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Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.

Summary: Fruit development can be generally classified into a set of biologically sequential stages including fruit initiation, growth, and ripening. Cucumber, a globally important vegetable crop, displays two important features during fruit development: parthenocarpy at fruit initiation and prematurity at harvest for consumption. Therefore, fruit growth plays essential role for cucumber yield and quality formation, and has become the research hot spot in cucumber fruit development. Here, we describe recent advances in molecular mechanisms underlying fruit growth in cucumber, include key players and regulatory networks controlling fruit length variation, fruit neck elongation, and locule development. We also provide insights into future directions for scientific research and breeding strategies in cucumber. [ABSTRACT FROM AUTHOR]

Background: Alterations in EEG activity have been considered valid endophenotypes of substance use disorders (SUDs). Empirical evidence has supported the association between genetic factors (e.g., genes, single nucleotide polymorphisms [SNPs]) and SUDs, considering both clinical samples and individuals with a positive family history of SUDs [F+SUD]). Nevertheless, the relationship between genetic factors and intermediate phenotypes (i.e., altered EEG activity) among individuals with SUD phenotypes remains unclear. Objective(s): The current study aims at summarizing genetic factors linked to aberrant EEG activity among individuals with SUDs and those with F+SUD. Methods: Sixteen studies (5 [N = 986] + 11 from the Collaborative Studies On Genetics of Alcoholism [COGA] sample [432 ≤ N ≤ 8810]) were included for a qualitative systematic review. Thirteen studies (5 + 8 studies from the COGA sample) were used for multi-level meta-analytic procedures. Results: Qualitative analyses highlighted a multivariate genetic architecture linked to alterations in EEG waves among individuals with SUD phenotypes (i.e., augmented resting-state beta waves; reduced resting-state alpha waves; reduced resting-state and task-dependent theta waves). The most recurrent genetic factors were involved in cellular energy homeostasis, modulation of inhibitory and excitatory neural activity together with neural cell growth. Meta-analytic results showed a moderate association between genetic factors and altered resting-state and task-dependent EEG activity. Meta-analytic results also suggested non-additive genetic effects on altered EEG activity. Conclusions: Complex genetic interactions mediating neural activity and brain development might constitute a causal pathway toward intermediate phenotypes associated with phenotypic features, which in turn are linked to SUDs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate the genetic determinants affecting the rate of change in CSF total tau (t-tau). METHODS: This study conducted a genome-wide association study (GWAS) on longitudinal CSF t-tau and genotype data from 319 non-Hispanic Caucasians within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The aim was to identify genetic determinants influencing the rate of change in CSF t-tau, a key biomarker in AD. RESULTS: The GWAS identified a significant single nucleotide polymorphism (SNP), rs17149074, within the C9orf171 (CFAP77) gene region that showed significant association with changes in CSF t-tau over time. Additionally, five other SNPs--rs10916844, rs10916846, rs9425869, rs3744474, and rs8078303--were found to potentially influence CSF t-tau variability. CONCLUSIONS: These findings not only enhance our understanding of t-tau's progression in AD but also suggest that these identified SNPs could serve as novel genetic biomarkers, potentially providing novel insights in the prognostic landscape of AD by refining the predictive value of CSF-tau measurements [ABSTRACT FROM AUTHOR]

Introduction: Remission rates for ulcerative colitis (UC) remain low despite significant progress in disease understanding and the introduction of novel therapeutic agents. Several challenges contribute to this, including the heterogeneity of the disease, suboptimal efficacy of current diagnostic and therapeutic tools, drug safety concerns, and limited access to newer treatment options. Areas covered: This review evaluates current treatment targets in UC, assessing the effectiveness of various therapies and management strategies in achieving remission. We explore the potential role of personalized medicine, which tailors treatment based on clinical predictors, genetic factors, and immunologic profiles. Personalized approaches show promise in improving remission rates by addressing the unique characteristics of each patient. We also discussed the feasibility of adapting such management models and suggested solutions to some of the challenges in their implementation. Expert opinion: Future efforts should prioritize the continued development of biologics, small molecules, and digital health solutions, alongside noninvasive monitoring techniques. These innovations could not only enhance patient outcomes by improving remission rates but also reduce healthcare costs by minimizing hospitalization and surgical interventions. Ultimately, a personalized, stratified approach to UC management is key to optimizing patient care and addressing the unmet needs in this field. [ABSTRACT FROM AUTHOR]

