Population Studies Research Articles

Relationship between Vitamin D Levels and Sarcopenia: Insights from a Korean Population Study

Relationship between Vitamin D Levels and Sarcopenia: Insights from a Korean Population Study

Melanocortin 4 receptor mutation in obesity

Obesity is increasingly prevalent worldwide, with genetic factors contributing to its development. The hypothalamic leptin-melanocortin pathway is central to the regulation of appetite and weight; leptin activates the proopiomelanocortin neurons, leading to the production of melanocortin peptides; these in turn act on melanocortin 4 receptors (MC4R) which suppress appetite and increase energy expenditure. MC4R mutations are responsible for syndromic and non-syndromic obesity. These mutations are classified based on their impact on the receptor's life cycle: i.e. null mutations, intracellular retention, binding defects, signaling defects, and variants of unknown function. Clinical manifestations of MC4R mutations include early-onset obesity, hyperphagia, and metabolic abnormalities such as hyperinsulinemia and dyslipidemia. Management strategies for obesity due to MC4R mutations have evolved with the development of targeted therapies such as Setmelanotide, an MC4R agonist which can reduce weight and manage symptoms without adverse cardiovascular effects. Future research directions must include expansion of population studies to better understand the epidemiology of MC4R mutations, exploration of the molecular mechanisms underlying MC4R signaling, and development of new therapeutic agents. Understanding the interaction between MC4R and other genetic and environmental factors will be key to advancing both the prevention and treatment of obesity.

Comparative analysis of the human microbiome from four different regions of China and machine learning-based geographical inference.

The human microbiome, the community of microorganisms that reside on and inside the human body, is critically important for health and disease. However, it is influenced by various factors and may vary among individuals residing in distinct geographic regions. In this study, 220 samples, consisting of sterile swabs from palmar skin and oral and nasal cavities were collected from Chinese Han individuals living in Shanghai, Chifeng, Kunming, and Urumqi, representing the geographic regions of east, northeast, southwest, and northwest China. The full-length 16S rRNA gene of the microbiota in each sample was sequenced using the PacBio single-molecule real-time sequencing platform, followed by clustering the sequences into operational taxonomic units (OTUs). The analysis revealed significant differences in microbial communities among the four regions. Cutibacterium was the most abundant bacterium in palmar samples from Shanghai and Kunming, Psychrobacter in Chifeng samples, and Psychrobacillus in Urumqi samples. Additionally, Streptococcus and Staphylococcus were the dominant bacteria in the oral and nasal cavities. Individuals from the four regions could be distinguished and predicted based on a model constructed using the random forest algorithm, with the predictive effect of palmar microbiota being better than that of oral and nasal cavities. The prediction accuracy using hypervariable regions (V3-V4 and V4-V5) was comparable with that of using the entire 16S rRNA. Overall, our study highlights the distinctiveness of the human microbiome in individuals living in these four regions. Furthermore, the microbiome can serve as a biomarker for geographic origin inference, which has immense application value in forensic science.IMPORTANCEMicrobial communities in human hosts play a significant role in health and disease, varying in species, quantity, and composition due to factors such as gender, ethnicity, health status, lifestyle, and living environment. The characteristics of microbial composition at various body sites of individuals from different regions remain largely unexplored. This study utilized single-molecule real-time sequencing technology to detect the entire 16S rRNA gene of bacteria residing in the palmar skin, oral, and nasal cavities of Han individuals from four regions in China. The composition and structure of the bacteria at these three body sites were well characterized and found to differ regionally. The results elucidate the differences in bacterial communities colonizing these body sites across different regions and reveal the influence of geographical factors on human bacteria. These findings not only contribute to a deeper understanding of the diversity and geographical distribution of human bacteria but also enrich the microbiome data of the Asian population for further studies.

The influence of post-glacial migration and hybridization on the gene pool of marginal Quercus pubescens populations in Central Europe.

