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: We investigated the interaction between these derivatives and the hCA II isozyme via various spectroscopic and docking methods.
RESULTS: The kinetic data demonstrates that compound 1 (C1) and compound 2 (C2) share a similar inhibitory strength against hCA II, effectively inhibiting its esterase activity through a noncompetitive mechanism with Ki values at low micromolar levels. Fluorescence measurements indicated that the synthesized compounds suppressed the inherent fluorescence of hCA II via a static quenching process, with each compound showing a singular binding site within the enzyme. Thermodynamic evidences highlight the significance of van der Waals interactions and hydrogen bonding in the binding process. The results of molecular docking indicated that both C1 and C2 effectively obstruct the entrance to hCA II's active site, with no significant differences in their binding conformations.
CONCLUSION: While C1 and C2 exhibit CA inhibitory potency lower than that of sulfonamide compounds, this study offers valuable insights that could pave the way for the development of a promising scaffold for designing new carbonic anhydrase inhibitors.
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.
OBJECTIVE: This systematic review and meta-analysis assess the effectiveness of salivary biomarkers in the diagnosis and prognosis of RA, examining current evidence and proposing avenues for future research.
METHODOLOGY: A literature review following PRISMA 2021 guidelines was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies from the past five years on salivary biomarkers in RA patients compared to healthy controls.
RESULT: The review focused on original research articles, and meta-analysis was performed on studies reporting standard deviation values for inflammatory markers such as IL-6, IL-8, MMP-8, and TNF-alpha. The meta-analysis included eleven studies with 394 RA patients and 255 healthy controls, evaluating IL-8, IL-6, MMP-8, and TNF-α as RA biomarkers. IL-8 showed a mean difference of 7.32 (CI: -5.48 to 20.13), not statistically significant, favouring controls. IL-6 had a CI of -0.09 (CI: -2.20 to 2.02) with high heterogeneity (I² = 98%), suggesting its potential as a diagnostic and prognostic biomarker. TNF-α and MMP-8 showed no significant differences (CIs: 4.54 and 2.71, respectively).
CONCLUSION: This systematic review and meta-analysis emphasize saliva's potential in identifying RA biomarkers, especially IL-6, which is associated with the disease's pathogenesis. However, significant evidence heterogeneity necessitates larger, multicentric studies for validation.
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.