Migraine is a multidimensional disease affecting a large portion of the human population presenting with a variety of symptoms. In the era of personalized medicine, successful migraine treatment presents a challenge, as several studies have shown the impact of a patient's genetic profile on therapy response. However, with the emergence of contemporary treatment options, there is promise for improved outcomes. A literature search was conducted in PubMed and Scopus, in order to obtain studies investigating the impact of genetic factors on migraine therapy outcome. Overall, 23 studies were included in the current review, exhibiting diversity in the treatments used and the genetic variants investigated. Divergent genes were assessed for each category of migraine treatment. Several genetic factors were identified to contribute to the heterogeneous response to treatment. SNPs related to pharmacodynamic receptors, pharmacogenetics and migraine susceptibility loci were the most investigated variants, revealing some interesting significant results. To date, various associations have been recorded correlating the impact of genetic factors on migraine treatment responses. More extensive research needs to take place with the aim of shedding light on the labyrinthine effects of genetic variations on migraine treatment, and, consequently, these findings can promptly affect migraine treatment and improve migraine patients' life quality in the vision of precise medicine. [ABSTRACT FROM AUTHOR]

Objective: To optimize the algorithm for early diagnosis of urolithiasis (UL) in children, considering risk factors, clinical and functional characteristics of the disease, and immunogenetic predisposition in an outpatient setting Methods: The literature on managing children with UL outside the hospital was thoroughly analyzed to achieve the goal. Medical records, risk factors, including immunogenetic predisposition, and clinical and laboratory investigation results of 652 hospitalized children with UL were studied. Additionally, a retrospective study of 379 outpatient records (the control group) and a prospective study of 1275 children (the study group) aged 1 to 18 was conducted. Based on the outpatient records analysis, the effectiveness of current and optimized management algorithms for children with UL was compared Results: As a result of the research, an algorithm for early diagnosis and prediction of UL in children, considering risk factors, including immunogenetic predisposition, was developed. The algorithm evaluates the risk of developing UL based on a thirteen-point checklist that assesses benefits and risks to provide a personalized risk score for each child. Based on this risk score, additional therapeutic interventions are determined for each patient Conclusion: The algorithm developed for early diagnosis and prediction of UL in children helps identify the condition at a preclinical stage in an outpatient setting. This algorithm categorizes patients into low-, moderate-, or high-risk groups and guides their management accordingly

Abstract In thrombotic diseases, coagulation, anticoagulation, and fibrinolysis are three key physiological processes that interact to maintain blood in an appropriate state within blood vessels. When these processes become imbalanced, such as excessive coagulation or reduced anticoagulant function, it can lead to the formation of blood clots. Genetic factors play a significant role in the onset of thrombotic diseases and exhibit regional and ethnic variations. The decision of whether to initiate prophylactic anticoagulant therapy is a matter that clinicians must carefully consider, leading to the development of various thrombotic risk assessment scales in clinical practice. Given the considerable heterogeneity in clinical diagnosis and treatment, researchers are exploring the application of artificial intelligence in medicine, including disease prediction, diagnosis, treatment, prevention, and patient management. This paper reviews the research progress on various genetic factors involved in thrombotic diseases, analyzes the advantages and disadvantages of commonly used thrombotic risk assessment scales and the characteristics of ideal scoring scales, and explores the application of artificial intelligence in the medical field, along with its future prospects.

Identification of the genetic features that determine a patient’s individual response to a medicinal product and provision of this information to a doctor helps to predict the effectiveness of therapy and the risk of adverse drug reactions. Dmitry A. Sychev — Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Full Professor, Rector of the Russian Medical Academy of Continuous Professional Education — talks about the importance of a personalised approach to selecting medicinal products and methods for their efficacy and safety control.

Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide and it remains a leading cause of kidney failure. Clinical manifestations of IgA are exacerbated by infections, and emerging data suggest that aberrant mucosal immune responses are important contributors to the immunopathogenesis of this disease. However, the exact stimuli, location and mechanism of nephritis-inducing IgA production remains unclear. In this focused review we explore recent developments in our understanding of the contribution of the mucosal immune system and mucosal-derived IgA-producing cells to the development of IgAN. [ABSTRACT FROM AUTHOR]

Celiac disease is an immune-mediated enteropathy with typical symptoms of weight loss, abdominal bloating, diarrhea, vomiting, or constipation. Many shreds of evidence show that CeD is hereditary in origin and various biochemical pathways have been connected to its etiology. Numerous genes from different physiological pathways have been investigated in the last few decades, however a comprehensive analysis is required to address the gaps and provide a more integrated understanding of how these genetic factors contribute to the pathogenesis of disease. Present study attempts to summarize the historical and up-to-date findings to understand the role of genetics in Celiac disease. The literature was searched from sources such as PubMed and Google Scholar to analyze studies conducted on celiac disease from the years 1995 to 2024. Term maps were created to examine the frequency of studies related to various terms to understand the major focus of the studies till date. The study also concise the different genetic polymorphisms studied in a table to understand the role of genetics in celiac diseases. Early studies on celiac disease primarily focused on its pathophysiology, prevalence, and general aspects, with limited attention to genetics. However, recent studies have increasingly emphasized the genetic basis of the disease and highlighting the involvement of various pathways like inflammation, T-cell differentiation and activation, epithelial barrier function, stress and apoptosis pathways. However, present study indicate that most current research predominantly focus on cytokines, specifically the TNF alpha gene. Consequently, there is a need for additional research to gain a more comprehensive understanding of the genetics of celiac disease. [ABSTRACT FROM AUTHOR]

