Nevin Manimala

Mol Neurodegener. 2024 May 18;19(1):41. doi: 10.1186/s13024-024-00727-7.

ABSTRACT

Recent evidence suggests that Alzheimer’s disease (AD) genetic risk variants (rs1582763 and rs6591561) of the MS4A locus are genome-wide significant regulators of soluble TREM2 levels such that the minor allele of the protective variant (rs1582763) is associated with higher sTREM2 and lower AD risk while the minor allele of (rs6591561) relates to lower sTREM2 and higher AD risk. Our group previously found that higher sTREM2 relates to higher Aβ₄₀, worse blood-brain barrier (BBB) integrity (measured with the CSF/plasma albumin ratio), and higher CSF tau, suggesting strong associations with amyloid abundance and both BBB and neurodegeneration complicate interpretation. We expand on this work by leveraging these common variants as genetic tools to tune the interpretation of high CSF sTREM2, and by exploring the potential modifying role of these variants on the well-established associations between CSF sTREM2 as well as TREM2 transcript levels in the brain with AD neuropathology. Biomarker analyses leveraged data from the Vanderbilt Memory & Aging Project (n = 127, age = 72 ± 6.43) and were replicated in the Alzheimer’s Disease Neuroimaging Initiative (n = 399, age = 73 ± 7.39). Autopsy analyses were performed leveraging data from the Religious Orders Study and Rush Memory and Aging Project (n = 577, age = 89 ± 6.46). We found that the protective variant rs1582763 attenuated the association between CSF sTREM2 and Aβ₄₀ (β = -0.44, p-value = 0.017) and replicated this interaction in ADNI (β = -0.27, p = 0.017). We did not observe this same interaction effect between TREM2 mRNA levels and Aβ peptides in brain (Aβ total β = -0.14, p = 0.629; Aβ_1-38, β = 0.11, p = 0.200). In contrast to the effects on Aβ, the minor allele of this same variant seemed to enhance the association with blood-brain barrier dysfunction (β = 7.0e-4, p = 0.009), suggesting that elevated sTREM2 may carry a much different interpretation in carriers vs. non-carriers of this allele. When evaluating the risk variant (rs6591561) across datasets, we did not observe a statistically significant interaction against any outcome in VMAP and observed opposing directions of associations in ADNI and ROS/MAP on Aβ levels. Together, our results suggest that the protective effect of rs1582763 may act by decoupling the associations between sTREM2 and amyloid abundance, providing important mechanistic insight into sTREM2 changes and highlighting the need to incorporate genetic context into the analysis of sTREM2 levels, particularly if leveraged as a clinical biomarker of disease in the future.

PMID:38760857 | DOI:10.1186/s13024-024-00727-7

Reprod Health. 2024 May 17;21(1):65. doi: 10.1186/s12978-024-01796-z.

ABSTRACT

BACKGROUND: Low use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use.

METHODS: We analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand.

RESULTS: There were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (± 8) years, and 17.3% (n = 591) were living with HIV. Overall, 43.9% (n = 1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR] = 1.14; 95% confidence interval [95%CI]: 1.02-1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR = 0.80; 95%CI = 0.70-0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant.

CONCLUSIONS: Unsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.

PMID:38760855 | DOI:10.1186/s12978-024-01796-z

Hum Genomics. 2024 May 17;18(1):47. doi: 10.1186/s40246-024-00621-9.

ABSTRACT

Association between genomic variants and athletic performance has seen a high degree of controversy, as there is often conflicting data as far as the association of genomic variants with endurance, speed and strength is concerned. Here, findings from a thorough meta-analysis from 4228 articles exploring the association of genomic variants with athletic performance in power and endurance sports are summarized, aiming to confirm or overrule the association of genetic variants with athletic performance of all types. From the 4228 articles, only 107 were eligible for further analysis, including 37 different genes. From these, there were 21 articles for the ACE gene, 29 articles for the ACTN3 gene and 8 articles for both the ACE and ACTN3 genes, including 54,382 subjects in total, from which 11,501 were endurance and power athletes and 42,881 control subjects. These data show that there is no statistically significant association between genomic variants and athletic performance either for endurance or power sports, underlying the fact that it is highly risky and even unethical to make such genetic testing services for athletic performance available to the general public. Overall, a strict regulatory monitoring should be exercised by health and other legislative authorities to protect the public from such services from an emerging discipline that still lacks the necessary scientific evidence and subsequent regulatory approval.