In Central Europe, the drought-tolerant downy oak (Quercus pubescens) is at the northern edge of its natural distribution range, often growing in small and spatially isolated populations. Here, we elucidate how the population genetic structure of Central European Q. pubescens was shaped by geographic barriers, genetic drift and introgression with the closely related sessile oak (Q. petraea). 27 Q. pubescens populations from the northern margin of Q. pubescens' natural distribution range were sampled. Based on 16 nuclear microsatellite markers (nSSRs), Bayesian clustering and distance-based analyses were performed to determine the intraspecific genetic structure and to identify genetic barriers. To identify drivers of introgression with Q. petraea, generalised linear models were applied to link levels of introgression with environmental conditions. To track post-glacial migration routes, the spatial distribution of haplotypes based on 8 chloroplast microsatellite markers (cpSSRs) was investigated. Based on nSSRs, the study populations of Q. pubescens were divided into a western and an eastern genetic cluster. Within these clusters, more pronounced genetic substructure was observed in the west, probably due to a rugged topography and limited gene flow. Introgression from Q. petraea was more prevalent at wetter and north-exposed sites and in the west. The identified cpSSR haplotypes followed known migration pathways. Our results suggest two late-glacial refugia in or near the southwestern Alps and the southeastern Alps as potential sources for post-glacial migration. Although some genetic exchange is evident in Northern Italy, south of the Alps, the two clusters remain distinct at a large scale. Landscape features and introgression with Q. petraea shaped the genetic substructure at a smaller scale. Our study provides a comprehensive overview of the genetic structure of Q. pubescens in Central Europe, relevant for conservation.

Analysis of exonic deletions in a large population study provides novel insights into NRXN1 pathology

The NRXN1 locus is a hotspot for non-recurrent copy number variants and exon-disrupting NRXN1 deletions have been associated with increased risk of neurodevelopmental disorders in case-control studies. However, corresponding population-based estimates of prevalence and disease-associated risk are currently lacking. Also, most studies have not differentiated between deletions affecting exons of different NRXN1 splice variants nor considered intronic deletions. We used the iPSYCH2015 case-cohort sample to obtain unbiased estimates of the prevalence of NRXN1 deletions and their associated risk of autism, schizophrenia, depression, and ADHD. Most exon-disrupting deletions affected exons specific to the alpha isoform, and almost half of the non-exonic deletions represented a previously reported segregating founder deletion. Carriage of exon-disrupting NRXN1 deletions was associated with a threefold and twofold increased risk of autism and ADHD, respectively, whereas no significantly increased risk of depression or schizophrenia was observed. Our results highlight the importance of using population-based samples in genetic association studies.

Congenital heart disease and arrhythmia disorders in newborns with congenital diaphragmatic hernia: a 23-year experience at a UK university pediatric surgical centre

PurposeCongenital diaphragmatic hernia (CDH) is associated with congenital heart disease (CHD) and index newborns reportedly may experience cardiac arrhythmia disorders [Tella et al.—Pediatric Critical Care Medicine 2022]. This study analyses, details and reports contemporary outcome metrics of CHD and cardiac rhythm disease (CRD) in CDH babies attending a university surgical centre.MethodsRetrospective analysis of medical records of all newborns undergoing Bochdalek CDH repair between 1999 and 2021 at a university paediatric surgical centre. CDH newborns with CHD and neonatal arrythmias were identified from echocardiogram and electrocardiogram (ECG) investigative studies. Operative native diaphragm and / or use of patch repair(s) was documented. Outcome(s) measured—(i) mortality and (ii) cardiopulmonary interventions including ventilatory strategies—ECMO (%), inotropes and anti-arrhythmic therapy(s).ResultsOf 173 CDH neonates, 95 (55%) had CHD of which 9 babies (10%) had cardiac arrhythmias. CDH and co-existing CHD was linked with (a) lower infant birth weights (3130 g vs 3357 g, p = 0.05), (b) increased use of inotrope agents (48.4% vs 39.3%, p = 0.03) and (c) greater use of high-frequency oscillatory ventilation (38.9% vs 23%, p = 0.004). CDH babies experiencing arrythmias were at higher risk (%) of developing pulmonary hypertension (66.7% vs 28.7%, p = 0.01). No significant differences were observed in ECMO utilisation (12% vs 6%, p = 0.46) or patch repair(s) (53% vs 46%, p = 0.06) in CDH patients with and without CHD. CHD was not associated with increased risk(s) of mortality (OR 2.58, 95% CI 0.81–8.24, p = 0.11). Of 9 index CDH patients with arrhythmias—4 babies (44%) required interventional treatments.ConclusionCHD was prevalent in a high percentage (%) of CDH newborns treated at this university centre and associated with increased use (%) of cardiovascular respiratory support including patch repair. A minority of patients (2.3%) had cardiac rhythm disorders requiring treatment(s). In those developing arrhythmias pulmonary hypertension may be a risk-linked event. Optimising outcomes to offset pulmonary hypertension requires further appraisal. Future large-scale population studies may help underscore the ‘real apparent incidence’ of cardiac rhythm disorders in CDH.