Dairy products, a major source of calcium, demonstrate a number of beneficial effects, not only protecting against the development of osteoporosis (OP) but also suppressing the onset of type-2 diabetes (T2DM) and improving bone mineral density (BMD). Dairy consumption is closely linked to lactose tolerance. One of the genetic factors predisposing individuals to lactose intolerance is rs4988235 polymorphism of the MCM6 gene. The aim of this reported study was to analyse the relationship between the rs4988235 variant of the MCM6 gene and bone mineral density and the risk of type-2 diabetes in women after menopause. Methods: The study was conducted among 607 female patients in the postmenopausal period in whom bone densitometry and vitamin-D3 levels were assayed and genotyping of the rs4988235 polymorphism of MCM6 gene was performed. The obtained results were analysed for the presence of T2DM, obesity surrogates, medical data, and past medical history. Results: The distribution of genotype frequencies was consistent with the Hardy–Weinberg equilibrium (p > 0.050). Postmenopausal women with the GG homozygote of rs4988235 polymorphism consumed significantly less calcium (dairy), which was probably related to the observed lactose intolerance. The GG homozygote of women with rs4988235 polymorphism was significantly more likely to have T2DM relative to the A allele carriers (p = 0.023). GG homozygotes had significantly lower femoral–vertebral mineral density despite the significantly more frequent supplementation with calcium preparations (p = 0.010), vitamin D (p = 0.01), and anti-osteoporotic drugs (p = 0.040). The obtained results indicate a stronger loss of femoral-neck mineral density with age in the GG homozygotes relative to the A allele carriers (p = 0.038). Conclusions: In the population of women after menopause, the carriage of the G allele of rs4988235 polymorphism of the MCM6 gene, i.e., among the patients with lactose intolerance, significantly increased the risk of developing T2DM and the loss of BMD. [ABSTRACT FROM AUTHOR]

The study explores the intricate biochemical mechanisms driving aging and their inferences for prolonged existence and to identify implicit remedial targets for interventions that promote healthier aging. A comprehensive literature investigation was conducted across different databases and search machines to identify material exploration papers, reviews, and studies concentrated on critical biochemical mechanisms driving aging. Data abstraction and synthesis were performed to organize findings into thematic sections, each devoted to a specific biochemical mechanism. The connection of these mechanisms and their relative influence on aging were investigated, and consequences for age-associated conditions and implicit strategies to enhance health span and lifetime were explored. The review highlights the pivotal function of cellular anility, genomic integrity, mitochondrial function, inflammation, genetics, epigenetic regulation, and nutrient seeing in shaping the aging process. Transcriptional processes, including RNA polymerase II extension speed and chromatin structure, are also intertwined in aging. Sirtuins, NAD, and circadian timepieces regulate lifetime and health span, while exercise and nutrition play pivotal functions in maintaining cellular health. Drugs targeting aging pathways and biomarkers for assessing aging processes show capacity. This study provides a comprehensive understanding of the molecular mechanisms underpinning aging and lifetime regulation, stressing the significance of interdisciplinary exploration in addressing the complex challenges of aging. The known biochemical mechanisms offer implicit remedial targets for interventions promoting healthier aging and extended life. Evolving trends and impending directions in longevity research are bandied, and limitations and challenges in deciphering exploration issues into practical interventions are addressed. [ABSTRACT FROM AUTHOR]

The development of antibiotic resistance in Staphylococcus aureus, particularly in methicillin-resistant S. aureus (MRSA), has become a significant health concern worldwide. The acquired mecA gene encodes penicillin-binding protein 2a (PBP2a), which takes over the activities of endogenous PBPs and, due to its low affinity for β-lactam antibiotics, is the main determinant of MRSA. In addition to PBP2a, other genetic factors that regulate cell wall synthesis, cell signaling pathways, and metabolism are required to develop high-level β-lactam resistance in MRSA. Although several genetic factors that modulate β-lactam resistance have been identified, it remains unclear how they alter PBP2a expression and affect antibiotic resistance. This review describes the molecular determinants of β-lactam resistance in MRSA, with a focus on recent developments in our understanding of the role of mecA-encoded PBP2a and on other genetic factors that modulate the level of β-lactam resistance. Understanding the molecular determinants of β-lactam resistance can aid in developing novel strategies to combat MRSA. [ABSTRACT FROM AUTHOR]

