Search

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]

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.

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]

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]

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 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]

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.

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.

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

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]

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]

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]

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]

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.

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.

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]

Thrombosis is a multifaceted process involving various molecular components, including the coagulation cascade, platelet activation, platelet–endothelial interaction, anticoagulant signaling pathways, inflammatory mediators, genetic factors and the involvement of various cells such as endothelial cells, platelets and leukocytes. A comprehensive understanding of the molecular signaling pathways and cell interactions that play a role in thrombosis is essential for the development of precise therapeutic strategies for the treatment and prevention of thrombotic diseases. Ongoing research in this field is constantly uncovering new molecular players and pathways that offer opportunities for more precise interventions in the clinical setting. These molecular insights into thrombosis form the basis for the development of targeted therapeutic approaches for the treatment and prevention of thrombotic disease. The aim of this review is to provide an overview of the pathogenesis of thrombosis and to explore new therapeutic options. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The associations of the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear. METHODS: Among 26,466 UK Biobank participants, a 15‐point MIND score was calculated from 24‐hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic‐resonance‐derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations. RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3‐unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P‐trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P‐trend = 0.044) and pallidum (beta: 0.030, P‐trend = 0.033) among APOE ε4 non‐carriers (N = 654). DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long‐term brain structural changes warrants future investigation. Highlights: Adherence to the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet was significantly associated with higher volumes and larger gray matter volumes in certain brain regions in UK adults, and the associations were not modified by genetic factors.No significant associations were observed between MIND diet and longitudinal changes in the investigated brain structural markers over a median of 2.2 years.Higher MIND score was significantly associated with slower atrophy in the putamen and pallidum among APOE ε4 non‐carriers. [ABSTRACT FROM AUTHOR]

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.

This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition.

With the increasing applications of high-throughput genome sequencing technology, there is a growing recognition of the important roles of genetic factors in the occurrence and development of gynecological tumors. Genetic counseling is widely adopted in various aspects of precision medicine in tumor screening, diagnosis, treatment and prevention. From March to September 2023, more than 20 clinical experts in gynecological oncology from Gynecologic Oncology Genetic Counseling Collaboration Group, Chinese Tertiary Obstetrics and Gynecology Hospital/Materning and Child Healthcare Hospital Alliance and Integrated Chinese and Western Endometrial Cancer Professional Committee, Chinese Anti-Cancer Association, collaborated with multidisciplinary experts in epidemiology and evidence-based medicine research. Together, We conducted preliminary research on clinical issues, held special meetings with methodology experts, and convened extensive discussions with the clinical experts in gynecological oncology to draft the “expert consensus on genetic counseling in gynecological oncology (2023 edition)”. This consensus covers various aspects, including the background, characteristics and common types of hereditary tumors, genetic tumor testing, eligible populations for genetic counseling, the process and content of genetic counseling, as well as recommended resources. It follows the evidence grading system of the Oxford Centre for Evidence-Based Medicine and ultimately presents 16 expert consensus statements and recommendations. We hope that this consensus will empower clinical practitioner in gynecological oncology to better identify hereditary tumors, enabling them to provide more accurate diagnosis and treatment for patients, as well as effective preventative measures and reproductive management for their family members. This consensus will be periodically updated to align with the advancements in diagnosis and treatment of gynecological tumors and genetic counseling related fields.

Abstract Background Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. Methods In this trial, outpatients (N = 96, aged 22–65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score ≥ 20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The first participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. Discussion The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS. Trial registration ClinicalTrials.gov NCT05516095. Retrospectively registered on August 25, 2022.