Population Studies and Molecular Mechanisms of Human Radioadaptive Capabilities: Is It Time to Rethink Radiation Safety Standards?

The evolution of man on Earth took place under conditions of constant exposure to background ionizing radiation (IR). From this point of view, it would be reasonable to hypothesize the existence of adaptive mechanisms that enable the human organism to safely interact with IR at levels approximating long-term natural background levels. In some situations, the successful operation of molecular mechanisms of protection against IR is observed at values significantly exceeding the natural background level, for example, in cancer cells. In 15–25% of cancer patients, cancer cells develop a phenotype that is resistant to high doses of IR. While further investigations are warranted, the current evidence suggests a strong probability of observing positive health effects, including an increased lifespan, a reduced cancer risk, and a decreased incidence of congenital pathologies, precisely at low doses of ionizing radiation. This review offers arguments primarily based on a phenomenological approach and critically reconsidering existing methodologies for assessing the biological risks of IR to human health. Currently, in the most economically developed countries, there are radiation safety rules that interpret low-dose radiation as a clearly negative environmental factor. Nowadays, this approach may pose significant challenges to the advancement of radiomedicine and introduce complexities in the regulation of IR sources. The review also examines molecular mechanisms that may play a key role in the formation of the positive effects of low-dose IR on human radioadaptive capabilities.

Treatment Advances in Perinatal Depression: Innovations and Promising Approaches

Background/Objectives: Psychotherapy and antidepressants are the standard treatment for depression during pregnancy or postpartum. However, several new treatments for depression represent major advances and paradigm changes. This commentary highlights some innovative treatment options that are on the horizon. Most of these modalities are promising, and most are non-invasive. Many of these modalities have been used in the general population, where evidence supports their use. The methods have only recently been used for pregnant and postpartum women. Other modalities are specifically for perinatal women but do not have an established track record. Methods: This commentary describes some promising approaches to treatment, while acknowledging that the literature is preliminary. The goal is to highlight some interesting approaches drawn from a recent comprehensive review of the entire literature on treatment for perinatal mental illness. Results: Integrative treatments include vitamin D, infant massage, mindfulness-based cognitive therapy, acupuncture, and repetitive transcranial magnetic stimulation (rTMS). Many studies in the general population have found that these methods are effective, and they also show promise for perinatal women without side effects associated with medications. Some of these treatments can also be adjuncts to what is considered standard care. Two new medications, brexanolone and esketamine, quickly and effectively treat severe depression and work on GABA and glutamate receptors rather than serotonin or norepinephrine. These medications become less effective after 30 days but can be combined with selective serotonin reuptake inhibitors (SSRIs). Conclusions: Pregnant and postpartum women seeking care for depression and other mental health conditions have many options beyond psychotherapy and SSRI/SNRI antidepressants. These modalities can also be added to their care.

Exploring the potential of Braingame Brian for executive function improvement in Spanish-speaking children with ADHD: A pilot study

ABSTRACT Considering the implications of executive function (EF) in the core symptoms of attention deficit hyperactivity disorder (ADHD), further research is required on strategies such as therapies, treatments, and rehabilitation programs focused on improving EF. This study aimed to assess the potential of an EF training program called “Braingame Brian” in improving working memory, inhibition, and cognitive flexibility in children with ADHD. The programme was developed in the Netherlands and has been shown to be effective in pilot studies of ADHD populations conducted in this country. However, it has not been used before in the Spanish-speaking population. A total of 41 children (aged 8–12 years) were assigned to the EF training or waitlist control groups. The intervention consisted of a 25-session training programme of approximately 45 min per day for nine consecutive weeks. Treatment outcomes were assessed using cognitive tasks of the trained EF, as well as evaluations of EF behaviors by parents and teachers. The initial findings suggest that the implementation of the Braingame Brian programme may be associated with improvements in working memory, inhibition, and cognitive flexibility. These preliminary results also indicate the potential for enhancements in parents’ and teachers’ perceptions of EF difficulties in children with ADHD.

