OBJECTIVES: The objectives of this study were to identify the top differentially expressed miRNAs (DE-miRNAs) and their corresponding targets in hub gene-miRNA networks, as well as identify novel DE-miRNAs by analyzing three distinct microarray datasets. Additionally, functional enrichment analysis was performed using bioinformatics approaches. Finally, interactions between the 5 top-ranked hub genes and drugs were investigated.
METHODS: Using bioinformatics approaches, three GC profiles from the gene expression omnibus (GEO), namely gene expression omnibus series (GSE)-34526, GSE114419, and GSE137684, were analyzed. Targets of the top DE-miRNAs were predicted using the multiMiR R package, and only miRNAs with validated results were retrieved. Genes that were common between the "DE-miRNA prediction results" and the "existing tissue DE-mRNAs" were designated as differentially expressed genes (DEGs). Gene ontology (GO) and pathway enrichment analyses were implemented for DEGs. In order to identify hub genes and hub DE-miRNAs, the protein-protein interaction (PPI) network and miRNA-mRNA interaction network were constructed using Cytoscape software. The drug-gene interaction database (DGIdb) database was utilized to identify interactions between the top-ranked hub genes and drugs.
RESULTS: Out of the top 20 DE-miRNAs that were retrieved from the GSE114419 and GSE34526 microarray datasets, only 13 of them had "validated results" through the multiMiR prediction method. Among the 13 DE-miRNAs investigated, only 5, namely hsa-miR-8085, hsa-miR-548w, hsa-miR-612, hsa-miR-1470, and hsa-miR-644a, demonstrated interactions with the 10 hub genes in the hub gene-miRNA networks in our study. Except for hsa-miR-612, the other 4 DE-miRNAs, including hsa-miR-8085, hsa-miR-548w, hsa-miR-1470, and hsa-miR-644a, are novel and had not been reported in PCOS pathogenesis before. Also, GO and pathway enrichment analyses identified "pathogenic E. coli infection" in the Kyoto encyclopedia of genes and genomes (KEGG) and "regulation of Rac1 activity" in FunRich as the top pathways. The drug-hub gene interaction network identified ACTB, JUN, PTEN, KRAS, and MAPK1 as potential targets to treat PCOS with therapeutic drugs.
CONCLUSIONS: The findings from this study might assist researchers in uncovering new biomarkers and potential therapeutic drug targets in PCOS treatment.
OBJECTIVE: In this study, the antioxidative and anti-neuroinflammatory effects of SECA and its fractions were explored on lipopolysaccharides (LPS)-induced microglial cells.
METHODS: HPLC measured the four triterpenes in SECA and its fractions. SECA and its fractions were tested for cytotoxicity on microglial cells using MTT assay. NO, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and MDA (lipid peroxidation) produced by LPS-induced microglial cells were measured by colorimetric assays and ELISA. Nrf2 and HO-1 protein expressions were measured using western blotting.
RESULTS: The SECA and its fractions were non-toxic to BV2 microglial cells at tested concentrations. The levels of NO, TNF-α, IL-6, ROS, and lipid peroxidation in LPS-induced BV2 microglial cells were significantly reduced (p
OBJECTIVES: To assess the effectiveness of healthcare interventions strategies to systematically improve identification of familial hypercholesterolaemia in primary care and other community settings compared to usual care (incidental approaches to identify familial hypercholesterolaemia in primary care and other community settings).
SEARCH METHODS: We searched the Cochrane Inborn Errors of Metabolism Trials Register. Date of last search: 13 September 2021. We also searched databases (Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, PubMed, Embase, CINAHL, Web of Science, and SCOPUS) as well as handsearching relevant conference proceedings, reference lists of included articles, and the grey literature. Date of last searches: 05 March 2020. SELECTION CRITERIA: As per the Effective Practice and Organisation of Care (EPOC) Group guidelines, we planned to include randomised controlled trials (RCTs), cluster-RCTs and non-randomised studies of interventions (NRSI). Eligible NRSI were non-randomised controlled trials, prospective cohort studies, controlled before-and-after studies, and interrupted-time-series studies. We planned to selected studies with healthcare interventions strategies that aimed to systematically identify people with possible or definite clinical familial hypercholesterolaemia, in primary care and other community settings. These strategies would be compared with usual care or no intervention. We considered participants of any age from the general population who access primary care and other community settings.
DATA COLLECTION AND ANALYSIS: Two authors planned to independently select studies according to the inclusion criteria, to extract data and assess for risk of bias and the certainty of the evidence (according to the GRADE criteria). We contacted corresponding study authors in order to obtain further information for all the studies considered in the review.
MAIN RESULTS: No eligible RCTs or NRSIs were identified for inclusion, however, we excluded 28 studies.
AUTHORS' CONCLUSIONS: Currently, there are no RCTs or controlled NRSI evidence to determine the most appropriate healthcare strategy to systematically identify possible or definite clinical familial hypercholesterolaemia in primary care or other community settings. Uncontrolled before-and-after studies were identified, but were not eligible for inclusion. Further studies assessing healthcare strategies of systematic identification of familial hypercholesterolaemia need to be conducted with diagnosis confirmed by genetic testing or validated through clinical phenotype (or both).
MATERIALS AND METHODS: Epidemiological data for selfreported bone fractures were obtained through direct interviews using a validated questionnaire from the Prospective Urban and Rural Epidemiology (PURE) study.