Objective: To determine the genetic polymorphism associated with the development of urolithiasis (UL) in children of the Uzbek population. Methods: The study was conducted in the Specialized Children's Surgical Hospital of the Samarkand State Medical University between 2012 and 2019. In the first stage, a retrospective analysis of the case histories of 652 admitted patients was undertaken. In the second stage, 200 children aged 1 to 17 years were enrolled in the study, of which 100 were diagnosed with UL (main group), and 100 comprised the control group without UL (hospitalized for minor planned surgical interventions, such as circumcision or hernia repair). Immunogenetic studies of the vitamin D receptor (VDR), IL-1β, and IL-18 genes were carried out. Results: The obtained results indicate that polymorphism of the VDR and IL-1β genes plays an important role in susceptibility to UL. In the study groups, a statistically significant association of F/f+f/f genotypes of the VDR gene (Fok-1) with UL was found, which was 1.3 times more frequent in the main group than in the control one (p=0.033; χ2 =4.56). The C/C allele of the IL-1β gene was significantly more frequently detected in the main vs. control group (p=0.027; χ2 =7.23; df=2). The distribution of frequency of IL-18 (+105A/C) gene polymorphism for all models of inheritance was not statistically significantly different in the main and control groups (p>0.05; χ2 =3.93; df=2). Conclusion: : The role of the immunogenetic method in the detection of susceptibility to UL development was determined in the study of the distribution of polymorphic markers of the VDR and IL-1β genes, indicating the significance of the immunogenetic factors for the predisposition to UL in children of the Uzbek population which may predict the disease at its preclinical stage. Therefore, in the interests of the early diagnosis of UL in children of the Uzbek population, it is reasonable to include testing for FokI genotype and polymorphism of VDR and IL-1β genes in the complex program of examination.

Rheumatoid arthritis (RA) is an autoimmune, chronic, and genetically linked inflammatory lesion of joint tissues that is accompanied by extra-articular systemic pathologies. The disease progression leads to joints immobilization, and eventually, the patient's disability occurs approximately ten years from the first clinical manifestation. RA pathogenesis involves various mechanisms: specific joint-related damage, nonspecific adaptive, and vessel-related pathological changes. Our research aimed to study the role of peripheral blood lymphocyte apoptosis in RA pathogenesis. We have analyzed research data from Google Scholar, PubMed, Web of Science, and Scopus databases to investigate the role of lymphocyte apoptosis in RA progression. Clinical manifestations in RA are caused by autoreactive T- and B-lymphocyte activity supported by humoral and cellular immune factors activity. Disease pathogenesis is caused by an imbalance in the process of programmed cell death (apoptosis): a proportion of immune cells are rapidly destroyed. In contrast, apoptosis is inhibited in the other classes of immune cells. High infiltration of the joint by autoreactive sensitized lymphocytes worsens the patient's condition. Apoptosis inhibition is especially noticeable in the early stages of RA and correlates with the concentration of the anti-apoptotic molecule Bcl-2 in the synovia. Activating the apoptotic destruction of lymphocytes (by drug action) allows a positive therapeutic effect and sustained remission. However, it should be noted that genetic factors play a significant role in the onset, progression and drug response of RA. In addition, environmental and behavioral factors can activate RA progression and influence treatment efficacy.

Abstract Background Antisocial personality disorder (ASPD) is characterized by a lack of empathy, a sense of guiltlessness and shamelessness, as well as impulsiveness. ASPD is a relatively common psychiatric condition in the general population, whereas individuals with ASPD often have substantial social impairments and a lower quality of life, especially for those who have mental comorbidities. This review gives an overview of the etiological and clinical aspects of ASPD and critically examines ASPD from the structural, functional and biochemical perspectives. Results Twin and family studies showed genetic predisposition in ASPD. Some candidate genes associated with ASPD include SLC6A4, COMT, 5-HTR2A, TPH1, DRD2, OXTR, CACNG8, COL25A1 and several serotonergic genes. Environmental factors like adverse childhood experience (ACE) and active empathy deficits in toddlerhood play a role in the etiology of ASPD, whereas low intelligence or attainment, a large family size, a convicted parent, a disrupted family, and a young mother are predictors of antisocial personality. Structural abnormalities involving the corpus callosum, amygdala, putamen, anterior cingulate cortex, as well as orbitofrontal- and dorsolateral frontal cortices have been identified in ASPD. Other observed structural changes include a decrease in grey matter volume, whole-brain volume, and white matter volume and thickness. In addition, functional abnormalities involving autonomic activity, prefrontal functions, as well as brain functional networks like sensorimotor networks, cognitive networks and cortico-striatal connectivity have been reported. Biochemical factors associated with ASPD include fatty acid amide hydrolase (FAAH) reduction in the amygdala, as well as changes in plasma levels of inflammatory biomarkers and neurotropic factors [namely, tumor necrosis factor (TNF)-α, interleukin 10 (IL-10), transforming growth factor (TGF)-β1 and brain-derived neurotrophic factor (BNDF). Increased plasma levels of testosterone, ghrelin and cortisol and decreased levels of leptin have also been implicated in ASPD. Conclusions To date, there is no Food and Drug Administration (FDA) approved drugs for ASPD. Understanding the disease from different perspectives is important, as this provides insights into the underlying mechanisms of ASPD, whereas the associated biochemical markers can be used as potential diagnostic and treatment targets for ASPD.