Gripping insights: prevalence of hypertension and its association with relative muscle strength—a cross-sectional study in an adult Indian population

BackgroundHypertension and muscle strength are known to be associated; however, identifying simple clinical indicators of this relationship is challenging. Relative muscle strength (RMS), defined as strength per unit muscle mass, has been proposed as a potential indicator, but its association with hypertension is unclear. This study aimed to estimate the prevalence of hypertension and determine its association with RMS in an adult Indian population attending a tertiary care center in Gujarat.MethodsThis hospital-based cross-sectional study included 430 adults aged 18 years and older who were admitted to outpatient medicine clinics between January and October 2023. Grip strength and appendicular lean muscle mass (ALM), estimated using a validated formula, were measured. The RMS was calculated as grip strength/ALM. Hypertension was defined using standard criteria. Logistic regression was used to analyze the association between RMS (analyzed continuously and categorically in tertiles) and hypertension, adjusting for confounders. A p value of < 0.05 was considered significant.ResultsThe prevalence of prehypertension and hypertension was 187 (43%) and 96 (23%), respectively. Compared to participants in the low RMS tertile (0.00–2.45 kg/kg ALM), those in the high tertile (3.79–6.12 kg/kg ALM) had 26% lower odds of hypertension (OR 0.74, 95% CI 0.59–0.89) and 33% lower odds of prehypertension (OR 0.67, 95% CI 0.49–0.91) after adjusting for confounders. The RMS also showed strong negative correlations with systolic and diastolic blood pressure (r = − 0.559 and − 0.418, respectively; p < 0.001).ConclusionIncreased RMS was significantly protective against prehypertension and hypertension. These findings highlight the potential importance of muscle quality, beyond muscle mass, in blood pressure regulation.

The Local Ultraviolet to Infrared Treasury. I. Survey Overview of the Broadband Imaging

The Local Ultraviolet to Infrared Treasury (LUVIT) is a Hubble Space Telescope program that combines newly acquired data in the near-ultraviolet (NUV), optical, and near-infrared (NIR) with archival optical and NIR imaging to produce multiband panchromatic resolved stellar catalogs for 23 pointings in 22 low-mass, star-forming galaxies ranging in distance from the outskirts of the Local Group to ∼3.8 Mpc. We describe the survey design, detail the LUVIT broadband filter observations and the archival data sets included in the LUVIT reductions, and summarize the simultaneous multiband data reduction steps. The spatial distributions and color–magnitude diagrams (CMDs) from the resulting stellar catalogs are presented for each target, from the NUV to the NIR. We demonstrate in which regions of the CMDs stars with NUV and optical, optical and NIR, and NUV through NIR detections reside. For each target, we use the results from artificial star tests to measure representative completeness, bias, and total photometric uncertainty as a function of magnitude in each broadband filter. We also assess which LUVIT targets have significant spatial variation in the fraction of stars recovered at a given magnitude. The panchromatic LUVIT stellar catalogs will provide a rich legacy data set for a host of resolved stellar population studies.

Investigating the reasons behind a later or missed diagnosis of attention‐deficit/hyperactivity disorder in young people: A population cohort study

AbstractBackgroundAttention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition, more often diagnosed in males. In many individuals, particularly females, ADHD is diagnosed later or missed, the reasons for this are not fully understood. Timely diagnosis is needed to provide support, management, and treatment to improve outcomes. This study aimed to understand why some young people with ADHD experience later or missed diagnosis and to consider sex differences.MethodsThis study included 9991 (females = 43.69%) individuals from the Millenium Cohort Study, a UK based population study which defined recognised ADHD by a parent‐reported clinician diagnosis, and unrecognised ADHD by parent‐reported questionnaires. Behavioural and emotional difficulties, engagement in leisure activities, and parental characteristics, were compared between those recognised earlier (by ages 5/7, n = 264, f = 19.3%) versus later (by ages 11/14, n = 260, f = 21.2%), and those recognised (n = 524, f = 20.2%) versus unrecognised (n = 1,138, f = 38.7%) using logistic regression, with odds ratios (OR) and 95% confidence intervals (CI) analysed. Sex differences were investigated with an interaction analysis.ResultsThose recognised with ADHD earlier had more peer, conduct, and emotional problems, emotional dysregulation, lower cognitive ability, and poorer prosocial skills compared with those recognised later, ORs ranged from 0.27 (95% CI = 018, 0.41) to 1.20 (95% CI = 1.20, 1.32). Similar findings were seen when comparing those with recognised and unrecognised ADHD; ORs ranged from 0.11 (95% CI = 0.09, 0.15) to 1.31 (95% CI = 1.19, 1.43). Additionally, those recognised were more likely to have diagnosed autism and have less reported physical activity. Sex stratification showed that recognised males had higher emotional dysregulation than unrecognised males, but this was not seen in females.ConclusionsOur findings highlight the need to consider ADHD referral, regardless of cognitive and prosocial ability or comorbidities, if children are displaying ADHD symptoms. Additionally, symptoms of ADHD not traditionally included in screening criteria, such as emotional dysregulation, should be considered to improve gender‐inclusive recognition of ADHD.