In thrombotic diseases, coagulation, anticoagulation, and fibrinolysis are three key physiological processes that interact to maintain blood in an appropriate state within blood vessels. When these processes become imbalanced, such as excessive coagulation or reduced anticoagulant function, it can lead to the formation of blood clots. Genetic factors play a significant role in the onset of thrombotic diseases and exhibit regional and ethnic variations. The decision of whether to initiate prophylactic anticoagulant therapy is a matter that clinicians must carefully consider, leading to the development of various thrombotic risk assessment scales in clinical practice. Given the considerable heterogeneity in clinical diagnosis and treatment, researchers are exploring the application of artificial intelligence in medicine, including disease prediction, diagnosis, treatment, prevention, and patient management. This paper reviews the research progress on various genetic factors involved in thrombotic diseases, analyzes the advantages and disadvantages of commonly used thrombotic risk assessment scales and the characteristics of ideal scoring scales, and explores the application of artificial intelligence in the medical field, along with its future prospects. [ABSTRACT FROM AUTHOR]

Introduction: The impact of the COVID-19 pandemic on head and neck cancer (HNC) has been suggested, but the causal relationship remains unclear. Methods: We explore this connection by utilizing the Mendelian randomization (MR) approach applied to publicly available genome-wide association study (GWAS) summary datasets for COVID-19 and HNC. The datasets included critical COVID-19 (13,769 cases, 1,072,442 controls), hospitalized COVID-19 (32,519 cases, 2,062,805 controls), SARS-CoV-2 infection (122,616 cases, 2,475,240 controls), and HNC (2,131 cases, 287,137 controls). Mechanistic underpinnings of the causal relationships identified by MR analysis were explored through functional annotation augmented by AI-based literature data mining. Results: Surprisingly, a genetic predisposition to contracting a milder form of COVID-19 substantially reduced the risks of developing HNC (OR: 0.52, 95% CI: 0.35-0.78, p = 1.42E-03), with no significant association between genetic liability to severe COVID-19 and the risk of HNC detected. Additionally, our findings highlighted 14 genes linked to SARS-CoV-2 infection, potentially playing a protective role in the context of HNC. These genes include OAS1, LOC107985887, BCL11A, DPP9, LOC107984685, LINC02326, MUC4, NXPE3, IFNAR2, LZTFL1, LOC105372437, NAPSA, LOC105376622, LOC107986082, and SLC6A20. Conclusion: Our study emphasizes the protective role of the genetic liability to milder COVID-19 in reducing the risk of HNC while refuting a causal relationship between severe COVID-19 and HNC. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to develop a combined predictive model for early pubertal development (EPD) in girls based on both non-genetic and genetic factors. Methods: The case-control study encompassed 147 girls diagnosed with EPD and 256 girls who exhibited normal pubertal development. The non-genetic risk score (NGRS) was calculated based on 6 independent biochemical predictors screened by multivariate logistic regressions, and the genetic risk score (GRS) was constructed using 28 EPD related single-nucleotide polymorphisms (SNPs). Area under receiver operator characteristic curve (AROC), net reclassification optimization index (NRI) and integration differentiation index (IDI) were used to evaluate the improvement of adding genetic variants to the non-genetic risk model. Results: Overweight (OR=2.74), longer electronic screen time (OR=1.79) and higher ratio of plastic bottled water (OR=1.01) were potential risk factors, and longer exercise time (OR=0.51) and longer day sleeping time (OR=0.97) were protective factors for EPD, and the AROC of NGRS model was 83.6% (79.3-87.9%). The GRS showed a significant association with EPD (OR=1.90), and the AROC of GRS model was 65.3% (59.7-70.8%). After adding GRS to the NGRS model, the AROC significantly increased to 85.7% (81.7-89.6%) (P=0.020), and the reclassification significantly improved, with NRI of 8.19% (P= 0.023) and IDI of 4.22% (P <0.001). Conclusions: We established a combined prediction model of EPD in girls. Adding genetic variants to the non-genetic risk model brought modest improvement. However, the non-genetic factors such as overweight and living habits have higher predictive utility. [ABSTRACT FROM AUTHOR]

