Ethnicity and Sudden Cardiac Death in Athletes: Insights from a Large United Kingdom Registry.

BACKGROUND AND AIMS: The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood. OBJECTIVES: To investigate etiology of SCD among different ethnicities in a large cohort of athletes. METHODS: Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. RESULTS: Most of athletes were white (n = 758; 89%). Black and Asian athletes were 51 (6%) and 39 (5%) respectively. A structurally normal heart, indicative of sudden arrhythmic death syndrome (SADS) was the most common autopsy finding (n = 385, 45%), followed by myocardial diseases (n = 275; 32%) cases, atherosclerotic coronary artery disease (CAD) (n = 58, 7%) and coronary artery anomalies (n = 29, 3%). In most of cases, death occurred during exercise (n = 737; 87%) . Arrhythmogenic cardiomyopathy (ACM) was more common in black (n = 13; 25%) than in white (n = 109; 14%) and Asian (n = 3; 8%) athletes (p = 0.03 between black and white athletes; p = 0.04 between black and Asian athletes); in contrast, CAD was more common in Asians (n = 6; 15% vs n = 51; 7% in whites vs 2% n = 1; in blacks, p = 0.02 between Asian and black athletes). Among white athletes, ACM was more common in individuals who died during exercise than in the ones who died at rest (p = 0.005). Such a difference was not observed in Asian and black athletes. In Asian athletes, CAD was the diagnosis at autopsy in 18% of individuals who died during exercise and in none of individuals who died at rest. CONCLUSIONS: A structurally normal heart at autopsy and myocardial diseases are the most common findings in athletes who died suddenly. While ACM is more common in black athletes, atherosclerotic CAD is more common in Asian athletes, with a strong association with exercise-induced SCD. ACM appears to be a driver of exercise-induced SCD in white athletes, however this is not the case in black and Asian athletes.

A sudden death in an athlete is an uncommon but highly tragic event which appears almost paradoxical, as athletes epitomize the healthiest segment of society. Inherited and familiar cardiac conditions are the main causes of sudden death in young individuals and athletes. Studies on this matter have mainly focused on Caucasian athletes and the frequency or the causes of sudden death in athletes of other ethnicities is largely unknown. Our study focusses on this aspect and reveals that causes of sudden death may highly vary among athletes of different race. The circumstances of death differ significantly among various ethnicities, even looking at the same underlying cardiac condition.

Novel chitosan-based smart bio-nanocomposite films incorporating TiO2 nanoparticles for white bread preservation.

Chitosan (CS)-based bio-nanocomposite food packaging films were prepared via solvent-casting method by incorporating a unique combination of additives and fillers, including polyvinyl alcohol (PVA), glycerol, Tween 80, castor oil (CO), and nano titanium dioxide (TiO2) in various proportions to enhance film properties. For a comprehensive analysis of the synthesized films, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), tensile testing, field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), and UV-vis spectrophotometry were employed. Furthermore, the antimicrobial efficacy of the films against S. aureus, E. coli, and A. niger was examined to assess their potential to preserve food from foodborne pathogens. The results claimed that the inclusion of castor oil and TiO2 nanoparticles considerably improved antimicrobial properties, UV-vis light barrier properties, thermal stability, optical transparency, and mechanical strength of the films, while reducing their water solubility, moisture content, water vapor and oxygen permeability. Based on the overall analysis, CS/PVA/CO/TiO2-0.3 film can be selected as the optimal one for practical applications. Furthermore, the practical application of the optimum film was evaluated using white bread as a model food product. The modified film successfully extended the shelf life of bread to 10 days, surpassing the performance of commercial LDPE packaging (6 days), and showed promising attributes for applications in the food packaging sector. These films exhibit superior antimicrobial properties, improved mechanical strength, and extended shelf life for food products, marking a sustainable and efficient alternative to conventional plastic packaging in both scientific research and industrial applications.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. Using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Folic acid: The key to a healthy pregnancy - A prospective study on fetomaternal outcome.

