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NPJ Genomic Medicine Jun 2024Leveraging whole genome sequencing data of 1751 individuals from the UK and 2587 Qatari subjects, we suggest here an association of rare variants mapping to the sour...
Leveraging whole genome sequencing data of 1751 individuals from the UK and 2587 Qatari subjects, we suggest here an association of rare variants mapping to the sour taste-associated gene KCNJ2 with reduced low-density lipoprotein cholesterol (LDL-C, P = 2.10 × 10) and with a 22% decreased dietary trans-fat intake. This study identifies a novel candidate rare locus for LDL-C, adding insights into the genetic architecture of a complex trait implicated in cardiovascular disease.
PubMed: 38942744
DOI: 10.1038/s41525-024-00417-9 -
Journal of Clinical Lipidology Apr 2024Heterozygous Familial Hypercholesterolemia (HeFH) is an autosomal dominant disorder causing elevated low density lipoprotein cholesterol (LDL-C) and premature...
Heterozygous Familial Hypercholesterolemia (HeFH) is an autosomal dominant disorder causing elevated low density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Universal cholesterol screening in childhood leads to children serving as the index case for their family, but efficacy of cascade screening and genetic counseling in this population is not well understood. The institutional pediatric lipid clinic database was queried from 2011 to 2022 for subjects <18 years who met clinical HeFH diagnostic criteria (N = 256). Median peak LDL-C was 198 mg/dL (IQR 179-238 mg/dL) and 69.5 % of subjects were the index case. The number of new HeFH cases identified per index case was 3.55 ± 1.87. Genetic counseling was offered to 38.7 % of subjects and genetic testing was completed by 10.9 %, 53.6 % of whom had a pathogenic or likely pathogenic genetic variant for HeFH. Our findings highlight the effectiveness of cascade screening from pediatric index cases identified through universal screening. However, genetic counseling and genetic testing may be underutilized in this population.
PubMed: 38942689
DOI: 10.1016/j.jacl.2024.04.127 -
The Science of the Total Environment Jun 2024Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists...
BACKGROUND
Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism.
METHODS
Plasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model.
RESULTS
Single-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDLC). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that SeFe exhibited synergistic effects on LDL-C and non-HDL-C, and SeSn showed a synergistic effect on HDLC.
CONCLUSIONS
Our study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects.
PubMed: 38942316
DOI: 10.1016/j.scitotenv.2024.174315 -
Forensic Science International Jun 2024We present an assessment of several geospatial layers proposed as models for detecting clandestine graves in Mexico. The analyses were based on adapting the classical...
We present an assessment of several geospatial layers proposed as models for detecting clandestine graves in Mexico. The analyses were based on adapting the classical ROC curves to geospatial data (gROC) using the fraction of the predicted area instead of the false positive rate. Grave locations were obtained for ten Mexican states that represent the most conflicting regions in Mexico, and 30 layers were computed to represent geospatial models for grave detection. The gROC analysis confirmed that the travel time from urban streets to grave locations was the most critical variable for detecting graves, followed by nighttime light brightness and population density, whereas, contrary to the rationale, a previously proposed visibility index is less correlated with grave locations. We were also able to deduce which variables are most relevant in each state and to determine optimal thresholds for the selected variables.
PubMed: 38941898
DOI: 10.1016/j.forsciint.2024.112114 -
JMIR Public Health and Surveillance Jun 2024Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given...
BACKGROUND
Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given this relationship, the concepts of metabolically healthy and unhealthy obesity, considering metabolic status, have been evolving. Attention is being directed to metabolically healthy people with obesity who have relatively low transition rates to noncommunicable diseases. As obesity rates continue to rise and unhealthy behaviors prevail among young adults, there is a growing need for obesity management that considers these metabolic statuses. A nomogram can be used as an effective tool to predict the risk of transitioning to metabolically unhealthy obesity from a metabolically healthy status.
OBJECTIVE
The study aimed to identify demographic factors, health behaviors, and 5 metabolic statuses related to the transition from metabolically healthy obesity to unhealthy obesity among people aged between 20 and 44 years and to develop a screening tool to predict this transition.
METHODS
This secondary analysis study used national health data from the National Health Insurance System in South Korea. We analyzed the customized data using SAS (SAS Institute Inc) and conducted logistic regression to identify factors related to the transition from metabolically healthy to unhealthy obesity. A nomogram was developed to predict the transition using the identified factors.
