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Genetic examination for fetuses with increased nuchal translucency by exome sequencing

J Obstet Gynaecol Res. 2022 Oct 30. doi: 10.1111/jog.15482. Online ahead of print.

ABSTRACT

AIM: This retrospective study aimed to investigate the value of exome sequencing (ES) in fetuses with isolated first-trimester increased nuchal translucency (NT) and normal chromosomes.

METHODS: ES was performed on 103 fetuses with isolated first trimester increased NT and normal chromosomes. The detection rate of monogenic conditions was analyzed.

RESULTS: Diagnostic variants were detected in nine cases in which phenotypes and genotypes correlated well, two positive cases were Thanatophoric dysplasia type I, and one case was Kabuki syndrome, which had been detected in previous studies. Eight of the nine cases with diagnostic variants developed additional structural malformations later in pregnancy. Among the nine positive cases, six had a NT thickness between 95th percentile (95th-3.4 mm), and three cases with an increased NT of 3.5 mm or greater. Also, there was no statistical difference in the diagnosis of diagnostic variants in cases with or without a thickened nuchal fold (NF).

CONCLUSIONS: The diagnostic yield of prenatal ES is low for fetuses with an isolated increased NT. In addition to Noonan syndrome, there are additional genetic syndromes such as Kabuki syndrome and Thanatophoric dysplasia type I that are potentially associated with an increased NT. A cut-off of greater than the 95th percentile may be useful in case selection for ES. Whether it is clinically meaningful to monitor NF values for fetuses with isolated increased NT and normal chromosomes worth considering.

PMID:36310088 | DOI:10.1111/jog.15482

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Association between Dietary Protein Intake and Type 2 Diabetes Mellitus in Chinese Rural Elderly Population: A Matched Case-Control Study

J Nutr Sci Vitaminol (Tokyo). 2022;68(5):399-408. doi: 10.3177/jnsv.68.399.

ABSTRACT

The purpose of this study was to examine the association between dietary protein intake and the risk of type 2 diabetes mellitus (T2DM) among a Chinese rural elderly population. We used the demographic and dietary information of adults over age 65 in the Henan Rural Cohort Study to identify and pair 950 T2DM patients with healthy controls in a 1 : 1 matched case-control study. Dietary data was collected through a Food Frequency Questionnaire. A multivariate logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of T2DM risk according to protein intake. After adjustment for confounding factors, higher intake of total protein was negatively associated with T2DM risk in the total population (extreme-tertile OR=0.75, 95% CI: 0.58-0.93) and women (extreme-tertile OR=0.84, 95% CI: 0.47-0.93). Multivariate-adjusted ORs for the risk of T2DM in the highest compared with lowest tertile of plant protein intake in the total population and in women were 0.86 (95% CI: 0.60-0.84) and 0.58 (95% CI: 0.36-0.95), respectively. Our results suggest that the protein intake, especially plant protein, has a significant association with the risk of T2DM in rural elderly populations, and the sources of protein may be also important in future guidelines.

PMID:36310074 | DOI:10.3177/jnsv.68.399

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Effect of Vitamin D3 Supplementation on Interleukin 6 and C-Reactive Protein Profile in Athletes

J Nutr Sci Vitaminol (Tokyo). 2022;68(5):359-367. doi: 10.3177/jnsv.68.359.

ABSTRACT

Vitamin D3 has a preventive, anti-inflammatory effect. However, there are still few studies linking the effects of athlete training to vitamin D3 supplementation and the immune response. The study evaluated the impact of vitamin D3 supplementation on interleukin 6 (IL-6) release during physical exercise in relation to C-reactive protein (CRP) levels in healthy male athletes. Twenty-five soccer players were divided into two groups-with (GS) and without (GN) vitamin D3 supplementation in a dose of 20,000 IU twice a week for 8 wk (about 6,000 IU/d). At the baseline (T1) and at the end (T2) of the training cycle serum concentrations of 25-hydroxyvitamin D [25(OH)D], IL-6 and CRP were measured. In the GS group, we observed a significant increase in 25(OH)D concentration (p=0.004), and non-significantly increased levels (p>0.05) of IL-6 and CRP. At the baseline, CRP in the supplemented athletes who had suboptimal vitamin D3 concentration in T1 (GSO) was significantly higher than in those with an optimal baseline vitamin D3 level (GO) (p=0.028). However, in GO in T2, a non-significant trend of negative correlation (p=0.055) between 25(OH)D concentration and IL-6 level was found. In the total study group (TG), a statistically significant (p=0.021) negative correlation in T1 was observed between 25(OH)D and CRP. However, our results do not support the immune-modulatory effect of vitamin D3 supplementation in a dose of 6,000 IU/d in athletes, in relation to IL-6 production and its subsequent stimulatory effect on CRP releasing.