Objectives: The objective of the study is to study the fetomaternal outcome associated with folic acid deficiency in pregnancy. Materials and Methods: This hospital-based observational study was conducted in the Department of Obstetrics and Gynaecology at Base Hospital, Delhi Cantt, and a total of 351 participants were enrolled who were fulfilling the inclusion criteria. The plasma folic acid level of the selected patients was measured in the booking visit by automated chemiluminescence assay. The cutoff levels of folic acid were taken at 8.6 ng/mL. Based on these values, the study population was divided into two groups, one with folic acid values <8.6 ng/mL and the other with values ≥8.6 ng/mL. Plasma Vitamin B12 levels were measured to check for any concurrent deficiencies. Obstetric outcomes included first- and second-trimester miscarriages, development of anemia, gestational hypertension/preeclampsia, gestational diabetes mellitus, hypothyroidism, placental abruption, and intrauterine fetal growth restriction (FGR). Furthermore, the period of gestation at delivery, fetal weights, APGAR scores at 5 min were documented. The study also considered fetal neural tube defects, intrauterine fetal demise for data collection. Collected data were analyzed statistically to find the association of the above-mentioned outcomes with levels of folic acid. Results: The rate of preterm deliveries was significantly higher in the folic acid group with levels <8.6 ng/mL (16.94%). The incidence of small for gestational age/FGR was higher in the folic acid group with levels <8.6 ng/mL (27.11%) compared to the high folic acid group with levels ≥8.6 ng/mL (13.38%). The differences in the incidence of anemia, gestational hypertension, gestational diabetes, and preeclampsia between the two groups were not statistically significant and no cases of intrauterine fetal demise or placental abruption were observed in either group. Moreover, there was no significant difference in the relative risk of low Apgar scores at 5 min between the two groups. Conclusion: The present study suggests that low folic acid levels during pregnancy are associated with a higher risk of adverse pregnancy outcomes such as anemia, miscarriages, preterm delivery, and FGR. Therefore, adherence to nutritional recommendation of folic acid supplementation during pregnancy is essential to prevent these adverse outcomes.

Allometric scaling for left ventricular mass and geometry in male and female athletes of mixed and endurance sports.

BACKGROUND: The athlete's heart (AH) defines the phenotypical changes that occur in response to chronic exercise training. Echocardiographic assessment of the AH is used to calculate LV mass (LVM) and determine chamber geometry. This is, however, interpreted using standard linear (ratiometric) scaling to body surface area (BSA) whereas allometric scaling is now widely recommended. This study (1) determined whether ratiometric scaling of LVM to BSA (LVMiratio) provides a size-independent index in young and veteran athletes of mixed and endurance sports (MES), and (2) calculated size-independent beta exponents for allometrically derived (LVMiallo) to BSA and (3) describes the physiological range of LVMiallo and the classifications of LV geometry. METHODS: 1373 MES athletes consisting of young (< 35 years old) (males n = 699 and females n = 127) and veteran (> 35 years old) (males n = 327 and females n = 220) were included in the study. LVMiratio was calculated as per standard scaling and sex-specific LVMiallo were derived from the population. Cut-offs were defined and geometry was classified according to the new exponents and relative wall thickness. RESULTS: LVMiratio did not produce a size independent index. When tested across the age range the following indexes LVMi/BSA0.7663 and LVMi/BSA0.52, for males and females respectively, were size independent (r = 0.012; P = 0.7 and r = 0.003; P = 0.920). Physiological cut-offs for LVMiallo were 135 g/(m2)0.7663 in male athletes and 121 g/(m2)0.52 in female athletes. Concentric remodelling / hypertrophy was present in 3% and 0% of young male and female athletes and 24% and 17% of veteran male and female athletes, respectively. Eccentric hypertrophy was observed in 8% and 6% of young male and female athletes and 9% and 11% of veteran male and female athletes, respectively. CONCLUSION: In a large cohort of young and veteran male and female MES athletes, LVMiratio to BSA is not size independent. Sex-specific LVMiallo to BSA with LVMi/BSA0.77 and LVMi/BSA0.52 for male and female athletes respectively can be applied across the age-range. Population-based cut-offs of LVMiallo provided a physiological range demonstrating a predominance for normal geometry in all athlete groups with a greater percentage of concentric remodelling/hypertrophy occurring in veteran male and female athletes.