Mithun (Bos frontalis), a domestically raised herbivore, holds significant economic importance for the farming community of Northeast India. This study aimed to elucidate the genetic parameters governing Mithun body weight traits across different ages using data from the sole organized semi-intensive Mithun farm in India. Information was gathered from 110 Mithuns born over a period spanning from 2011 to 2022. Body weight taken at week 1 (W1), 1-month (M1), 3-months (M3), 6-months (M6), 9-months (M9), 12-months (M12), 30-months (M30) and 45-months (M45) were considered for the study. The genetic parameters estimation employed the BLUPF90 suite of programs, incorporating univariate Gibbs sampler animal model with fixed effects; season and period of birth, and sex of the animal. Variance and covariance components, including direct additive genetic effects, were estimated. Heritability estimates for the eight body weight traits ranged from 0.47 ± 0.0050 to 0.50 ± 0.0043, indicating varying genetic influence across growth stages. Results revealed that Mithun herd has a substantial genetic variability for growth traits and therefore there is ample scope to select for a better growth rate. Here, we conclude that Month 12 (M12) and Month 9 (M9) body weights exhibit higher heritability, indicating potential for genetic improvement through selective breeding. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy, as a severe microvascular complication of diabetes, manifests in four clinical types: classic, albuminuria regression, a rapid decline in kidney function (RDKF), and non-proteinuric or non-albuminuric DKD. Rapidly progressive diabetic nephropathy advances to end-stage renal disease more swiftly than the typical form, posing significant risks. However, a comprehensive understanding of rapidly progressive diabetic nephropathy is currently lacking. This article reviewed latest developments in genetic and clinical risk factors associated with rapidly progressive diabetic nephropathy, aiming to broad perspectives concerning the diagnosis and interventions of this condition.

Amr Molla,1 Abdulfatah M Alayoubi,2 Raed Jannadi3 1Department of Medicine, College of Medicine, Taibah University, Madinah, Saudi Arabia; 2Department of Basic Medical Sciences, College of Medicine, Taibah University, Madinah, Saudi Arabia; 3Department of Family & Community Medicine &, Medical Education, College of Medicine, Taibah University, Madinah, Saudi ArabiaCorrespondence: Amr Molla, Universities Road, P.O. Box: 344, Taibah, Madinah, 42353, Saudi Arabia, Tel +966504342992, Email amolla@taibahu.edu.saBackground: Vitiligo, a condition characterized by depigmented skin, has been observed to have a higher incidence in patients with a family history of the disease. This study investigates the relationship between parental consanguinity, family medical history, and the onset of childhood vitiligo, hypothesizing that genetic factors play a significant role.Methods: A cross-sectional study was conducted involving 382 people diagnosed with vitiligo in Saudi Arabia. The study assessed the prevalence of parental consanguinity and its correlation with the disease’s onset, employing statistical analysis to evaluate the data collected through medical records and family history questionnaires.Results: The findings reveal a significant association between parental consanguinity, particularly among first cousins, and the incidence of childhood-onset vitiligo. Additionally, a notable correlation was found between family medical history and the onset of the condition, with familial vitiligo being more prevalent in patients with adult-onset vitiligo.Conclusion: This study underscores the critical role of genetic predispositions in the development of childhood-onset vitiligo, highlighting the influence of parental consanguinity. The results advocate for increased awareness and screening in populations with high rates of consanguinity to facilitate early detection and management of vitiligo. Future research should focus on exploring the genetic mechanisms underlying this association to develop targeted interventions.Keywords: parental consanguinity, childhood-onset vitiligo, genetic factors, familial vitiligo, Saudi Arabia, cross-sectional study

The coronavirus disease-2019 (COVID-19) has been declared a global pandemic by the World Health Organization due to its spread to more than 90% of nations of the world with significant consequences on their health, social structure, and economy. The causative agent, severe acute respiratory syndrome coronavirus 2, is a highly contagious virus of the coronaviridae family that is known to survive on many surfaces for days at various temperatures. It is acid stable at a high titer (1.2 × 103 PFU) for up to an hour and inactivated when exposed to temperatures 33°C and above for up to 30 min. Chemical agents such as ethanol, diethyl ether, chlorine, per-acetic acid, and chloroform likewise inactivate it as well as exposure to ultraviolet (UV) rays at 254 nm. Emerging evidence indicate that while modes of transmission of the disease are the same across the globe, incidence rates, clinical manifestation, severity, and outcome of COVID-19 in tropical Africa differ from other continent. Patients in Africa have presented with less severe symptoms, higher rates of recovery, and lower case-fatality rates. There are suggestions that higher environmental temperature and humidity in African countries, immune status, dietary pattern, and sociocultural practices of the people may have contributed to this. This review of literature sought to investigate the probable influence of these factors on the impact of COVID-19 in Africa with recommendations to mitigate its spread and impact on morbidity and mortality.

Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment. [ABSTRACT FROM AUTHOR]

Background: Dual-systems models, positing an interaction between two distinct and competing systems (i.e. top-down self-control, and bottom-up reward- or emotion-based drive), provide a parsimonious framework for investigating the interplay between cortical and subcortical brain regions relevant to impulsive personality traits (IPTs) and their associations with psychopathology. Despite recent developments in multivariate analysis of genome-wide association studies (GWAS), molecular genetic investigations of these models have not been conducted. Methods: Using IPT GWAS, we conducted confirmatory genomic structural equation models (GenomicSEM) to empirically evaluate dual-systems models of the genetic architecture of IPTs. Genetic correlations between dual-systems factors and relevant cortical and subcortical neuroimaging phenotypes (regional/structural volume, cortical surface area, cortical thickness) were estimated and compared. Results: GenomicSEM dual-systems models underscored important sources of shared and unique genetic variance between top-down and bottom-up constructs. Specifically, a dual-systems genomic model consisting of sensation seeking and lack of self-control factors demonstrated distinct but related sources of genetic influences (rg = 0.60). Genetic correlation analyses provided evidence of differential associations between dual-systems factors and cortical neuroimaging phenotypes (e.g. lack of self-control negatively associated with cortical thickness, sensation seeking positively associated with cortical surface area). No significant associations were observed with subcortical phenotypes. Conclusions: Dual-systems models of the genetic architecture of IPTs tested were consistent with study hypotheses, but associations with relevant neuroimaging phenotypes were mixed (e.g. no associations with subcortical volumes). Findings demonstrate the utility of dual-systems models for studying IPT genetic influences, but also highlight potential limitations as a framework for interpreting IPTs as endophenotypes for psychopathology. [ABSTRACT FROM AUTHOR]

Environments shape people, and at the same time, people are attracted to environments that fit their characteristics because fit facilitates the achievement of people's desired life outcomes, such as relationship satisfaction, work success, and well-being. In this article, we outline how persons and environments can fit, the relevance of fit and misfit for different life outcomes, and the benefits and pitfalls of different (mis)fit measures. We propose three directions for future research: (a) the use of both subjective and objective (mis)fit measures; (b) the consideration of complex dynamics between person and environment characteristics via pathways through multiple biological, experiential, behavioral, and social layers across the life span; and (c) the integration of insights from different disciplines, including psychology, sociology, neuroscience, and genetics, to move the field forward. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a socially significant disease with increasing prevalence worldwide. It is characterized by heterogeneous metabolic disorders and is associated with various risk factors, including BMI, abnormal lipid levels, hypertension, smoking, dietary preferences, physical inactivity, sedentary lifestyle, family history of diabetes, prediabetes or gestational diabetes, inflammation, intrauterine environment, age, sex, ethnicity, and socioeconomic status. Assessing the genetic risk of developing T2DM in specific populations remains relevant. The ADIPOQ gene, encoding adiponectin, is directly related to the risk of developing T2DM, obesity, and cardiovascular diseases. Our study demonstrated significant associations of ADIPOQ gene polymorphisms with the risk of developing T2DM and obesity, as well as with fasting glucose levels and BMI, in the Kazakh population. Specifically, rs266729 was significantly associated with T2DM and obesity in the Kazakh population, while other studied polymorphisms (rs1501299, rs2241766, and rs17846866) did not show a significant association. These findings suggest that ADIPOQ gene polymorphisms may influence T2DM risk factors and highlight the importance of genetic factors in T2DM development. However, further research in larger cohorts is needed to confirm these associations. [ABSTRACT FROM AUTHOR]