Colorectal cancer (CRC) ranks among the world’s most prevalent cancers, annually claiming tens of thousands of lives. Early detection of tumor DNA in serum/plasma before metastasis can significantly enhance patient outcomes post-tumor removal. Recent advances in detecting tumor DNA in serum/plasma have catalyzed many new research directions and opportunities for molecular diagnostics. This article synthesizes data from approximately 45 research and review papers, representing the latest findings in this field. Specifically, 30 research articles from databases such as PubMed, Web of Science, Scopus, and Google Scholar were reviewed to investigate the diagnostic significance of Oct-4 in CRC. These articles focused on tissue samples from CRC and adjacent non-tumor tissues.Oct-4, an octamer-binding transcription factor, is crucial for developing embryonic stem and germ cells. Moreover, it plays a vital role in preserving cancer stem-like characteristics in specific tumor types, making it a pivotal biomarker for cancer stem cells. Our study indicates a strong association between Oct-4 expression and CRC. Primary CRC tissues, matched non-tumor tissues, and benign polyp tissues, each representing different carcinogenesis stages, were analyzed to substantiate this claim. Oct-4 expression was quantified through reverse transcription polymerase chain reaction, flow cytometry, and immunohistochemistry analyses.Furthermore, medical records of CRC patients were examined, and clinical pathology analyses were conducted to assess the correlation between Oct-4 expression and specific clinical pathology features. Findings reveal a progressive increase in Oct- 4 transcription and translation from non-tumor tissues to benign polyp tissues and from benign polyps to CRC tissues. These observations suggest that aberrant Oct-4 expression may significantly contribute to the development of CRC.

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.

Copyright of Current Neurology / Aktualno?ci Neurologiczne is the property of Medical Communications Sp. z o.o. 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.)

Background: Nevi is a common benign proliferation of melanin-producing cells. Many triggers can influence their transformation into either benign or malignant, thus it is important to understand these triggers and their incidence across different populations to take adequate prevention. Here, we aim to examine the different etiologies of nevi changes across the Jordanian population.Methods: We carried out a cross-sectional observational study focusing on patients seeking dermatological consultation for normal nevi or nevi with minimal changes. Demographic and clinical variables were collected from the patient's case history. Nevi's characteristics were also recorded. A skilled dermatologist assessed nevi morphology and changes using the ABCDE criteria for potential signs of melanoma. Nevi biopsy samples were fixed in formalin and sent for histopathological analysis and were stained with hematoxylin and eosin (H&E).Results: A total of 231 patients were enrolled, with a majority of females (85%) and a median age of 37. Past medical history was positive in 17% of the samples, with hypertension, endocrine diseases, and diabetes mellitus being the most common. The majority of patients (61%) had fewer than three nevi. Changes in nevus size, configuration, and color were reported in 10% of patients, with multiple changes observed in 36% of patients. Microscopic analysis revealed polypoidal intradermal melanocytic blue nevi as the most common histopathological finding (84%). Positive medical history and the number of nevi were significantly associated with nevi changes.Conclusion: Our results report that the number of nevi, as well as medical history, is linked to changes in their appearance. Additionally, we provide a detailed account of the various types of observed changes and their occurrence rates. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome (PCOS) is the most typical endocrine disorder affecting women worldwide. Although the etiology of PCOS is not fully understood, genetic factors are believed to play an essential role in its pathogenesis. Hence, this paper presents a review of the outcome of functional enrichment analysis of pathways associated with PCOS phenotypes for the identification of potential molecular targets as area of further research for therapeutic development for PCOS. Method It is the implementation of comprehensive literature search in database including PubMed and Google Scholar and functional analysis of genes including the HSD3B2, PPARG, PPP1R3A, LMNA, and AMH and their roles in the metabolic pathways associated with PCOS. Findings The genes including HSD3B2, PPARG, and LMNA emerged as the most important genes in relation to PCOS, suggesting that they could play key roles in regulating different aspects of PCOS pathogenesis. These findings provide valuable insights into the molecular mechanisms that underlie the complex condition of PCOS and highlight the potential of targeting these genes and their specific pathways as a promising approach to developing effective treatments for PCOS. Conclusion It was concluded that these exploring pathways associated with these genes could provide new insights into the genetic factors contributing to PCOS, and the study recommended further research on these targets for improving the health and quality of life women battling with PCOS worldwide. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition. [ABSTRACT FROM AUTHOR]