Discourse theory and the turn to practice

Abstract This introductory article to the special issue on Discourse Theory and the Turn to Practice, takes the questions and tensions identified through the intensive study of populism as starting point for reflections on Discourse Theory as a framework for the study of political practice more broadly. Its aims are partly organizational and partly agenda-setting. Organizationally, it draws together major discussions and developments in Discourse Theory over the last ten years or so, especially those produced through an engagement with populism. Building on this, it points toward new frontiers for the development of Discourse Theory, organized around three dimensions of what could be called a ‘turn to practice’: (i) beyond ontology, (ii) beyond language, and (iii) beyond populism and (antagonistic) politics. After discussing how each of them play out in the study of populism, the article reflects on what taking seriously such a ‘turn to practice’ would mean for DT.

The Gut–Heart Axis: Effects of Intestinal Microbiome Modulation on Cardiovascular Disease—Ready for Therapeutic Interventions?

Recent reports demonstrate an association between distinct bacteria or bacteria-derived metabolites originating from the gut microbiome and the onset or progression of cardiovascular disease (CVD). This raises the opportunity to modulate the gut microbiome to prevent or treat CVD. To investigate whether intestinal microbiome modulation can prevent or treat CVD, this systematic literature review includes all randomized clinical trials on microbiome modulation and its effects on CVD risk published between August 2018 and August 2023. Within this review, we report the modulation of the gut microbiome by a variety of interventions and their effects on CVD, focusing on cardiovascular risk factors and risk markers of CVD. Beneficial effects were observed upon lifestyle intervention and probiotics use. The most promising diets for reducing risk factors of CVD were the Mediterranean diet, high-fiber diets, polyphenol-rich diets, and diets containing polyunsaturated fatty acids. Among drug interventions, only empagliflozin showed beneficial effects on CVD risk factors. Many dietary interventions were less conclusive because of the heterogeneity of study populations, small sample sizes, and short intervention windows or follow-up. Diet, lifestyle, probiotics, or drug interventions can modulate the gut microbiome and decrease risk markers or risk factors related to CVD. Yet, their effects on clinical endpoints remain to be determined.

Identification of adipose tissue-derived exosomal microRNA as a novel causal biomarker for cognitive impairment in type 2 diabetes mellitus: Triangulating evidence from Mendelian randomization and multicentre population studies.

To explore serum exosomal microRNAs (miRNAs) as risk biomarkers for early detection of cognitive impairment in type 2 diabetes mellitus (T2DM) patients. This study included two phases: a discovery phase and a validation phase. To detect adipose tissue exosomal biomarkers for T2DM patients, small RNA sequencing was conducted on a discovery population consisting of six T2DM patients and five subjects with normal glucose tolerance. To identify miRNAs with causal effects on cognitive impairment, Mendelian randomization (MR) analysis using publicly available genome wide association studies (GWAS) datasets was performed. Relationships between serum exosomal miRNAs and cognitive impairment were evaluated in a training population of 207 T2DM patients, and further validated in an external population of 101 T2DM patients from multiple centres. In the discovery phase, 13 exosomal miRNAs were significantly upregulated in adipose tissue of T2DM patients. MR analyses identified that increased miR-125a-5p was causally associated with increased Alzheimer's disease (AD) risk (OR = 1.231, 95% CI 1.062-1.426). In the validation phase, higher serum exosomal miR-125a-5p levels were related to increased amnestic mild cognitive impairment (aMCI) risk (OR = 1.066, 95% CI 1.030-1.103) and reduced left hippocampal body volume (r = -0.189, p < 0.05), achieving an area under the curve (AUC) of 0.728 for identifying aMCI in T2DM patients. External validation confirmed a diagnostic AUC of 0.738. Serum exosomal miR-125a-5p derived from adipose tissue can serve as a causal biomarker for cognitive impairment in T2DM patients.