RESULTS
Among 3,351,989 people, there was a significant association between the transition from metabolically healthy to unhealthy obesity and general characteristics, health behaviors, and metabolic components. Male participants showed a 1.30 higher odds ratio for transitioning to metabolically unhealthy obesity than female participants, and people in the lowest economic status were also at risk for the transition (odds ratio 1.08, 95% CI 1.05-1.1). Smoking status, consuming >30 g of alcohol, and insufficient regular exercise were negatively associated with the transition. Each relevant variable was assigned a point value. When the nomogram total points reached 295, the shift from metabolically healthy to unhealthy obesity had a prediction rate of >50%.
CONCLUSIONS
This study identified key factors for young adults transitioning from healthy to unhealthy obesity, creating a predictive nomogram. This nomogram, including triglycerides, waist circumference, high-density lipoprotein-cholesterol, blood pressure, and fasting glucose, allows easy assessment of obesity risk even for the general population. This tool simplifies predictions amid rising obesity rates and interventions.
Topics: Humans; Republic of Korea; Male; Female; Adult; Young Adult; Obesity, Metabolically Benign; Metabolic Syndrome; Nomograms; Obesity; Health Behavior; Risk Factors
PubMed: 38941611
DOI: 10.2196/52103 -
Current Sports Medicine Reports Jul 2024Female wrestling has grown exponentially over the past decade. Within the United States, 46 states now recognize female high school wrestling, and 153 colleges have... (Review)
Review
Female wrestling has grown exponentially over the past decade. Within the United States, 46 states now recognize female high school wrestling, and 153 colleges have programs. It is on track to become an NCAA championship-level sport in 2026. A primary health and safety risk among this cohort pertains to rapid weight loss strategies. These can lead to intentional caloric restriction and decreased body fatness, with the perceived goal of attaining a competitive advantage. Low energy availability and low body fatness are associated with a number of health concerns including menstrual dysfunction and loss of bone mineral density in girls and women. The current recommendation of 12% as a minimum for percentage body fat is very likely too low, opening the door for health perturbations among this population. The minimum threshold might more appropriately fall within the range of 18% to 20%. Body fat assessment methods, primarily skinfold measures that are used to guide weight class selection, have not been adequately validated among this population and therefore should be an area of research focus, while also exploring alternative assessment techniques. Further, we recommend that weight cycling, restrictive energy intake, and intentional dehydration be avoided. Research should assess the effects of frequent weight cycling (to "make weight") and prolonged periods of low body fat on the reproductive and bone health of these athletes. Finally, research and clinical evaluations on female wrestlers are limited, and we offer a list of research priorities for future investigation into this contemporary issue.
Topics: Female; Humans; Bone Density; Menstruation Disturbances; Weight Loss; Wrestling
PubMed: 38941548
DOI: 10.1249/JSR.0000000000001183 -
Revista de La Facultad de Ciencias... Jun 2024Metabolic syndrome (MS) is associated with increased cardiovascular risk. Blood donors are an apparently healthy population in which certain cardiometabolic...
INTRODUCTION
Metabolic syndrome (MS) is associated with increased cardiovascular risk. Blood donors are an apparently healthy population in which certain cardiometabolic characteristics are not evaluated in their selection, and there is limited information on their presence.
AIM
To determine the frequency of metabolic syndrome and its metabolic characteristics in blood donors. Materials and methods: Cross-sectional study was carried in a population of 244 blood donors between 18 and 55 years of age who attended the Hemotherapy and Blood Bank Service of the Cayetano Heredia Hospital in Lima, Perú during the month of May 2023. The diagnosis of MS was made according to the Adult Treatment Panel III (ATP III) criteria. A bivariate analysis was performed between MS and metabolic characteristics with sex and a significance level of 5% was considered.
RESULTS
63.9% of blood donors were male. 43.6% of the population had MS. The most frequent characteristics found were hypertriglyceridemia (54.5%), abdominal obesity (51.2%) and high-density lipoprotein (HDL) low (48.8%). The age range of 40 to 49 years presented the highest frequency of MS (14.3%). Hypertriglyceridemia and high blood pressure were associated with male sex (p=0.003 and p=0.019 respectively), while low HDL was associated with female sex (p<0.001).
CONCLUSIONS
Blood donors present an elevated frequency of MS. The detection of MS in apparently healthy populations as part of primary care could allow the formulation of strategies for early detection of cardiovascular risk factors.
Topics: Humans; Metabolic Syndrome; Male; Female; Blood Donors; Adult; Cross-Sectional Studies; Middle Aged; Young Adult; Adolescent; Peru; Risk Factors; Obesity, Abdominal; Sex Factors; Sex Distribution
PubMed: 38941225
DOI: 10.31053/1853.0605.v81.n2.42446 -
JAMA Network Open Jun 2024While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain.
IMPORTANCE
While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain.
