AIMS: To identify the transcriptome expression profiles of peripheral blood mononuclear cells (PBMCs) in women with PCOS and controls. To investigate noninvasive diagnostic biomarkers and potential treatment targets to improve women's fertility.
METHODS: RNA sequencing (RNA-Seq) was conducted on PBMC samples from six patients with PCOS and six healthy controls. qRT-PCR validation was carried out in 68 subjects. Multivariate logistic regression was performed to assess the combined impact of biomarkers.
RESULTS: A total of 186 differentially expressed genes (DEG) were found between patients and controls (log2FC >1, p < 0.05). Enrichment analysis revealed cytokine-mediated signaling pathways, cytokine activity, and cytokine-cytokine receptor interaction. RNA sequencing showed consistency with qRT-PCR. Women with PCOS had significantly higher levels of AQP9 (p < 0.001), PROK2 (p = 0.001), and S100A12 (p < 0.001) expression compared to controls. AQP9 (AUC = 0.77), PROK2 (AUC = 0.71), and S100A12 (AUC = 0.82) adequately discriminated women with PCOS from healthy controls. In addition, multiple logistic regression on biomarkers resulted in a significant diagnostic power with an AUC = 0.89, 95 % CI: 0.81-0.97, p < 0.0001. Further associations were analyzed between relative gene expression and clinical, anthropometric, hormonal, and ultrasonographic data.
CONCLUSIONS: Dysregulated RNA expression in PBMCs may contribute to an increased risk of PCOS and serve as a potential diagnostic biomarker. The involvement of inflammatory and cytokine-related pathways supports the notion that PCOS is a chronic inflammatory condition.
METHODS: Analytical studies describing the vancomycin levels of vancomycin-sensitive enterococcal infections among adult population were searched. The primary outcome was 30-day all-cause mortality, and the secondary outcomes were clinical failure and nephrotoxicity. Study characteristics were extracted and pooled using random-effects meta-analysis. The study quality was assessed using the Joanna Briggs Institute critical appraisal tool.
RESULTS: A total of nine retrospective cohorts studies involving 1013 patients with vancomycin-sensitive enterococci were included. The meta-analysis found that high area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of vancomycin ≥ 389 mg*h/L significantly lowered the 30-day mortality (odds ratio [OR], 0.44, 95% confidence interval [CI], 0.26-0.75). Analysis of the target AUC/MIC showed that high vancomycin AUC/MIC (≥ 389-400 mg*h/L) significantly reduced clinical failure rate (OR 0.59, 95% CI 0.37-0.94). The mortality and treatment failure rates did not differ significantly between those with high or low trough levels. Higher vancomycin AUC/MIC and trough levels were significantly associated with increased nephrotoxicity (OR 3.11, 95% CI 1.65-5.89; OR 2.95, 95% CI 1.60-5.44, respectively).
CONCLUSIONS: The use of a higher vancomycin AUC/MIC concentration can be effective to reduce 30-day mortality and clinical failure but this needs to take into consideration the risk of nephrotoxicity. Well-conducted prospective studies are warranted due to the scarcity of evidence.
METHODS: This study utilized cross-sectional data from the 2017 China General Social Survey (N = 2195). We employed the Ordered Probit (O-Probit) model and ordinary least squares regression to examine the impact of digital skills on health and explore the underlying mechanisms. Health inequalities across different groups were measured using the health concentration index.
RESULTS: Enhancing digital skills enhances population health by boosting economic status, increasing social participation, and improving access to information. However, the impact varies by age and residence. Digital skills have a stronger effect on the health of young and middle-aged individuals, as well as urban residents, compared to older adults and rural populations. Furthermore, digital skills exacerbate health inequalities, benefiting high-income groups and widening the gap between income levels.
CONCLUSIONS: Widespread promotion and continuous improvement of digital skills are key to enhancing public health. We need to focus on the popularization of digital skills and the construction of digital infrastructure for low-income disadvantaged groups and rural areas, as well as use various means to reduce group and regional differences in the impact of digital skills on health conditions.