PMID:36310069 | DOI:10.3177/jnsv.68.359

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Body Composition Assessment by Dual-Energy X-Ray Absorptiometry: A Useful Tool for the Diagnosis of Lipedema

Obes Facts. 2022 Oct 28:1-12. doi: 10.1159/000527138. Online ahead of print.

ABSTRACT

INTRODUCTION: Lipedema is a poorly known condition. Diagnosis is based almost exclusively on clinical criteria, which may be subjective and not always reliable. This study aimed to investigate regional body composition (BC) by dual-energy X-ray absorptiometry (DXA) in patients with lipedema and healthy controls and to determine cut-off values of fat mass (FM) indices to provide an additional tool for the diagnosis and staging of this condition.

METHODS: This study is a single-center case-control study performed at Lausanne University Hospital, Switzerland. Women with clinically diagnosed lipedema underwent regional BC assessment by DXA. The control group without clinical lipedema was matched for age and body mass index (BMI) at a ratio of 1:2 and underwent similar examination. Regional FM (legs, arms, legs and arms, trunk, android and gynoid FM) was measured in (kg) and divided by FM index (FMI) (kg/m2) and total FM (kg). The trunk/legs and android/gynoid ratios were calculated. For all indices of FM distribution showing a significant difference between cases and controls, we defined the receiver operating characteristic (ROC) curves, calculating the area under the curve (AUC), sensitivity, specificity, and Youden’s index. Types and stages of lipedema were compared in terms of FM indices. Correlation analyses between all FM distribution indices and lipedema stages were performed.

RESULTS: We included 222 women (74 with lipedema and 148 controls). Overall, the mean age was 41 years (standard deviation [SD] 11), and mean BMI was 30.9 kg/m2 (SD 7.6). A statistically significant difference was observed for all DXA-derived indices of FM distribution between groups, except for arm FM indices. The ROC curve analysis of leg FM/total FM, as a potential indicator of lipedema, resulted in an AUC of 0.90 (95% confidence interval 0.86-0.94). According to Youden’s index, optimal cut-off value identifying lipedema was 0.384. Sensitivity and specificity were 0.95 and 0.73, respectively. We found no significant differences between lipedema types and stages in terms of FM indices, nor significant correlations between the latter and lipedema stages.

DISCUSSION/CONCLUSION: BC assessment by DXA, and particularly calculation of the leg FM/total FM index, is a simple tool that may help clinicians rule out lipedema in doubtful cases.

PMID:36310013 | DOI:10.1159/000527138

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Circulatory disease mortality among male medical radiation workers in South Korea, 1996-2019

Scand J Work Environ Health. 2022 Oct 30:4066. doi: 10.5271/sjweh.4066. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the relationship between occupational radiation exposure and circulatory disease (CD) mortality among medical radiation workers.

METHODS: The study included 53 860 male diagnostic medical radiation workers enrolled in the National Dosimetry Registry (NDR) between 1996 and 2011 in South Korea. NDR data were linked with mortality data obtained from the national registry at the end of 2019. Observed CD mortality rates in this population were compared to those in the general population using the standardized mortality ratio (SMR). The relative risk (RR) for occupational history was estimated by use of internal comparisons, and the excess relative risk (ERR) was used to quantify the radiation dose-response relationship.

RESULTS: A total of 320 deaths due to CD were identified among 53 860 male medical radiation workers. The SMR of CD was significantly lower among male workers than the general population. A linear dose-response model provided an estimated ERR per 100 mGy for CD [0.85, 95% confidence interval (CI) -0.11-1.82], ischemic heart disease (1.18, 95% CI -0.69-3.05), and cerebrovascular disease (0.23, 95% CI -0.48-0.94) with a 10-years lag, showing no statistical evidence of a radiation dose-response relationship. Additional adjustments for non-radiation factors did not affect the findings on occupational radiation risk for CD mortality. Sensitivity analyses excluding workers employed <1 year or who had exposure to a cumulative badge dose of ≥1 mSv showed similar results.

CONCLUSIONS: Occupational radiation doses were non-significantly positively associated with CD mortality among male diagnostic medical radiation workers. However, cautious interpretation is needed due to the limitations of short follow-up.