With the increasing applications of high-throughput genome sequencing technology, there is a growing recognition of the important roles of genetic factors in the occurrence and development of gynecological tumors. Genetic counseling is widely adopted in various aspects of precision medicine in tumor screening, diagnosis, treatment and prevention. From March to September 2023, more than 20 clinical experts in gynecological oncology from Gynecologic Oncology Genetic Counseling Collaboration Group, Chinese Tertiary Obstetrics and Gynecology Hospital/Materning and Child Healthcare Hospital Alliance and Integrated Chinese and Western Endometrial Cancer Professional Committee, Chinese Anti-Cancer Association, collaborated with multidisciplinary experts in epidemiology and evidence-based medicine research. Together, We conducted preliminary research on clinical issues, held special meetings with methodology experts, and convened extensive discussions with the clinical experts in gynecological oncology to draft the "expert consensus on genetic counseling in gynecological oncology (2023 edition)". This consensus covers various aspects, including the background, characteristics and common types of hereditary tumors, genetic tumor testing, eligible populations for genetic counseling, the process and content of genetic counseling, as well as recommended resources. It follows the evidence grading system of the Oxford Centre for Evidence-Based Medicine and ultimately presents 16 expert consensus statements and recommendations. We hope that this consensus will empower clinical practitioner in gynecological oncology to better identify hereditary tumors, enabling them to provide more accurate diagnosis and treatment for patients, as well as effective preventative measures and reproductive management for their family members. This consensus will be periodically updated to align with the advancements in diagnosis and treatment of gynecological tumors and genetic counseling related fields. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Nicotine-containing products (NCPs) such as electronic nicotine delivery systems (ENDS) are increasingly common throughout the landscape of youth use of nicotine-containing products (NCP), and have overtaken traditional cigarette smoking modalities. This study seeks to examine the genetic and environmental influences on liability for susceptibility and initiation of ENDS and other NCPs among US children. METHODS: Data were drawn from 886 monozygotic (MZ) and dizygotic (DZ) twin pairs aged 9-10 years in the Adolescent Brain & Cognitive Development (ABCD) study at the baseline during 2016-2018. Heritability (h²) measured the proportion of the total phenotypic variation attributable to genes. Variance component models were utilized to analyze influences from the common environment (c²) and unique environmental factors (e²), taking into account correlations within twin pairs. RESULTS: The national sample included 50% females, 69.5% of non-Hispanic Whites, 12.8% of non-Hispanic Blacks, and 11.6% of Hispanics, with a mean age of 121.5 months. The twin sets were 60% DZ and 40% MZ. Heritability was low for NCP susceptibility (h²=0) and moderate for NCP initiation (h²=39%, p=0.02). The variance associated with NCP susceptibility was primarily influenced by environmental factors, especially one's unique factors (c²=37%, p<0.0001 vs e²=63%, p<0.0001). In contrast, the variance associated with NCP initiation was split across common and unique environmental factors (c²=32%, p=0.02 vs e²=29%, p=0.02). CONCLUSIONS: In the era with ENDS use surging among youth, NCP initiation remains to be a heritable trait with joint influence from the environment. NCP susceptibility is largely influenced by environmental factors, especially unique environments. Continued assessment of gene × environment interaction can better inform future youth NCP interventions. [ABSTRACT FROM AUTHOR]