PMID:38760851 | DOI:10.1186/s40246-024-00621-9

J Occup Med Toxicol. 2024 May 17;19(1):19. doi: 10.1186/s12995-024-00419-4.

ABSTRACT

BACKGROUND: Employees in social work exhibit high rates of sick leave due to mental health issues. Additionally, work-related demands in youth welfare have increased in recent years. Particularly in light of the escalating shortage of skilled professionals in this field, this trend becomes especially critical. The aim of this study is to systematically examine health-relevant working conditions, coping strategies, and health indicators in youth welfare. A special focus is placed on a differentiated analysis of job-related characteristics in the context of outpatient and residential youth welfare.

METHODS: Mean values, standard deviations and the reliability of scales are measured. In addition to descriptive statistics, t-tests for analyzing mean differences, as well as correlation analyses and odds ratios as measures of association, are computed.

RESULTS: A total of N = 1044 employees in youth welfare participated in the online survey. Among them, 671 individuals belonged to the field of residential youth welfare, and 373 to outpatient youth welfare. The results indicate that, in youth welfare in general, a variety of emotional, social, qualitative, and quantitative demands exhibit high levels. The comparison between outpatient and residential youth welfare reveals differences in half of the demands. The significant differences are observed for social demands and aggression from clients, which are statistically significant higher in the residential setting. Regarding resources, the most significant difference is observed for autonomy, which is higher in the outpatient setting. Overall, the association patterns reveals more similarities than differences between outpatient and residential settings. In both settings working conditions seem to have deteriorated during the pandemic.

CONCLUSIONS: In conclusion, the identified job-related characteristics in outpatient and residential youth welfare exhibit more similarities than differences. Nevertheless, the identified differences provide insights into the specific features of each work context, offering valuable starting points for targeted health promotion in practice.

TRIAL REGISTRATION: This trial is recorded at the Hamburg University Ethics Committee (AZ 2022_027).

PMID:38760845 | DOI:10.1186/s12995-024-00419-4

Genome Biol. 2024 May 17;25(1):124. doi: 10.1186/s13059-024-03254-2.

ABSTRACT

Single-cell CRISPR screens (perturb-seq) link genetic perturbations to phenotypic changes in individual cells. The most fundamental task in perturb-seq analysis is to test for association between a perturbation and a count outcome, such as gene expression. We conduct the first-ever comprehensive benchmarking study of association testing methods for low multiplicity-of-infection (MOI) perturb-seq data, finding that existing methods produce excess false positives. We conduct an extensive empirical investigation of the data, identifying three core analysis challenges: sparsity, confounding, and model misspecification. Finally, we develop an association testing method – SCEPTRE low-MOI – that resolves these analysis challenges and demonstrates improved calibration and power.

PMID:38760839 | DOI:10.1186/s13059-024-03254-2

J Ovarian Res. 2024 May 17;17(1):103. doi: 10.1186/s13048-024-01425-0.

ABSTRACT

BACKGROUND: Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that can help predicting which FMR1 premutation women will develop FXPOI. We previously demonstrated that high FMR4 levels can discriminate between FMR1 premutation carriers with and without FXPOI. In the present study the relationship between the expression levels of FMR4 and the ovarian reserve markers was assessed in female FMR1 premutation carriers under age of 35 years.

METHODS: We examined the association between FMR4 transcript levels and the measures of total antral follicle count (AFC) and serum anti-müllerian hormone (AMH) levels as markers of ovarian follicle reserve.

RESULTS: Results revealed a negative association between FMR4 levels and AMH (r = 0.45) and AFC (r = 0.64). Statistically significant higher FMR4 transcript levels were found among those FMR1 premutation women with both, low AFCs and AMH levels.

CONCLUSIONS: These findings reinforce previous studies supporting the association between high levels of FMR4 and the risk of developing FXPOI in FMR1 premutation carriers.

PMID:38760837 | DOI:10.1186/s13048-024-01425-0

Nutr J. 2024 May 17;23(1):52. doi: 10.1186/s12937-024-00950-4.