PMID:36309988 | DOI:10.5271/sjweh.4066

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Steroid injections in musculoskeletal conditions and COVID infection rates: What is the impact on positive rates following the injection?

Musculoskeletal Care. 2022 Oct 30. doi: 10.1002/msc.1707. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Therapeutic glucocorticosteroid injections are commonly utilised to manage musculoskeletal (MSK) complaints. Following the SARS-CoV-2 pandemic, national guidelines advised against their use due to potential immunosuppressant effects. The aim of the study was to determine whether steroid injections for MSK conditions impacts on positive COVID 19 infection rates.

PATIENTS AND METHODS: This retrospective evaluation involved primary care participants who received a steroid injection for a MSK condition. 291 participants receiving a total of 299 steroid injections entered the study between the 25 September 2020 and the 29 April 2021.

RESULTS: Six participants had positive polymerase chain reaction (PCR) tests, averaging 22.83 days (SD 10.48) after the injection. An infection rate of 2.06% was demonstrated in the injection group with the control group demonstrating 6.97% (p = 0.000752) with statistical significance set at p = 0.05. The odds ratio was identified as 0.27 indicating a lower odds of a positive PCR test compared with the control group.

CONCLUSIONS: This retrospective evaluation found a low risk of positive PCR tests for low and moderate COVID-19 risk patients injected during the COVID-19 pandemic. Glucocorticosteroid injections within the COVID-19 pandemic were not associated with higher COVID-19 rates compared to the local population, in fact, they were related to lower rates. For future studies, large scale studies and meta analyses are needed to provide greater generalisation to the population.

PMID:36309979 | DOI:10.1002/msc.1707

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Population pharmacokinetic modeling of daridorexant, a novel dual orexin receptor antagonist

CPT Pharmacometrics Syst Pharmacol. 2022 Oct 30. doi: 10.1002/psp4.12877. Online ahead of print.

ABSTRACT

The analysis aimed at identifying subject-specific characteristics (covariates) influencing exposure to daridorexant and quantification of covariate effects to determine clinical relevance. Data from 13 Phase 1, 2 Phase 2, and 2 Phase 3 studies were pooled to develop a population pharmacokinetic model describing daridorexant concentration over time. Covariate effects were quantified based on model predictions. A two-compartment model with dose-dependent bioavailability, absorption lag time, linear absorption, and nonlinear elimination described the data best. Statistically significant covariates were food status on absorption (lag time and rate constant), time of drug administration (morning, bedtime) on absorption rate constant, lean body weight on central volume of distribution and elimination, fat mass on peripheral volume of distribution and intercompartmental drug transfer, and age and alkaline phosphatase on elimination. Age, lean body weight, fat mass, and alkaline phosphatase influence exposure (AUC, tmax , Cmax , and next-morning concentration) to a limited extent, i.e., less than 20% difference from a typical subject. Morning administration is not relevant for daridorexant use by insomnia patients. The food effect with simultaneous intake of high-fat high-calorie food is an extreme-case scenario unlikely to occur in clinical practice. Body composition, alkaline phosphatase, and age showed clinically negligible effects on exposure to daridorexant. Lean body weight and fat mass described the pharmacokinetics of daridorexant better than other body size descriptors (body weight, height, body mass index), suggesting a convenient physiological alternative to reduce the number of covariates in population pharmacokinetic models. The results indicate that differences between subjects do not require dose adjustments.

PMID:36309969 | DOI:10.1002/psp4.12877

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Differential response to the South American rice water weevil (Coleoptera: Curculionidae) damage of rice cultivars with contrasting levels of resistance: implications for field management

Pest Manag Sci. 2022 Oct 30. doi: 10.1002/ps.7262. Online ahead of print.

ABSTRACT

BACKGROUND: Oryzophagus oryzae (Costa Lima) (Coleoptera: Curculionidae) is a major pest of flooded rice paddies throughout South America, and species with very similar life histories are present in many rice-producing regions of the world (collectively referred to here as RWWs). The damage caused by RWW larvae on rice cultivars with contrasting levels of resistance (‘BRS Pampa CL’= “Pamp”: susceptible, ‘BRS Atalanta’= “Atal”: resistant-antibiosis) was evaluated in two consecutive years in the field under seven infestation levels: 0, 2, 4, 6, 8, 10, and 20 adult couples per cage with plants.

