MATERIALS AND METHODS: Fifty adult Male Sprague Dawley rats were divided into five groups: control, LPS (5 mg/kg), LPS treated with minocycline (25 mg/kg), LPS treated with minocycline (50 mg/kg) and LPS treated with memantine (10 mg/kg). The immunohistochemistry and western blotting were used to analyse the expressions and densities of microglia marker (Iba-1) and astrocyte marker, (GFAP) while enzyme-linked immunosorbent assay (ELISA) was used to measure the protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels.
RESULTS: In comparison to the control group, the expression and density of Iba-1 and GFAP were significantly enhanced in the LPS group (p
METHODS: Data from the Global Burden of Disease Study (GBD) 2019 were analyzed, adopting Sawyer's broad definition of adolescence encompassing ages 10 to 24. Estimated annual percentage changes (EAPCs) were used to assess temporal trends.
RESULTS: Globally, from 1990 to 2019, there was a decrease in the ASIR of depression in adolescents (EAPC = -0.23). Notably, this decrease was more pronounced in female adolescents compared to their male counterparts (EAPC = -0.12 and - 0.29, respectively). Conversely, high Sociodemographic Index (SDI) regions experienced a significant increase in the ASIR of depression among adolescents (EAPC = 0.87). Furthermore, it is worth mentioning that individuals aged 20-24 exhibited the highest incidence rate for depression followed by those aged 15-19 and then those aged 10-14. The largest increases in the ASIRs of depression occurred in High-income North America (EAPC = 1.19) and Malaysia (EAPC = 2.4), respectively.
LIMITATIONS: Mathematical models were used to reconstruct and adjust data of different qualities, which might have introduced bias.
CONCLUSIONS: The global burden of disease for depression among adolescents aged 10-24 years declined from 1990 to 2019. Special attention must be paid to older adolescents and areas with higher SDIs.
METHODS: Using data from the International Sex Survey (N = 82,243; Mage = 32.39; SDage = 12.52; women: n = 46,874; 57 %), we examined the reliability of depression and anxiety symptom scores of the BSI-18, as well as evaluated evidence of construct, invariance, and criterion-related validity in predicting clinically relevant variables across countries, languages, genders, and sexual orientations.
RESULTS: Results corroborated an invariant, two-factor structure across all groups tested, exhibiting excellent reliability estimates for both subscales. The 'caseness' criterion effectively discriminated among those at low and high risk of depression and anxiety, yielding differential effects on the clinical criteria examined.
LIMITATIONS: The predictive validation was not made against a clinical diagnosis, and the full BSI-18 scale was not examined (excluding the somatization sub-dimension), limiting the validation scope of the BSI-18. Finally, the study was conducted online, mainly by advertisements through social media, ultimately skewing our sample towards women, younger, and highly educated populations.
CONCLUSIONS: The results support that the BSI-12 is a valid and reliable assessment tool for assessing depression and anxiety symptoms across countries, languages, genders, and sexual orientations. Further, its caseness criterion can discriminate well between participants at high and low risk of depression and anxiety.
DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter.
PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries.
INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration.
MAIN OUTCOME MEASURES: Enucleation and death.
RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively.
CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
METHODS AND RESULTS: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction.
CONCLUSIONS: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes.
MATERIALS AND METHODS: In silico Molecular Dynamics (MD) was used to determine the interactions of K21 inside the pocket of the targeted protein (crystal structure of fibroblast collagenase-1 complexed to a diphenyl-ether sulphone based hydroxamic acid; PDB ID: 966C; Crystal structure of MMP-2 active site mutant in complex with APP-derived decapeptide inhibitor. MD simulations were accomplished with the Desmond package in Schrödinger Drug Discovery Suite. Blood samples (~ 0.5 mL) collected into K2EDTA were immediately transferred for further processing using the Litron MicroFlow® PLUS micronucleus analysis kit for mouse blood according to the manufacturer's instructions. Bacterial Reverse Mutation Test of K21 Molecule was performed to evaluate K21 and any possible metabolites for their potential to induce point mutations in amino acid-requiring strains of Escherichia coli (E. coli) (WP2 uvrA (tryptophan-deficient)).
