Nav) channel, in the NAcSh of environmentally enriched rats (i.e., resilient behavioral phenotype) compared to environmentally isolated rats (susceptible phenotype). Based upon this finding, we used in vivo genetic silencing to study the causal functional and behavioral consequences of knocking down FGF13 in the NAcSh. Functional studies revealed that knockdown of FGF13 in the NAcSh augmented excitability of MSNs by increasing the activity of Nav channels. These electrophysiological changes were concomitant with a decrease in cocaine demand elasticity (i.e., susceptible phenotype). Taken together, these data support FGF13 as being protective against cocaine self-administration, which positions it well as a pharmacological target for CUD.