Urinary Metabolite Profiles of Participants with Overweight and Obesity Prescribed a Weight Loss High Fruit and Vegetable Diet: A Single Arm Intervention Study

Background/Objectives: Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescribed a high F and V diet (7 servings daily). Methods: Adults with overweight and obesity (n = 34) received medical nutrition therapy counselling to increase their F and V intakes to national targets (7 servings a day). Data collection included weight, dietary intake, and urine samples at baseline at week 2 and week 10. Urinary metabolite profiles were quantified using 1H NMR spectroscopy. Machine learning statistical approaches were employed to identify novel urine-based metabolite biomarkers associated with high F and V diet patterns at weeks 2 and 10. Metabolic changes appearing in urine in response to diet were quantified using Metabolite Set Enrichment Analysis (MSEA). Results: Energy intake was significantly lower (p = 0.02) at week 10 compared with baseline. Total F and V intake was significantly higher at week 2 and week 10 (p &lt; 0.05). In total, 123 urinary metabolites were quantified. At week 10, 21 metabolites showed significant changes relative to baseline. Of these, 11 metabolites also significantly changed at week 2. These overlapping metabolites were acetic acid, dimethylamine, choline, fumaric acid, glutamic acid, L-tyrosine, histidine, succinic acid, uracil, histamine, and 2-hydroxyglutarate. Ridge Classifier and Linear Discriminant Analysis provided best prediction accuracy values of 0.96 when metabolite level of baseline was compared to week 10. Conclusions: Urinary metabolites quantified represent potential candidate biomarkers of high F and V intake, associated with a reduction in energy intake. Further studies are needed to validate these findings in larger population studies.

Gestational Diabetes Mellitus Prevalence and Risk Factors - A Study from a Tertiary Care Centre in North India

Introduction: Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) pose significant global health challenges. The increasing global prevalence of GDM and its associated complications underscores the need for proactive screening and management. The study aimed to evaluate the prevalence of GDM and its associated risk factors in a tertiary care hospital in North India Methodology: A prospective cross-sectional study conducted at Max Super Speciality Hospital, New Delhi, during 2016-2017, enrolled 900 pregnant women (aged 18-50 years) from the antenatal outpatient department (OPD). Primary objective: To assess impaired oral glucose tolerance prevalence (IADPSG criteria) at 24th-28th weeks. The data covered demographic, socioeconomic, obstetric, and medical details. Descriptive statistics were used to summarize the variables. Chi-square or Fisher's tests were applied to categorical data, while continuous data were analysed using independent t-tests. Multiple regression analysis was conducted to identify risk factors. Results: GDM was diagnosed in 7.4% of participants. Prevalence was highest in the age group &gt;35 years (36.2%, p=0.000), and a significant association was found between increasing body mass index (BMI) and GDM (p=0.04). Adverse obstetric history, including previous abortions and GDM in prior pregnancies, increased the risk of GDM. Complications during pregnancy, such as macrosomia (present in 1 patient with GDM and none in non-GDM), foetal distress (9.09% in GDM), and preeclampsia (4.7% in GDM), were higher in women with GDM. Vaginal delivery prevalence was higher in non-GDM, while GDM had a higher rate of caesarean section delivery (p&lt;0.005). Conclusion: The study discloses a 7.4% GDM prevalence in North Indian tertiary care, accentuating rising diabetes trends. Identified risk factors inform antenatal screening, highlighting the need for early GDM management to mitigate complications and prevent future diabetes. Single-centre limitations emphasise the necessity for broader population studies for accurate prevalence rates.

Etiology of prostate cancer with the TMPRSS2:ERG fusion: A systematic review of risk factors.