OBJECTIVE
To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction.
DESIGN, SETTING AND PARTICIPANTS
Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024.
MAIN OUTCOMES AND MEASURES
Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles.
RESULTS
A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk.
CONCLUSIONS AND RELEVANCE
In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.
Topics: Humans; Hip Fractures; Male; Female; Risk Assessment; Aged, 80 and over; Prospective Studies; Bone Density; Risk Factors; Femur Neck
PubMed: 38941095
DOI: 10.1001/jamanetworkopen.2024.18612 -
Human Psychopharmacology Jun 2024In this cross-sectional study, we compared fasting serum asprosin levels and metabolic parameters between patients receiving one of three atypical antipsychotics...
BACKGROUND
In this cross-sectional study, we compared fasting serum asprosin levels and metabolic parameters between patients receiving one of three atypical antipsychotics (olanzapine, risperidone, or aripiprazole) and healthy subjects.
METHODS
The study population included 62 adult outpatients with schizophrenia and 22 healthy controls, matched for age and gender. Patients were in remission and had been on stable monotherapy with one of these atypical antipsychotics for over 6 months. Body Mass Index (BMI) and fasting serum levels of asprosin, glucose, HA1c, insulin, and lipid profile were compared across the investigated groups. Additionally, the number of participants meeting the insulin resistance criterion, defined as homeostasis model assessment for insulin resistance (HOMA-IR) >2.5, as well as the number of participants with elevated BMI levels (men >27 kg/m, women >25 kg/m) were compared among the groups.
RESULTS
We observed statistically significant differences in BMI and fasting serum levels of glucose, HA1c, insulin, triglyceride (TG), high-density lipoprotein cholesterol, and asprosin among patients receiving olanzapine or risperidone, as compared to those receiving aripiprazole and healthy subjects. Patients on aripiprazole exhibited values comparable to healthy subjects, whereas those on risperidone or olanzapine showed significantly higher values, with the highest observed in the olanzapine group. Additionally, the prevalence of participants meeting the insulin resistance criterion and those with elevated BMI was also greater in individuals receiving olanzapine or risperidone compared to those on aripiprazole and healthy subjects. Serum asprosin levels showed a significant positive correlation with BMI and several metabolic parameters, including HbA1c, fasting insulin, HOMA-IR, and TG. No significant differences were observed among the investigated groups in terms of serum levels of total cholesterol and low-density lipoprotein cholesterol.
CONCLUSIONS
Our cross-sectional study highlights the association between elevated asprosin levels, weight gain, and metabolic disorders in patients treated with olanzapine and risperidone. Given the bidirectional nature of the relationship between serum asprosin levels and these metabolic disturbances, further research is warranted to elucidate potential causative pathways.
PubMed: 38940745
DOI: 10.1002/hup.2907 -
Chemical Science Jun 2024Study of alternating DNA GC sequences by different time-resolved spectroscopies has provided fundamental information on the interaction between UV light and DNA, a...
Study of alternating DNA GC sequences by different time-resolved spectroscopies has provided fundamental information on the interaction between UV light and DNA, a process of great biological importance. Multiple decay paths have been identified, but their interplay is still poorly understood. Here, we characterize the photophysics of GC-DNA by integrating different computational approaches, to study molecular models including up to 6 bases described at a full quantum mechanical level. Quantum dynamical simulations, exploiting a nonadiabatic linear vibronic coupling (LVC) model, coupled with molecular dynamics sampling of the initial structures of a (GC) DNA duplex, provide new insights into the photophysics in the sub-picosecond time-regime. They indicate a substantial population transfer, within 50 fs, from the spectroscopic states towards G → C charge transfer states involving two stacked bases (CT), thus explaining the ultrafast disappearance of fluorescence. This picture is consistent with that provided by quantum mechanical geometry optimizations, using time dependent-density functional theory and a polarizable continuum model, which we use to parametrize the LVC model and to map the main excited state deactivation pathways. For the first time, the infrared and excited state absorption signatures of the various states along these pathways are comprehensively mapped. The computational models suggest that the main deactivation pathways, which, according to experiment, lead to ground state recovery on the 10-50 ps time scale, involve CT followed by interstrand proton transfer from the neutral G to C. Our calculations indicate that CT is populated to a larger extent and more rapidly in GC than in CG steps and suggest the likely involvement of monomer-like and interstrand charge transfer decay routes for isolated and less stacked CG steps. These findings underscore the importance of the DNA sequence and thermal fluctuations for the dynamics. They will also aid the interpretation of experimental results on other sequences.
PubMed: 38939156
DOI: 10.1039/d4sc00910j