Triangular Osteosynthesis as a Surgical Treatment Option for Unstable Sacral Fracture Fixation with Sacroiliac Dislocation: A Case Report.

Introduction: Sacral fractures, which can occur in young individuals following road traffic accidents or falls from a height, as well as in elderly individuals with osteoporosis after minor trauma, are considered a diverse type of fracture. The incidence of non-osteoporotic sacral fractures is estimated to be 2.1/100,000 people, whereas osteoporotic fractures are estimated to affect 1-5% of elderly individuals at risk. Triangular osteosynthesis is a relatively new fixation technique used as a surgical treatment for unstable sacral fractures. It combines transverse fixation with lumbo-pelvis distraction osteosynthesis, providing stability in different planes. The subcategory of triangular osteosynthesis encompasses spinopelvic fixation, which involves the fusion of transverse sacral alar fracture fixation (such as iliosacral screw/s and sacral plate) and unilateral lumbopelvic fixation from the pedicle of L5 to the ipsilateral posterior ilium. The utilization of this technique provides a mechanically advanced approach for stabilizing unstable sacral alar fractures with vertical shear. Once the pelvic ring injury has been reduced, lumbopelvic fixation can assist in preventing the recurrence of vertical displacement in the unstable hemipelvis. Case Report: The patient, a 29-year-old male, experienced a road traffic accident resulting from a collision involving a motorcycle. As a result of the incident, he suffered from an unstable lateral compression type 1 pelvic ring injury, accompanied by an ipsilateral sacroiliac dislocation and a vertical sacral fracture on the opposite side. Computed tomography imaging revealed a right sacroiliac dissociation, a left sacral fracture classified as AO type B1, as well as fractures in both the superior and inferior pubic rami. The pelvic ring of the patient was subjected to closed reduction and percutaneous fixation, accompanied by minimally invasive spinopelvic fixation. The surgical procedure was performed in a single session, involving the reduction and fixation of the right sacroiliac dissociation, followed by lumbopelvic fixation while in the prone position. After a 1-month follow-up, the patient demonstrated the ability to walk without experiencing pain, and the X-ray revealed a stable spinopelvic and sacroiliac fixation. Conclusion: The utilization of triangular osteosynthesis fixation provides a reliable form of fixation that enables the patient to bear complete weight at an early stage of 6 weeks while also preventing any reduction loss in vertical shear transforaminal sacral fractures.

Coronary artery anomalies and the role of echocardiography in pre-participation screening of athletes: a practical guide.

Transthoracic echocardiography is an essential and widely available diagnostic tool for assessing individuals reporting cardiovascular symptoms, monitoring those with established cardiac conditions and for preparticipation screening of athletes. While its use is well-defined in hospital and clinic settings, echocardiography is increasingly being utilised in the community, including in the rapidly expanding sub-speciality of sports cardiology. There is, however, a knowledge and practical gap in the challenging area of the assessment of coronary artery anomalies, which is an important cause of sudden cardiac death, often in asymptomatic athletic individuals. To address this, we present a step-by-step guide to facilitate the recognition and assessment of anomalous coronary arteries using transthoracic echocardiography at the bedside; whilst recognising the importance of performing dedicated cross-sectional imaging, specifically coronary computed tomography (CTCA) where clinically indicated on a case-by-case basis. This guide is intended to be useful for echocardiographers and physicians in their routine clinical practice whilst recognising that echocardiography remains a highly skill-dependent technique that relies on expertise at the bedside.

Seasonal Variation in Sudden Cardiac Death: Insights from a Large United Kingdom Registry.