The most common somatic alteration in primary prostate cancer is the TMPRSS2:ERG gene fusion, which may be caused or promoted by distinct etiologic factors. The objective of this systematic review was to assess epidemiologic evidence on etiologic factors for prostate cancer by tumor TMPRSS2:ERG fusion status in human populations. Of 3071 publications identified, 19 cohort or case-control studies from six distinct study populations were included in this systematic review. Etiologic factors included germline genetic variants, circulating hormones, and dietary and lifestyle factors. Taller height, higher total and free testosterone levels, and fewer trinucleotide repeats in AR were possibly associated with higher risk of TMPRSS2:ERG-positive prostate cancer. Excess body weight, greater vigorous physical activity, higher lycopene intake, and the use of calcium channel blockers were associated with lower risk of TMPRSS2:ERG-positive prostate cancer. Diabetes and family history of prostate cancer were associated with both TMPRSS2:ERG-positive and TMPRSS2:ERG-negative prostate cancer. Prostate cancer germline variants had suggestive differential associations with TMPRSS2:ERG-positive or TMPRSS2:ERG-negative prostate cancer. However, results were based on few distinct study populations and generally had low precision, underscoring the need for replication. In conclusion, prostate cancer with TMPRSS2:ERG fusion is an etiologically distinct subtype that may be, in part, preventable by addressing modifiable and hormonally acting etiologic factors that align with the established mechanistic role of TMPRSS2:ERG in androgen, insulin, antioxidant, and growth factor pathways.

Association Between Melanoma Metastasis and Metabolic Syndrome: A Cross-Sectional Study in a Chinese Population.

Metabolic syndrome (MetS) remains a significant global public health concern. However, the relationship between MetS, its individual components and melanoma metastasis remains unexplored. We analysed the clinical data of 258 Chinese melanoma patients who had not undergo systemic therapy. Binary logistic regression, adjusted for sex and age, was employed to evaluate the connection between MetS and its components and melanoma metastasis. Of the 258 melanoma patients, 92 met the MetS criteria upon diagnosis. No direct association between MetS and melanoma metastasis was identified. However, specific components of MetS, namely low HDL-cholesterol levels (OR = 2.85, 95% CI:1.50-5.41, p < 0.05) and dysglycaemia (OR = 4.23, 95% CI:1.80-8.96, p < 0.05), were associated with melanoma metastasis. In subgroup analysis, hypertriglyceridemia correlated with melanoma metastasis in non-elderly patients (< 65 years) (OR = 2.69, 95% CI: 1.14-6.33, p < 0.05). Central obesity and hypertension showed no association. A dose-response analysis further indicated that melanoma metastasis risk escalated with increasing fasting blood glucose and blood triglyceride concentrations, and with decreasing blood HDL concentration. Our results suggest that monitoring and managing individual components of the MetS, particularly HDL-cholesterol levels, fasting glucose and triglyceride levels, may have potential prognostic benefits for melanoma in the Chinese population.

Transethnic analysis identifies SORL1 variants and haplotypes protective against Alzheimer's disease.

The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse. Logistic regression identified AD-associated SORL1 haplotypes in East Asian (N=5249) and European (N=8588) populations. Association analysis between SORL1 haplotypes and AD-associated traits or plasma biomarkers was conducted. The effects of non-synonymous mutations were assessed in cell-based systems. Protective SORL1 variants/haplotypes were identified in the East Asian and European populations. Haplotype Hap_A showed a strong protective effect against AD in East Asians, linked to less severe AD phenotypes, higher SORL1 transcript levels, and plasma proteomic changes. A missense variant within Hap_A, rs2282647-C allele, was linked to a lower risk of AD and decreased expression of a truncated SORL1 protein isoform. Our transethnic analysis revealed key SORL1 haplotypes that exert protective effects against AD, suggesting mechanisms of the protective role of SORL1 in AD. We examined the AD-protective mechanisms of SORL1 in the general population across diverse ancestral backgrounds by jointly analyzing data from three East Asian cohorts (ie, mainland China, Hong Kong, and Japan) and a European cohort. Comparative analysis unveiled key ethnic-specific SORL1 genetic variants and haplotypes. Among these, the SORL1 minor haplotype, Hap_A, emerged as the primary AD-protective factor in East Asians. Hap_A exerts significant AD-protective effects in both APOE ε4 carriers and non-carriers. SORL1 haplotype Hap_A is associated with cognitive function, brain volume, and the activity of specific neuronal and immune-related pathways closely connected to AD risk. Protective variants within Hap_A are linked to increased SORL1 expression in human tissues. We identified an isoform-specific missense variant in Hap_A that modifies the function and levels of a truncated SORL1 protein isoform that is poorly investigated.