METHODS: A cross-sectional study was conducted between February 1 and March 31, 2024, with 370 pregnant women recruited through convenience sampling. Inclusion criteria were Malaysian citizenship, age above 18 years, and ability to read and comprehend Malay. Data collection involved self-reported sociodemographic questionnaires, the Edinburgh Postnatal Depression Scale (EPDS), and the WHO Multicountry Study on Women's Health and Life Events Questionnaire.
RESULTS: The prevalence of antenatal depression was 8.4%. IPV was reported by 64.1% of participants, with 54.6% experiencing controlling behavior, 30.0% emotional violence, 2.4% physical violence, and 3.5% sexual violence. Bivariate analysis showed that emotional violence (p < 0.001), physical violence (p < 0.001), sexual violence (p < 0.001), and hospitalization (p = 0.006) were significantly associated with an increased risk of antenatal depression. Multivariable logistic regression revealed that women receiving outpatient care had significantly lower odds of developing antenatal depression compared to hospitalized women (adjusted OR 0.262, 95% CI 0.100-0.683; p = 0.006). Women who experienced sexual violence were 18 times more likely to develop antenatal depression (adjusted OR 18.761, 95% CI 3.603-97.684; p < 0.001).
CONCLUSION: The study highlights the need for healthcare workers to recognize risk factors for antenatal depression, particularly IPV.
METHODS: Criteria were set for categorisation of patients as moderate or severe based on resource utilisation. The two methods used for cost computation were (1) cost estimation based on predefined clinical pathways for case management (2) computation of actual costs using patient-level data from retrospective review of all AHT admissions in 2021. Both methods utilised a combination of activity-based and top-down costing according to availability of reference data. Costs are presented in USD.
RESULTS: Costs for 9 severe and 3 moderate cases in 2021 amounted to $70,532.16, of which 93 % was for severe cases. Cost estimate for moderate cases was $2009.88 while actual costs ranged between $749.37-3115.47 (median $1422.76). Cost estimates of $15,125.76-$17,958.18 for severe cases exceeded actual costs of $2195.57-$13,186.03 (median $7379.40) for severe cases due to shorter-than-expected duration of stay, with only 2 who underwent neurosurgical procedures. Major cost contributors were duration of stay, intensive care, ventilation and neurosurgical procedures.
CONCLUSION: Cost comparison utilising predefined treatment standards versus actual patient data which reveals major cost determinants enables refinement of budget allocation. Median medical costs for severe cases which exceeded the monthly income ceilings of low- and middle-income households in Malaysia demonstrate the economic burden of AHT, reinforcing the need to invest in prevention.
METHODS: A cluster-randomized controlled trial was conducted with 180 participants from 12 schools, randomly assigned to intervention or control groups. The intervention group participated in a 90-minute educational session, with follow-up assessments at baseline, and at 1, 3, and 6 months' post-intervention, using validated Arabic questionnaires. Data analysis was performed using SPSS version 22.0, with Generalized Estimating Equations (GEE) applied to assess differences within and between groups over time. Statistical significance was set at P
METHODS AND RESULTS: This study investigates the effect of overexpressing the rice HKT1;5 gene in Arabidopsis thaliana on its tolerance to salinity and drought. The OsHKT1;5 gene was introduced into Arabidopsis under the control of 35 S promoter of CaMV via floral dip transformation method. PCR confirmed the integration of the transgene into the Arabidopsis genome, while qPCR analysis showed its expression. Three transgenic lines of OsHKT1;5 were used for stress treatment and phenotypic studies. The overexpressed lines showed considerably higher germination rates, increased leaf counts, greater fresh and dry weights of the roots and shoots, higher chlorophyll contents, longer root lengths, and reduced Na+ levels together with increased K+ ions levels after salt and drought treatments, in comparison to wild-type plants. Furthermore, overexpressed lines exhibited higher antioxidant levels than wild-type plants under salinity and drought conditions. In addition, transgenic lines showed higher expression levels of the OsHKT1;5 gene in both roots and shoots compared to wild-type plants.
CONCLUSIONS: In conclusion, this study revealed OsHKT1;5 as a promising candidate for enhancing tolerance to salinity and drought stresses in rice, marking a significant step toward developing a new rice variety with improved abiotic stress tolerance.