BACKGROUND: Sudden cardiac death (SCD) is relatively common and may occur in apparently healthy individuals. The role of seasonal variation as a risk factor for SCD is poorly understood. The aim of this study was to investigate whether SCD exhibits a predilection for specific seasons. METHODS: We reviewed a database of 4751 cases of SCD (mean age 38 ± 17 years) referred to our Center for Cardiac Pathology at St George's University of London between 2000 and 2018. Clinical information was obtained from referring coroners who were asked to complete a detailed questionnaire. All cases underwent macroscopic and histological evaluation of the heart, by expert cardiac pathologists. RESULTS: SCD was more common during winter (26%) and rarer during summer (24%), p = 0.161. Significant seasonal variation was not observed among cases of sudden arrhythmic death syndrome (SADS, 2910 cases) in which the heart is structurally normal. In contrast, a significant difference in seasonal distribution among decedents exhibiting cardiac structural abnormalities at the post-mortem examination (n = 1841) was observed. In this subgroup, SCDs occurred more frequently during winter (27 %) compared to summer (22%) (p = 0.007). In cases diagnosed with a myocardial disease (n = 1399), SCD was most common during the winter (27%) and least common during the summer (22%) (p = 0.027). CONCLUSIONS: While SADS occurs throughout the year with no seasonal variation, SCD due to structural heart disease appears to be more common during the winter. Bio-meteorological factors may be potential triggers of SCD in individuals with an underlying structural cardiac abnormality.

Yield of molecular autopsy in sudden cardiac death in athletes: data from a large registry in the UK.

AIMS: Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes. METHODS AND RESULTS: We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS. CONCLUSION: The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes.

Sudden Cardiac Death in Young Athletes: JACC State-of-the-Art Review.

Athletes epitomize the healthiest segment of society. Despite this premise, sudden cardiac death may occur in apparently healthy athletes, attracting significant attention not only in the medical community but also in laypersons and media. The incidence of sudden cardiac death is variably reported, and epidemiological burden differs among cohorts. Athletes appear to be at risk of developing fatal arrhythmias when harboring a quiescent cardiac disorder. Primary cardiomyopathies, ion channelopathies, and coronary artery anomalies are prevalent causes in young individuals. Cardiac assessment of athletes can be challenging because these individuals exhibit a plethora of electrical, structural, and functional physiological changes that overlap with cardiac pathology. A diagnosis of cardiac disease in a young athlete is not necessarily an indication to terminate competition and sports participation. International guidelines, traditionally focused on disqualification of individuals with cardiac disease, have recently adopted a more liberal attitude, based on a careful assessment of the risk and on a shared-decision making approach.

Comparison of HASTE versus EPI-Based DWI for Retinoblastoma and Correlation with Prognostic Histopathologic Parameters.

BACKGROUND AND PURPOSE: Non-EPI-based DWI has shown better performance in head and neck pathologies owing to lesser susceptibility artifacts compared with EPI-DWI. However, only sporadic studies have investigated the feasibility of non-EPI-based DWI in retinoblastoma (RB). We qualitatively and quantitively compared EPI-DWI and HASTE-DWI in RB and correlated the tumor ADC values obtained from these 2 techniques with histopathologic markers. MATERIALS AND METHODS: Twenty-one treatment-naive patients with RB underwent 1.5T orbital MR imaging. EPI-DWI and HASTE-DWI were acquired at 3 b-values (0, 500, and 1000 s/mm2). All patients subsequently underwent surgical enucleation. For qualitative image assessment, scoring of overall image quality, artifacts, tumor sharpness, and tumor conspicuity was done by using a 5-point Likert scale. Quantitative assessment included calculations of SNR, contrast-to-noise ratio (CNR), geometric distortion, and ADC. Qualitative scores were compared by using the Wilcoxon signed-rank test, and quantitative parameters were analyzed with a t test. RESULTS: All 21 patients had unilateral RB; 15 were male and 6 were female with a median age of 36 months (range, 9-72 months). On histopathology, patients had either poorly differentiated (n = 13/21) or moderately differentiated (n = 8/21) RB. Other poor prognostic markers evaluated were optic nerve invasion (n = 10/21), choroidal invasion (n = 12/21), and anterior eye segment enhancement on MRI (n = 6/21). HASTE-DWI demonstrated higher image quality scores than EPI-DWI (P < .01), except for tumor conspicuity score, which was higher for EPI-DWI (P < .001). HASTE-DWI showed lower SNR, CNR, and geometric distortion than EPI-DWI (P < .001). The average acquisition times of EPI-DWI and HASTE-DWI were ∼1 and 14 minutes, respectively. The mean tumor ADC value on EPI-DWI was 0.62 ± 0.14 × 10-3 mm2/s and on HASTE-DWI was 0.83 ± 0.17 × 10-3 mm2/s. A significant correlation between EPI-DWI and HASTE-DWI ADC values (r = 0.8; P = .01) was found. Lower ADC values were found in tumors with poor prognostic markers, but none reached a statistically significant difference. CONCLUSIONS: HASTE-DWI shows improved overall image quality; however, it lacks in terms of tumor conspicuity, SNR, CNR, and longer acquisition time compared with EPI-DWI. ADC values derived from HASTE-DWI show no advantage over EPI-DWI in correlation with histopathologic prognostic markers.