ABSTRACT

BACKGROUND: Changes in economy and dietary guidelines brought a great shock to diet quality and meal behaviors, but if these transformations have extended to minerals intake and their sources was still poorly understood. It is essential to evaluate time trends in minerals intake and their sources to inform policy makers.

OBJECTIVE: To investigate trends in minerals intake and their sources among U.S. adults.

METHODS: This analysis used dietary data collected by 24-h recalls from U.S. adults (≥ 20 years) in NHANES (1999-March 2020). Minerals intake, age-adjusted percentage of participants meeting recommendations, and minerals sources were calculated among all participants and by population subgroups in each NHANES survey cycle. Weighted linear or logistic regression models were used to examine the statistical significance of time trends.

RESULTS: A total of 48223 U.S. adults were included in this analysis. From 1999 to March 2020, intake of calcium (from 0.94 to 1.02 g/day), magnesium (from 308.07 to 321.85 mg/day), phosphorus (from 1.24 to 1.30 g/day), and sodium (from 3.24 to 3.26 mg/day) from food and beverages (FB) and dietary supplements (DSs) significantly increased, and intake of iron (from 19.17 to 16.38 mg/day), zinc (from 16.45 to 14.19 mg/day), copper (from 1.79 to 1.38 mg/day), and potassium (from 2.65 to 2.50 g/day) from FB + DSs decreased (all FDR < 0.05). Additionally, age-adjusted percentage of participants meeting recommendations for calcium, phosphorus, sodium, and selenium significantly increased, that for iron, potassium, zinc, and copper decreased (all FDR < 0.05). Minerals intake and time trends in minerals intake were highly variable depending on age, gender, race/ethnicity, education, and income. For example, white, higher socioeconomic status participants had a higher minerals intake (e.g. iron, zinc, and copper), but had a greater decrease in minerals intake. Furthermore, the percentage of minerals from milks and DSs decreased, and that from beverages increased.

CONCLUSION: From 1999 to March 2020, both minerals intake and their sources experienced a significant alteration among U.S. adults. Many differences in minerals intake and their food sources across sociodemographic characteristics appeared to narrow over time. Although some improvements were observed, important challenges, such as overconsumption of sodium and underconsumption of potassium, calcium, and magnesium, still remained among U.S. adults.

PMID:38760828 | DOI:10.1186/s12937-024-00950-4

Int J Equity Health. 2024 May 17;23(1):100. doi: 10.1186/s12939-024-02192-6.

ABSTRACT

BACKGROUND: Young people (aged 10 to 24 years) in sub-Saharan Africa bear a huge and disproportionate burden of poor sexual and reproductive health (SRH) outcomes due to inequalities and discrimination in accessing sexual and reproductive health services (SRHS). This study assessed the experiences and perceptions of discrimination among young people seeking SRH services in Primary Health Centers (PHCs) using an intersectionality lens.

METHODS: A cross-sectional mixed-methods study was undertaken in six local government areas (LGAs) in Ebonyi State, southeast Nigeria. The LGAs comprise both urban and rural locations. The study population for the quantitative survey consisted of 1025 randomly selected young boys and girls aged 15-24 years. Eleven focus group discussions (FGDs) were conducted with the young people. Descriptive and inferential analyses were performed for quantitative data, while thematic analysis was performed for the qualitative data, using NVivo.

RESULTS: A total of 16.68% participants in the survey reported that young girls/women were treated badly/unfairly compared to young boys/men when seeking SRH services in PHCs; 15.22% reported that young clients get treated badly/unfairly from adults; and 12.49% reported that young clients with poor economic status were treated unfairly. Respondents also reported that young clients with disability (12.12%), and those who are poorly educated or uneducated (10.63%) are treated badly by healthcare providers when they access SRH services. Young people in urban areas were about 7 times more likely to believe that girls/young women are treated badly than boys/young men when seeking SRH services in PHCs compared to those who live in rural areas (p < 0.001). Among the young girls/women, residing in urban areas, being poor and in school increased the likelihood of getting treated badly/unfairly when receiving SRH services by 4 times (p < 0.001). The qualitative results revealed that health workers were generally harsh to young people seeking SRH services and the level of harshness or unfriendliness of the health workers varied depending on the young person’s social identity.