RESULTS: Higher densities of adults increased the number of leaf-feeding scars and larvae on roots, respectively, at the rate up to 2.14 and 2.75 in “Pamp” and 2.23 and 2.48 in “Atal”, with the total number of larvae generated being lower in “Atal”. Grain yield was negatively impacted with increasing larval density on the roots, mainly by decreasing root volume and the number of grains per panicle. Root injury intensity and yield loss showed a non-linear relationship. It was found that significant yield losses occurred from 8.37 larvae per plant in “Pamp” and 9.80 larvae per plant in “Atal”.

CONCLUSION: The results provided the first evidence of a tolerance limit for RWW larval damage that, even though similar between cultivars of contrasting resistance, corresponds to twice the current conventional level for larval control in Brazil. We also discuss here the potential of applying tolerance limits to manage the RWW adult population in rice fields. This article is protected by copyright. All rights reserved.

PMID:36309968 | DOI:10.1002/ps.7262

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Added prognostic value of molecular imaging parameters over proliferation index in typical lung carcinoid: an [18F]FDG PET/CT and SSTR imaging study

Ann Nucl Med. 2022 Oct 30. doi: 10.1007/s12149-022-01797-7. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was performed to evaluate the prognostic meaning of volumetric and semi-quantitative parameters measured using [18F]FDG PET/CT and somatostatin receptor (SSTR) imaging in patients with typical lung carcinoid (TC), and their relationship with proliferative index (Ki67).

METHODS: We retrospectively reviewed 67 patients (38-94 years old, mean: 69.7) with diagnosis of TC who underwent [18F]FDG PET/CT and/or SSTR scintigraphy/SPECT with [111In]DTPA-Octreotide plus contrast-enhanced CT (CECT) at staging evaluation. All patients had Ki67 measured and a follow-up (FU) of at least 1 year. SSTR density (SSTRd) was calculated as the percentage difference of tumor/non-tumor ratio at 4 and 24 h post-injection. At PET/CT, metabolic activity was measured using SUVmax and SUVratio; volumetric parameters included MTV and TLG of the primary tumor, measured using the threshold SUV41%. ROC analysis, discriminant analysis and Kaplan-Meier curves (KM) were performed.

RESULTS: 11 patients died during FU. Disease stage (localized versus advanced), SUVratio, SUVmax, Ki67, MTV and TLG were significantly higher in non-survivors than in survivors. ROC curves resulted statistically significant for Ki67, SUVratio, SUVmax, MTV and TLG. On multivariate analysis, stage of disease and TLG were significant independent predictors of overall survival (OS). In KM curves, the combination of disease stage and TLG identified four groups with significantly different outcomes (p < 0.005). Metabolic activity (SUVmax and SUVratio) was confirmed as significant independent prognostic factor for OS also in patients with advanced disease, with the best AUC using SUVmax. In patients with advanced and localized disease, SSTRd proved to be the best imaging prognostic factor for progression and for disease-free survival (DFS), respectively. In localized disease, SSTRd 31.5% identified two subgroups of patients with significant different DFS distribution and in advanced disease, a high cutoff value (58.5%) was a significant predictor of adverse prognosis.

CONCLUSION: Volumetric and semi-quantitative parameters measured using [18F]FDG PET/CT and SSTR imaging combined with Ki67 may provide a reference for prognosis evaluation of patients with TC, to better stratify risk groups with the goal of developing individualized therapeutic strategies.

PMID:36309948 | DOI:10.1007/s12149-022-01797-7

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Intersecting Relationships of Psychosocial and Structural Syndemic Problems Among People with HIV in South Africa: Using Network Analysis to Identify Influential Problems

AIDS Behav. 2022 Oct 30. doi: 10.1007/s10461-022-03906-z. Online ahead of print.

ABSTRACT

In South Africa, little is known about interrelationships between syndemic problems among people with HIV (PWH). A better understanding of syndemic problems may yield important information regarding factors amenable to mitigation. We surveyed 194 PWH in Khayelitsha, outside of Cape Town, South Africa. We used network analysis to examine the frequency of 10 syndemic problems and their interrelationships. Syndemic problems among PWH in South Africa were common; 159 (82.8%) participants reported at least 2 co-occurring syndemic problems and 90 (46.9%) endorsed 4 or more. Network analysis revealed seven statistically significant associations. The most central problems were depression, substance use, and food insecurity. Three clusters of syndemics were identified: mood and violence; structural factors; and behavioral factors. Depression, substance use, and food insecurity commonly co-occur among PWH in sub-Saharan Africa and interfere with HIV outcomes. Network analysis can identify intervention targets to potentially improve HIV treatment outcomes.

PMID:36309936 | DOI:10.1007/s10461-022-03906-z