Air pollution trend in Chandigarh during 2019-2022: status and influence of meteorological factors.

The degradation of ambient air quality is a pressing global concern, and India, as a developing nation, has witnessed a rapid surge in industrial activities in recent decades. This surge has resulted in numerous Indian cities ranking among the world's most polluted urban areas. Chandigarh, strategically positioned within the Indo-Gangetic plains (IGP), has not escaped this distressing trend, experiencing a significant spike in air pollution levels. This study focuses on comprehending and addressing the air quality issues in Chandigarh, shedding light on the evolution of air pollution trends and their dependence on meteorological factors. Notably, the study reveals that, with the exception of O3, pollutant concentrations surge during the rice stubble burning season. These pollutants persist in the atmosphere for prolonged periods, exacerbating the situation during winter due to lower temperatures and heightened use of fossil fuels for heating by low-income households. In contrast, the wheat stubble burning period does not significantly impact pollutant concentrations. The study also identifies a spring peak in surface O3 concentrations, attributed to favorable high temperatures that promote the photochemical reactions responsible for this phenomenon, a distinctive feature in South Asia and the Himalayas. An examination of the connection between pollutant concentrations and meteorological parameters underscores that elevated pollutant levels, except for CO, are linked to lower relative humidity and temperatures. This suggests that current development patterns have contributed to the escalation of air pollution in Chandigarh, necessitating urgent interventions to preserve the city's aesthetics and the health of its residents. Furthermore, to model and monitor pollutant behavior in Chandigarh, more extensive and extended studies are imperative. Both short-term and long-term investigations into the environmental and health impacts of air pollutants, including primary and secondary pollutants, are of paramount importance. These endeavors are essential for the well-being of both the environment and the population of Chandigarh.

Hybrid silica nanoparticles functionalized with pyrazolone-tethered organosilane: Synthesis and application for Sn (II) ion sensing in tap water.

Pyrazolone tethered triazole functionalized organosilane and their hybrid silica nanoparticles (HSNPs) have been synthesised for the selective detection of Sn(II) using spectrophotometric techniques. The prepared compounds are characterized by FT-IR, NMR (1H and 13C), XRD, mass spectrometry and FE-SEM spectral analyses. The synthesized hybrid silica nanoparticles gave improved detection limit of 4.3 × 10-8 M and stoichiometry of complex between analyte and probe was found to be 1:1. The association constant calculated for organosilane and their HSNPs came out to be 9.54 × 104 M-1 and 7.47 × 104 M-1 while the presence of other ions showed no interference in the sensing behaviour. The results of the use of this sensing system in tap water facilitate its applicability in real samples with the recovery % more than 98.

Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report.

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late­gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.

Gene therapy: an alternative to treat Alzheimer's disease.