CONCLUSION: There are varieties of intersecting factors that contribute to the discrimination of young clients in PHCs. This underscores the urgent need to prioritize intersectional perspectives in the design and implementation of interventions that will improve access and use of SRH services by young people.

PMID:38760811 | DOI:10.1186/s12939-024-02192-6

Arch Public Health. 2024 May 17;82(1):73. doi: 10.1186/s13690-024-01247-y.

ABSTRACT

BACKGROUND: A significant factor impacting the incidence of maternal and neonatal fatalities is the timely initiation of antenatal care (ANC) services in healthcare facilities. Despite the recommendations by the World Health Organization and the numerous benefits of timely initiation of ANC, studies have revealed that the overall prevalence of timely ANC initiation in 36 sub-Saharan African countries remains low and women in The Gambia also initiate ANC late. However, no known study in The Gambia has focused on assessing the factors associated with timely initiation of ANC at the time of writing this paper. Thus, this study aimed to assess the prevalence and factors associated with the timely initiation of ANC among reproductive-age women in The Gambia.

METHODS: A cross-sectional survey design was used in this study and conducted among 5,734 reproductive-age women using data from the 2019-2020 Gambia Demographic and Health Survey (GDHS). Using STATA version 14.0, we conducted the analysis using descriptive and inferential statistics. Multilevel logistic regression models were fitted to determine the factors associated with timely ANC utilization and adjusted odds ratios were used to present the results with statistical significance set at p < 0.05.

RESULTS: The overall prevalence of timely initiation of ANC services among reproductive-age women in The Gambia was 43.0%. We found that women aged 30-34 [aOR = 1.79, 95% CI = 1.30-2.47], those who were married [aOR = 2.69, 95% CI = 1.85-3.90] as well as women from the richest households [aOR = 1.63, 95% CI = 1.20, 2.20] had higher odds of seeking timely ANC services as compared to their counterparts. Also, those who had given birth to two children [aOR = 0.74, 95% CI = 0.6 -0.91] had lower odds of initiating timely ANC as compared to those who had given birth only once. Women who reside in rural areas [aOR = 1.72, 95%CI = 1.34, 2.20] also had higher odds of seeking timely ANC services than those residing in urban areas.

CONCLUSION: Individual-level factors such as maternal age, marital status, parity, wealth status, place of residence, and religion were associated with the timely initiation of ANC services among reproductive-age women. These factors ought to be considered in efforts to increase the timely initiation of ANC among reproductive-age women in The Gambia.

PMID:38760806 | DOI:10.1186/s13690-024-01247-y

BMC Nephrol. 2024 May 17;25(1):167. doi: 10.1186/s12882-024-03602-1.

ABSTRACT

INTRODUCTION: Acute kidney injury (AKI) is associated with increased risk of heart failure (HF). Determining the type of HF experienced by AKI survivors (heart failure with preserved or reduced ejection fraction, HFpEF or HFrEF) could suggest potential mechanisms underlying the association and opportunities for improving post-AKI care.

METHODS: In this retrospective study of adults within the Vanderbilt University health system with a diagnosis of HF, we tested whether AKI events in the two years preceding incident HF associated more with HFpEF or HFrEF while controlling for known predictors. HF outcomes were defined by administrative codes and classified as HFpEF or HFrEF by echocardiogram data. We used multivariable logistic regression models to estimate the effects of AKI on the odds of incident HFpEF versus HFrEF.

RESULTS: AKI (all stages) trended towards a preferential association with HFpEF in adjusted analyses (adjusted OR 0.80, 95% CI 0.63 – 1.01). Stage 1 AKI was associated with higher odds of HFpEF that was statistically significant (adjusted OR 0.62, 95% CI 0.43 – 0.88), whereas stages 2-3 AKI showed a trend toward HFrEF that did not reach statistical significance (adjusted OR 1.11, 95% CI 0.76 – 1.63).

CONCLUSIONS: AKI as a binary outcome trended towards a preferential association with HFpEF. Stage 1 AKI was associated with higher odds of HFpEF, whereas stage 2-3 trended towards an association with HFrEF that did not meet statistical significance. Different mechanisms may predominate in incident HF following mild versus more severe AKI. Close follow-up with particular attention to volume status and cardiac function after discharge is warranted after even mild AKI.

PMID:38760794 | DOI:10.1186/s12882-024-03602-1