Background: Variants in fat mass and the obesity-associated protein (FTO) gene have long been recognized as the most significant genetic predictors of body fat mass and obesity. Nevertheless, despite the overall evidence, there are conflicting reports regarding the correlation between different polymorphisms of the FTO gene and body mass index (BMI). Additionally, it is unclear whether FTO influences metabolic syndrome (MetS) through mechanisms other than BMI's impact. In this work, we aimed to analyze the impact of the following FTO polymorphisms on the BMI as well as MetS components in a population of young adult men. Methods: The patient group consisted of 279 Polish young adult men aged 28.92 (4.28) recruited for the MAGNETIC trial. The single-nucleotide polymorphisms (SNPs), located in the first intron of the FTO gene, were genotyped, and the results were used to identify "protective" and "risk" haplotypes and diplotypes based on the literature data. Laboratory, as well as anthropometric measurements regarding MetS, were performed. Measured MetS components included those used in the definition in accordance with the current guidelines. Data regarding dietary patterns were also collected, and principal components of the dietary patterns were identified. Results: No statistically significant correlations were identified between the analyzed FTO diplotypes and BMI (p = 0.53) or other MetS components (waist circumference p = 0.55; triglycerides p = 0.72; HDL cholesterol p = 0.33; blood glucose p = 0.20; systolic blood pressure p = 0.06; diastolic blood pressure p = 0.21). Stratification by the level of physical activity or adherence to the dietary patterns also did not result in any statistically significant result. Conclusions: Some studies have shown that FTO SNPs such as rs1421085, rs1121980, rs8050136, rs9939609, and rs9930506 have an impact on the BMI or other MetS components; nevertheless, this was not replicated in this study of Polish young adult males. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative condition that displays a high prevalence in Lebanon causing a local burden in healthcare and socio-economic sectors. Unfortunately, the lack of prevalence studies and clinical trials in Lebanon minimizes the improvement of AD patient health status. In this review, we include over 155 articles to cover the different aspects of AD ranging from mechanisms to possible treatment and management tools. We highlight some important modifiable and non-modifiable risk factors of the disease including genetics, age, cardiovascular diseases, smoking, etc. Finally, we propose a hypothetical genetic synergy model between APOE4 and TREM2 genes which constitutes a potential early diagnostic tool that helps in reducing the risk of AD based on preventative measures decades before cognitive decline. The studies on AD in Lebanon and the Middle East are scarce. This review points out the importance of genetic mapping in the understanding of disease pathology which is crucial for the emergence of novel diagnostic tools. Hence, we establish a rigid basis for further research to identify the most influential genetic and environmental risk factors for the purpose of using more specific diagnostic tools and possibly adopting a local management protocol. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) poses a significant global health concern, impacting both maternal and fetal well-being. Early detection and treatment are imperative to mitigate adverse outcomes during pregnancy. This review delves into the pivotal role of insulin function and the influence of genetic variants, including SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK, in GDM development. These genetic variations affect beta-cell function and insulin activity in crucial tissues, such as muscle, disrupting glucose regulation during pregnancy. We propose a hypothesis that this variation may disrupt zinc transport, consequently impairing insulin production and secretion, thereby contributing to GDM onset. Furthermore, we discussed the involvement of inflammatory pathways, such as TNF-alpha and IL-6, in predisposing individuals to GDM. Genetic modulation of these pathways may exacerbate glucose metabolism dysregulation observed in GDM patients. We also discussed how GDM affects cardiovascular disease (CVD) through a direct correlation between pregnancy and cardiometabolic function, increasing atherosclerosis, decreased vascular function, dyslipidemia, and hypertension in women with GDM history. However, further research is imperative to unravel the intricate interplay between inflammatory pathways, genetics, and GDM. This understanding is pivotal for devising targeted gene therapies and pharmacological interventions to rectify genetic variations in SLC30A8, CDKAL1, TCF7L2, IRS1, GCK, and other pertinent genes. Ultimately, this review offers insights into the pathophysiological mechanisms of GDM, providing a foundation for developing strategies to mitigate its impact. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Home Economics of Japan is the property of Japan Society of Home Economics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Breast cancer remains a significant contributor to morbidity and mortality within oncology. Risk factors, encompassing genetic and environmental influences, significantly contribute to its prevalence. While germline mutations, notably within the BRCA genes, are commonly associated with heightened breast cancer risk, a spectrum of other variants exists among affected individuals. Diagnosis relies on imaging techniques, biopsies, biomarkers, and genetic testing, facilitating personalised risk assessment through specific scoring systems. Breast cancer screening programs employing mammography and other imaging modalities play a crucial role in early detection and management, leading to improved outcomes for affected individuals. Regular screening enables the identification of suspicious lesions or abnormalities at earlier stages, facilitating timely intervention and potentially reducing mortality rates associated with breast cancer. Genetic mutations guide screening protocols, prophylactic interventions, treatment modalities, and patient prognosis. Prophylactic measures encompass a range of interventions, including chemoprevention, hormonal inhibition, oophorectomy, and mastectomy. Despite their efficacy in mitigating breast cancer incidence, these interventions carry potential side effects and psychological implications, necessitating comprehensive counselling tailored to individual cases. [ABSTRACT FROM AUTHOR]

Copyright of Scholar Journal for Sciences & Technology is the property of Refereed Journal of Northern Europe Academy for Studies & Research (Denmark) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose of Review: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). Recent Findings: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. Summary: In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM. [ABSTRACT FROM AUTHOR]

Childhood obesity represents a pressing global public health concern due to its widespread prevalence and its close connection to early-life exposure to risk factors. The onset of obesity is contingent upon the interplay of genetic composition, lifestyle choices, and environmental as well as nutritional elements encountered during both fetal development and early childhood. This paper critically examines research discoveries in this area and concisely outlines the influence of breastfeeding on genetic predispositions associated with childhood obesity. Studies have demonstrated that breastfeeding has the potential to reduce childhood obesity by impacting anthropometric indicators. Moreover, the duration of breastfeeding is directly correlated with the degree to which it alters the risk of childhood obesity. Current explorations into the link between genetic factors transmitted through breast milk and childhood obesity predominantly focus on genes like FTO, Leptin, RXRα, PPAR-γ, and others. Numerous research endeavors have suggested that an extended period of exclusive breastfeeding is tied to a diminished likelihood of childhood obesity, particularly if sustained during the initial six months. The duration of breastfeeding also correlates with gene methylation, which could serve as the epigenetic mechanism underpinning breastfeeding's preventative influence against obesity. In summary, the thorough evaluation presented in this review underscores the intricate nature of the association between breastfeeding, genetic factors, and childhood obesity, providing valuable insights for future research efforts and policy formulation.

