Background and objectiveTo investigate the relationship between inflammation and hypertension by comparing epigenetic and serum biomarkers of inflammation and their association with target organ damage (TOD).MethodsThe epigenome-wide methylation profiles of peripheral leukocyte DNA from 176 patients with hypertension were analyzed using Illumina Infinium Methylation EPIC BeadChips. The commercially available Olink® Target 96 Inflammation panels were utilized to evaluate markers associated with inflammation. We identified CpG-protein association protein quantitative trait methylation loci (pQTMs) using mixed linear regression, adjusting for potential confounders. The possible roles of the discovered pQTMs were ascertained by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analyses. The association between pQTMs and TOD was also analyzed.ResultsIn our analysis, we found 771 significant associations across 11 biomarkers, with a false discovery rate (FDR) of less than 0.05. Lambda estimates ranged from 0.847 to 1.202. Among these, 39 pQTMs showed an association with urine albumin-creatinine ratio, while 82 pQTMs showed an association with carotid intima-media thickness.ConclusionOur findings contribute to the understanding of inflammatory biomarkers associated with alterations in DNA methylation in hypertension. However, these results will need to be validated in future studies.

Background Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally. Methods In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR. Results Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies ( I 2 = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients ( P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients ( P < 0.05). Conclusions Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.

BACKGROUND AND PURPOSE:CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. METHODS:The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeat-primed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. RESULTS:Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. CONCLUSIONS:Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Folate has antioxidant properties, and low concentration in seminal plasma may be associated with increased DNA damage in sperm. Mutations of the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes, including MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), and MTRR A66G (rs1801394), can lead to decreased activity of the encoded folate metabolic enzymes, thereby affecting male reproduction. The current SNP detection methods commonly used in clinical practice have some shortcomings, such as long time-consuming, complex detection steps, or high cost. The purpose of this study was to establish a simple, time-saving, sensitive, accurate, and easy to clinical popularization method for folate metabolism gene detection. We combined ARMS-PCR with TaqMan fluorescent probe to establish an ARMS TaqMan real-time PCR detection method. According to the variation of rs1801131, rs1801133, and rs1801394, two specific primers (one wild type and one mutant) were designed. Mismatched nucleotides were introduced at the penultimate or third position to improve the specificity of the primer. Specific TaqMan probe was introduced to detect PCR products to improve the sensitivity of the method. The results showed that the sensitivity of ARMS TaqMan real-time PCR in SNP genotyping was 1 ng, and the accuracy was 100%. A total of 249 clinical samples were detected by the established method, and the correlation between three SNPs and semen quality was analyzed. We found that individuals carrying the AG + GG genotype of rs1801394 had a lower risk of abnormal semen quality. In conclusion, we developed a highly sensitive, accurate, rapid, and easy to be popularized method for detecting SNPs of rs1801394, rs1801131, and rs1801133. ARMS TaqMan real-time PCR is a reliable SNP genotyping method in folate metabolism genes.

What is already known about this topic?:Vaginitis is a prevalent and treatable gynecological condition in women that is associated with adverse reproductive outcomes, human papillomavirus (HPV) infection, and elevated human immunodeficiency virus (HIV) transmission risk. What is added by this report?:This study identifies elevated infection risks among women aged 35-54 years, those with three or more pregnancies, and individuals who smoke or consume alcohol, with notably higher prevalence rates in Hubei and Yunnan Provinces. The findings demonstrate that awareness of cervical cancer screening serves as a protective factor, while emphasizing screening's crucial role in early vaginitis detection. What are the implications for public health practice?:Public health interventions should prioritize women aged 35-54 years, those with multiple pregnancies, and individuals engaging in high-risk behaviors. Enhancing cervical cancer screening awareness and accessibility is essential for improving early detection and management of vaginal infections, thereby reducing reproductive health disparities.

Objective To visualize the research status and hotspots of women's common disease screening based on CiteSpace 6.1.R6,and to provide a reference for the in-depth research in this field thereafter. Methods The relevant articles were retrieved from the China National Knowledge Infrastructure with the time interval from January 1,1992 to December 13,2022.The analysis was conducted on the number of annual publications,countries(regions),institutions,author collaboration networks,keyword co-occurrence,clustering,and bursts. Results A total of 900 papers that met the criteria were included,and the number of annual publications showed a trend of first increasing and then decreasing.The cross-institutional collaboration network was mature.The research hotspots mainly covered women's health,the prevalence of women's diseases,reproductive health,and breast diseases.The hotspots have evolved from an initial focus on reproductive health care to gynecological disease management,and eventually to reproductive health and holistic health care in women. Conclusions The attention should be kept on the screening of women's common diseases.It is advisable to synchronize the screening of women's common diseases with the screening of cervical and breast cancers to expand the screening coverage,promote early disease detection and treatment,and comprehensively safeguard women's health.

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Supplemental Table 3. Environmental Factors and colorectal cancer: associations by study design

Funding sources, acknowledgements, consortia involved in study and bioinformatics tools used

Provides an overview of the methods for each of the included studies

PDF file - 168K, SNP details by study.

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Contains more detailed information on the individual cohorts contributing to the study and their genotyping results; Supplemental Tables 1 and 2

INTRODUCTION/AIMS:Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy. METHODS:We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants. RESULTS:The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20. DISCUSSION:HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.

Supplementary Methods from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Table S2: Odds ratio and 95% confidence limits for cancers associated with variants with pleiotropic associations. Figure S1: Flowchart showing analysis steps. Figure S2. Manhattan plots by chromosome for individual cancer sites. Figure S3. Results for rs11571833. Figure S4: Conditional QQ-plots.

Supplemental Table S1. Food groupings used in the dietary pattern analysis. Supplemental Table S2. Comparisons of Cox proportional hazards regression model and competing risk model in associations between dietary patterns and prostate cancer-specific mortality among 926 men diagnosed with non-metastatic prostate cancer Supplemental Table S3. Relative risks between food groups with loading factor > 0.3 within each dietary pattern and prostate cancer-specific and all-cause mortality among men with non-metastatic prostate cancer (n=926)a.

PDF file - 67K, Descriptives for smoking, BMI, height, dietary variables, alcohol, sex, and NSAID use.

PDF file - 55K, Further information about main finding

Perspective on this Article from A Large Prospective Study of SEP15 Genetic Variation, Interaction with Plasma Selenium Levels, and Prostate Cancer Risk and Survival