METHODS: We developed a comprehensive framework for forecasting life expectancy, healthy life expectancy (HALE), cause-specific mortality, and disability-adjusted life-years (DALYs) due to 359 causes of disease and injury burden from 2022 to 2050 for the USA and all 50 states and Washington, DC. Using the GBD 2021 Future Health Scenarios modelling framework, we forecasted drivers of disease, demographic drivers, risk factors, temperature and particulate matter, mortality and years of life lost (YLL), population, and non-fatal burden. In addition to a reference scenario (representing the most probable future trajectory), we explored various future scenarios and their potential impacts over the next several decades on human health. These alternative scenarios comprised four risk elimination scenarios (including safer environment, improved behavioural and metabolic risks, improved childhood nutrition and vaccination, and a combined scenario) and three USA-specific scenarios based on risk exposure or attributable burden in the best-performing US states (improved high adult BMI and high fasting plasma glucose [FPG], improved smoking, and improved drug use [encompassing opioids, cocaine, amphetamine, and others]).
FINDINGS: Life expectancy in the USA is projected to increase from 78·3 years (95% uncertainty interval 78·1-78·5) in 2022 to 79·9 years (79·5-80·2) in 2035, and to 80·4 years (79·8-81·0) in 2050 for all sexes combined. This increase is forecasted to be modest compared with that in other countries around the world, resulting in the USA declining in global rank over the 2022-50 forecasted period among the 204 countries and territories in GBD, from 49th to 66th. There is projected to be a decline in female life expectancy in West Virginia between 1990 and 2050, and little change in Arkansas and Oklahoma. Additionally, after 2023, we projected almost no change in female life expectancy in many states, notably in Oklahoma, South Dakota, Utah, Iowa, Maine, and Wisconsin. Female HALE is projected to decline between 1990 and 2050 in 20 states and to remain unchanged in three others. Drug use disorders and low back pain are projected to be the leading Level 3 causes of age-standardised DALYs in 2050. The age-standardised DALY rate due to drug use disorders is projected to increase considerably between 2022 and 2050 (19·5% [6·9-34·1]). Our combined risk elimination scenario shows that the USA could gain 3·8 additional years (3·6-4·0) of life expectancy and 4·1 additional years (3·9-4·3) of HALE in 2050 versus the reference scenario. Using our USA-specific scenarios, we forecasted that the USA could gain 0·4 additional years (0·3-0·6) of life expectancy and 0·6 additional years (0·5-0·8) of HALE in 2050 under the improved drug use scenario relative to the reference scenario. Life expectancy and HALE are likewise projected to be 0·4-0·5 years higher in 2050 under the improved adult BMI and FPG and improved smoking scenarios compared with the reference scenario. However, the increases in these scenarios would not substantially improve the USA's global ranking in 2050 (from 66th of 204 in life expectancy in the reference scenario to 63rd-64th in each of the three USA-specific scenarios), indicating that the USA's best-performing states are still lagging behind other countries in their rank throughout the forecasted period. Regardless, an estimated 12·4 million (11·3-13·5) deaths could be averted between 2022 and 2050 if the USA were to follow the combined scenario trajectory rather than the reference scenario. There would also be 1·4 million (0·7-2·2) fewer deaths over the 28-year forecasted period with improved adult BMI and FPG, 2·1 million (1·3-2·9) fewer deaths with improved exposure to smoking, and 1·2 million (0·9-1·5) fewer deaths with lower rates of drug use deaths.
INTERPRETATION: Our findings highlight the alarming trajectory of health challenges in the USA, which, if left unaddressed, could lead to a reversal of the health progress made over the past three decades for some US states and a decline in global health standing for all states. The evidence from our alternative scenarios along with other published studies suggests that through collaborative, evidence-based strategies, there are opportunities to change the trajectory of health outcomes in the USA, such as by investing in scientific innovation, health-care access, preventive health care, risk exposure reduction, and education. Our forecasts clearly show that the time to act is now, as the future of the country's health and wellbeing-as well as its prosperity and leadership position in science and innovation-are at stake.
FUNDING: Bill & Melinda Gates Foundation.