Ovarian carcinoma includes a wide variety of entities and appropriate subclassification is one of the chief goals in diagnostic gynecologic pathology. Over the years, several new entities have been added to the list of ovarian carcinomas. Moreover, recent advances in the pathogenesis of newer and “older” types of ovarian carcinoma have allowed for the development of ancillary studies that are important in both the subclassification and prognostication. The surgical pathologist must assimilate these new discoveries in ovarian carcinoma in addition to refining their morphology-based diagnostic skillset. The purpose of this review article is to provide an overview of specific genetic factors, clinical disease states, and microscopic queues that are important in the subclassification of ovarian carcinoma.

Chronic obstructive pulmonary disease (COPD) is a lung disease which is the third most common cause of premature death globally. Inhaling dangerous gases, cigarette smoking, and exposure to pollution are the main factors contributing to the development of COPD. These factors may harm lung tissue and create COPD causes. Increased synthesis of inflammatory mediators and proteases because of cigarette smoking exposure to transcriptional factors. Dysfunction of mitochondria essential part to lead and development of several human illnesses, such as chronic obstructive pulmonary disease. Alpha-1 antitrypsin deficiency boosts neutrophil elastase activity, which promotes tissue deterioration and emphysema (particularly in smokers because cigarette smoke also boosts protease activity). In this review, we discussed all these factors and summarized the conventional drug currently present for the treatment of COPD. In addition, we also focused on various natural compounds categorized under the flavonoids, polyphenols, alkaloids, glycosides and marine compounds which were reported for the effective treatment of COPD.

Abstract Background Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. Findings We performed a genome-wide association analysis in the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age

Chronic rhinosinusitis (CRS) is a disease caused by inflammation of the paranasal sinuses and its mucous membrane lasting for more than 4 weeks continuously. The aim of our study was to examine the main pathophysiological features of chronic IgE-mediated rhinosinusitis of bacterial etiology according to publications in the Russian Federation and in the world. A search was made through English- and Russian-language literature sources using the following databases: PubMed, MedLine, Web of Science, Russian Science Citation Index, Springer, Scopus, Scientific Research, Google Scholar, Crossref, eLibrary. The epidemiological features of CRS in the Russian Federation, bacterial pathogens and pathophysiological characteristics of CRS were analyzed. A 2-fold increase in the prevalence of CRS was registered over the past 20 years. Prevalence of the disease increases at longer age ranges. Chronic rhinosinusitis ranks first among all chronic diseases in the field of otorhinolaryngology. Allergic rhinitis, asthma, bronchiectasia, immunodeficiencies, cystic fibrosis, primary ciliary dyskinesia and autoimmune diseases are associated with CRS. The most common bacterial pathogens are S. aureus, Staphylococcus epidermidis and Propionibacterium acnes, Prevotella, Streptococcus and Veillonella, and some Gram-negative bacteria, e.g., Pseudomonas aeruginosa (P. aeruginosa), Proteus mirabilis and Klebsiella pneumoniae. Staphylococcus aureus (S. aureus) is involved in pathogenesis of nasal polyps. The colonizing bacteria may contribute to pathogenesis of CRS through the formation of biofilms. Alterations in the sino-nasal microbiome may also contribute to the development of CRS. An association of the CRS and CFTR gene mutations plays a significant role in the pathogenesis of chronic rhinosinusitis. An “immune barrier hypothesis” has been proposed as potential mechanism of CRS. Reduced expression of SPINK5, impaired STAT3 signaling, and T2R38 bitter taste receptor polymorphism have been identified in the pathogenesis of CRS. The T2R38 gene stimulates epithelial cells to produce nitrous oxide with a bactericidal effect, promotes mucociliary elimination of pathogens and prevention of upper respiratory tract infections, the polymorphism of this gene predisposes patients to gram-negative infectious diseases, and therefore is a risk factor for the development of CRS. In addition, antibody deficiency is the most common primary immunodeficiency associated with CRS.Hence, the pathogenesis of chronic IgE-mediated rhinosinusitis of bacterial etiology is associated with defects in innate immunity and mucociliary clearance, influence of the sinonasal microbiome, allergies, and genetic factors. A comprehensive assessment of these factors is necessary for the development of new preventive and therapeutic options for the correction of CRS.

Neuropathic pain is a severe and chronic condition widely found in the general population. The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients. During the processing of pain, the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation. Furthermore, the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies. Here, we will review the complex interplay between cells (satellite glial cells and inflammatory cells) and factors (cytokines, neurotrophic factors and genetic factors) that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain. More importantly, we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.