RESULTS: Of 15,378 respondents, 6.63% (n=1019) reported bone fractures, with a higher proportion of men (65.8%, n=671) than women (34.2%, n=348). Higher odds of selfreporting bone fractures were seen in males (aOR, 2.12; 95%CI: 1.69, 2.65), those with a history of injury (aOR 5.01; 95%CI: 3.10, 6.32) and those who were obese (aOR: 1.46; 95% CI: 1.13, 1.89), highly active (aOR 1.25; 95%CI: 1.02, 1.53), smokers (aOR 1.35; 95%CI: 1.11, 1.65) and alcohol consumers (aOR 1.67; 95%CI: 1.20,2.32).
CONCLUSION: Adopting a healthier lifestyle that includes a balanced diet and moderate physical activity is critical for weight loss, increased muscle and bone mass and better stability, which reduces the likelihood of fractures following a fall.
OBJECTIVE: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting.
METHODS: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the "think-aloud" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool.
RESULTS: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023.
CONCLUSIONS: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47911.
METHODS: The study is completed in two phases. In phase I a cross-sectional study is performed using two quantitative research designs, i.e., exploratory and descriptive, to evaluate the knowledge of private pharmacy staff. The sample of 218 pharmacies was selected. While in phase II cross sectional survey is conducted in 10 facilities from where FDC anti TB drugs were sampled for analyzing their quality.
RESULT: Results revealed the presence of pharmacists only at 11.5% of pharmacies. Approximately 81% of staff at pharmacies had no awareness of MDR-TB, while 89% of pharmacies had no TB-related informative materials. The staff identified that most of the patients with TB (70%) were of poor socio-economic class, which restricted their purchase of four FDCs only up to 2-3 months. Only 23% were acquainted with the Pakistan National TB Program (NTP). Except for MDR-TB, the results showed a significant correlation between the experiences of staff with TB awareness. Findings from the quality evaluation of four FDC-TB drugs indicated that the dissolution and content assay of rifampicin were not according to the specifications, and overall, 30% of samples failed to comply with specifications. However, the other quality attributes were within the limits.
CONCLUSION: In light of the data, it can be concluded that private pharmacies could be crucial to the effective management of NTP through the timely identification of patients with TB, appropriate disease and therapy-related education and counseling, and proper storage and stock maintenance.
PATIENTS AND METHODS: A total of 70 children with myopia (aged 8-9 years old) were recruited. A total of 45 children were fitted with Ortho-K, and 25 were fitted with SVS. The PEL and axial length (AL) were measured by using MRI 3-Tesla, whereas central and peripheral refraction (PR) measurements were conducted at ±30 degrees horizontally with nasal (N) and temporal (T) intervals of 10°, 20°, and 30° and with an open field autorefractometer (WAM-5500 Grand Seiko). All the measurements were conducted at the baseline and 12 months.
RESULTS: The MRI analysis indicates that at 12 months, the SVS group showed more elongation of the PEL and AL at all eccentricities than the Ortho-K group did (p < 0.05). The Ortho-K group only showed significant PEL elongation beyond 20 degrees at N20, N30, T20, and T30 (p < 0.05); however, a significant reduction in the AL was detected in the center AL, N10, and T10 (p < 0.05). All eccentricities in the relative PR of the Ortho-K group were significantly more myopic than at the baseline (p < 0.05), whereas in the SVS group, all eccentricities in the relative PR were shown to be significantly more hyperopic than at the baseline (p < 0.05). The PEL and PR showed negative correlations at 12 months in the Ortho-K group.
CONCLUSION: MRI analysis can be utilized to describe changes in PEL in myopic children. It appears that as myopia progressed in Ortho-K lens wearers, the PEL increased by a greater amount than the AL did; thus, the retina was reshaped to become increasingly oblate and to display peripheral myopic defocus.
METHODS: Healthy school children aged < 10 years were invited to take part in this cross-sectional study. Refraction and best-corrected distance visual acuity (BCDVA) were determined using cycloplegic refraction and a logarithm of the minimum angle of resolution (logMAR) chart, respectively. All children underwent MRI using a 3-Tesla whole-body scanner. Quantitative eyeball measurements included the longitudinal axial length (LAL), horizontal width (HW), and vertical height (VH) along the cardinal axes. Correlation analysis was used to determine the association between the level of refractive error and the eyeball dimensions.
RESULTS: A total of 70 eyes from 70 children (35 male, 35 female) with a mean (standard deviation [SD]) age of 8.38 (0.49) years were included and analyzed. Mean (SD) refraction (spherical equivalent, SEQ) and BCDVA were -2.55 (1.45) D and -0.01 (0.06) logMAR, respectively. Ocular dimensions were greater in myopes than in emmetropes (all P < 0.05), with no significant differences according to sex. Mean (SD) ocular dimensions were LAL 24.07 (0.91) mm, HW 23.41 (0.82) mm, and VH 23.70 (0.88) mm for myopes, and LAL 22.69 (0.55) mm, HW 22.65 (0.63) mm, and VH 22.94 (0.69) mm for emmetropes. Significant correlations were noted between SEQ and ocular dimensions, with a greater change in LAL (0.46 mm/D, P < 0.001) than in VH (0.27 mm/D, P < 0.001) and HW (0.22 mm/D, P = 0.001).
CONCLUSIONS: Myopic eyeballs are larger than those with emmetropia. The eyeball elongates as myopia increases, with the greatest change in LAL, the least in HW, and an intermediate change in VH. These changes manifest in both sexes at a young age and low level of myopia. These data may serve as a reference for monitoring the development of refractive error in young Malaysian children of Chinese origin.