Alzheimer's disease (AD), a neuro-degenerative disease that primarily affects the elderly, is a worldwide phenomenon. Loss of memory, cognitive decline, behavioural changes, and many other signs are used to classify it. Various hypotheses that may contribute to Alzheimer's disease have been found during decades of survey, including tau theory, the amyloid theory, the cholinergic hypothesis, and the oxidative stress hypothesis. According to some theories, the two leading causes of AD are the accumulation of amyloid beta plaque and development of NFTs in the brain. The hippocampus and cerebral cortex are the primary sites where amyloid beta plaques gather in the body. NFT formation in the brain impairs the brain's neurons' potential of signalling. According to the age at which it manifests in a person, there are two subtypes of AD: 'LOAD (Late Onset Alzheimer's Disease)' and 'EOAD (Early Onset Alzheimer's Disease)'. Long-term research into AD treatment has resulted in the introduction of some medications that provided symptomatic relief to patients but did not alter the disease's pathophysiology, like cholinesterase inhibitors, inhibitors of tau aggregation, and monoclonal antibodies to Aß aggregation. Even though the medications did not halt the progression of AD, researchers did not discontinue their work, which lead to the introduction of gene therapy - a recently created cutting-edge method of delivering genes to target sites where they can express the intended functionalities. Viral or non-viral vectors could be used to deliver the gene, each with advantages and limitations of their own. Gene therapy is proven to be a potential disease-modifying treatment for AD. This article discusses about gene therapy, its merits and demerits and the various ways of gene delivery. Additionally, it focuses on AD as the target for treatment through gene therapy, the pathophysiology of AD, and the multiple targets for gene therapy in the treatment of AD.

Posterior Leaflet of Mitral Valve-Is it Really Tri-scalloped? -A Morphological and Morphometric Study in North Indian Cadaveric Hearts.

Background: Maintaining normal left ventricular geometry and function depends on the mitral valve's normal integrity. Irreparable damage to the mitral valve calls for its replacement using either a valve made up of biological tissue or metal, pyrolytic carbon, and similar materials. Materials and Methods: The material consists of 50 formalin-fixed adults, seemingly normal cadaveric hearts of either sex which were received from the Department of Anatomy of various institutes in the north region. These hearts were cut open to access the mitral valve in the left ventricle. Results: In this study, the posterior leaflet was semi-oval in shape being 3.72 cm wide at the base. Usually said to be tri-scalloped, interestingly, it was found so only in 56% of the hearts; being bi-scalloped in 20% and single-cusped in 16% of the hearts. Even four scallops and six scallops were observed in three (6%) and one (2%) hearts, respectively. Conclusions: To conclude, notable variation has been seen in the scallops of posterolateral cusps in the present study. The number of scallops varies greatly as single, double, three, four, or tetra-scalloped and most significant six or hexa-scalloped which has never been reported in the previous studies. To understand the rationale behind each unique architectural layout, such noticeable variations are crucial for scientists around the world. Cardiothoracic surgeons could find this information valuable for mitral valve surgery repair.

Aortic regurgitation in athletes: the challenges of echocardiographic interpretation.

BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital cardiac defect and prone to premature degeneration causing aortic regurgitation (AR). The assessment of AR in athletic individuals poses several challenges as the pathological left ventricle (LV) remodelling caused by AR may overlap with the physiological remodelling of intense exercise. The purpose of this study is to highlight these challenges, review the existing literature and discuss how to tackle these conundrums. As a real-world example, we compare the resting transthoracic echocardiographic (TTE) findings in a cohort of individuals with BAV and AR, sub-grouped into "highly active" or "lightly active". METHODS: Adult male subjects with an index TTE performed at a tertiary referral centre between 2019 and 2022 were included if the TTE confirmed a BAV and at least moderate AR. Further strict inclusion criteria were applied and parameters of valve disease severity was made in accordance with existing guidelines. Subjects completed a physical activity questionnaire over the telephone, and were classified into either group 1: "highly active" or group 2: "lightly active" based on their answers. Demographics and TTE parameters were compared between the two groups. RESULTS: 30 male subjects (mean age 44 ± 13 years) with BAV-AR were included - 17 were highly active, and 13 lightly active. There was no significant difference in age (group 1, 45 ± 12.7 years vs. group 2, 42 ± 17 years; p = 0.49), height (p = 0.45), weight (p = 0.268) or severity of AR, when quantitative assessment was possible. Group 1 had a significantly higher stroke volume (131 ± 17mls vs. 102 ± 13 mls; p = 0.027), larger LV volumes, diastolic dimensions and significantly larger bi-atrial and right ventricular size. This LV dilatation in the context of AR and athleticism poses a diagnostic and management conundrum. Despite this, none of these 17 highly active individuals demonstrated any of the traditional criteria used to consider surgery. CONCLUSION: There is significant overlap between the physiological adaptations to exercise and those caused by AR. Multi-modality imaging and stress testing can aid clinicians in diagnostic and management decisions in exercising individuals when there is discordance between AR severity and symptoms.

Detection and quantification of TIMP1 and miR-141 through RT-LAMP and TT-LAMP in serum samples during estrous cycle in buffalo.

Estrus identification is a common problem in the reproductive management of farm animals. Hence, several studies have been conducted to explore biomarkers for estrus detection. One of our previous studies identified the abundance of RNA biomarkers such as TIMP1 and miR-141 in buffalo saliva during the estrus stage. However, the level of these RNA biomarkers in buffalo serum during estrous cycle is undetected. Therefore, the present study was designed to quantify TIMP1 and miR-141 in serum during buffalo estrous cycle. Blood samples were collected in different stages of estrous cycle from four healthy cyclic buffaloes. The quantification of TIMP1 and miR-141 was performed with direct serum using RT-LAMP and TT-LAMP technologies, respectively. The LAMP amplification was confirmed by agarose gel electrophoresis and the color change was quantified in comparison to a non-template control using ImageJ software. A decreased abundance of TIMP1 at the diestrus stage and a decreasing trend of miR-141 from proestrus to diestrus stages were observed, which was further reinforced by simulated random populations generated with R programming. Specifically, TIMP1 was found significantly (P < 0.0001) abundant at estrus and metestrus stages as compared to the diestrus stage, whereas miR-141 was significantly (P < 0.001) higher during the proestrus stage as compared to the other stages of estrous cycle. The ROC curve analysis showed miR-141 to be a better biomarker than TIMP1 as it distinguished the proestrus stage from diestrus with a sensitivity and specificity of 83 % and 98 %. This study also marked the first use of TT-LAMP technology for rapid miRNA detection in livestock.

Chemistry, Biological Properties, and Bio-Analysis of Tafamidis, a New Transthyretin Stabilizer: A Systematic Review.

BACKGROUND: Cardiomyopathy is a global health crisis that affects people all over the world. Consequently, scientists felt compelled to look for and develop ever-more-powerful pharmaceuticals. For ATTR-CM, the only drug currently recommended by the European Society of Cardiology is Tafamidis. OBJECTIVES: The primary aim of this review article is to understand the chemistry, pharmacodynamic, pharmacokinetic, and bio-analytical methods available for Tafamidis Methods: A systematic review of the existing resources was accomplished up to 2022, comprising existing studies forming the database covering the existing resources from Web of Science, ScienceDirect, and PubMed. RESULTS: The review was based on a systematic review of all the existing studies used to formulate the database. The study also illustrated the PRISMA design that systematically analyses the prevalent resources. CONCLUSION: Minimal analytical techniques are observed for quantifying the Tafamidis and transthyretin kinetic stabiliser. Therapeutic, pharmacological, and analytical considerations for the novel drug Tafamidis are discussed in this review. Particular attention is paid to the many different analytical and bioanalytical methods currently available for estimating Tafamidis, and the need is highlighted to develop a straightforward, validated technique that meets green chemistry standards.