RESULTS: Molecular Simulation depicted that K21 has a specific pocket binding on various MMPs and SrtA surfaces producing a classical clouting effect. K21 did not induce micronuclei, which are the result of chromosomal damage or damage to the mitotic apparatus, in the peripheral blood reticulocytes of male and female CD-1 mice when administered by oral gavage up to the maximum recommended dose of 2000 mg/kg. The test item, K21, was not mutagenic to Salmonella typhimurium (S. typhimurium) strains TA98, TA100, TA1535 and TA1537 and E. coli strain WP2 uvrA in the absence and presence of metabolic activation when tested up to the limit of cytotoxicity or solubility under the conditions of the test.
CONCLUSION: K21 could serve as a potent protease inhibitor maintaining the physical and biochemical properties of dental structures.
OBJECTIVES: To evaluate the benefits and harms of any type of endoscopic sphincterotomy compared with a placebo drug, sham operation, or any pharmaceutical treatment, administered orally or endoscopically, alone or in combination, or a different type of endoscopic sphincterotomy in adults with biliary sphincter of Oddi dysfunction.
SEARCH METHODS: We used extensive Cochrane search methods. The latest search date was 16 May 2023.
SELECTION CRITERIA: We included randomised clinical trials assessing any type of endoscopic sphincterotomy versus placebo drug, sham operation, or any pharmaceutical treatment, alone or in combination, or a different type of endoscopic sphincterotomy in adults diagnosed with sphincter of Oddi dysfunction, irrespective of year, language of publication, format, or outcomes reported.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and Review Manager to prepare the review. Our primary outcomes were: proportion of participants without successful treatment; proportion of participants with one or more serious adverse events; and health-related quality of life. Our secondary outcomes were: all-cause mortality; proportion of participants with one or more non-serious adverse events; length of hospital stay; and proportion of participants without improvement in liver function tests. We used the outcome data at the longest follow-up and the random-effects model for our primary analyses. We assessed the risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We planned to present the results of time-to-event outcomes as hazard ratios (HR). We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI).
MAIN RESULTS: We included four randomised clinical trials, including 433 participants. Trials were published between 1989 and 2015. The trial participants had sphincter of Oddi dysfunction. Two trials were conducted in the USA, one in Australia, and one in Japan. One was a multicentre trial conducted in seven US centres, and the remaining three were single-centre trials. One trial used a two-stage randomisation, resulting in two comparisons. The number of participants in the four trials ranged from 47 to 214 (median 86), with a median age of 45 years, and the mean proportion of males was 49%. The follow-up duration ranged from one year to four years after the end of treatment. All trials assessed one or more outcomes of interest to our review. The trials provided data for the comparisons and outcomes below, in conformity with our review protocol. The certainty of evidence for all the outcomes was very low. Endoscopic sphincterotomy versus sham Endoscopic sphincterotomy versus sham may have little to no effect on treatment success (RR 1.05, 95% CI 0.66 to 1.66; 3 trials, 340 participants; follow-up range 1 to 4 years); serious adverse events (RR 0.71, 95% CI 0.34 to 1.46; 1 trial, 214 participants; follow-up 1 year), health-related quality of life (Physical scale) (MD -1.00, 95% CI -3.84 to 1.84; 1 trial, 214 participants; follow-up 1 year), health-related quality of life (Mental scale) (MD -1.00, 95% CI -4.16 to 2.16; 1 trial, 214 participants; follow-up 1 year), and no improvement in liver function test (RR 0.89, 95% CI 0.35 to 2.26; 1 trial, 47 participants; follow-up 1 year), but the evidence is very uncertain. Endoscopic sphincterotomy versus endoscopic papillary balloon dilation Endoscopic sphincterotomy versus endoscopic papillary balloon dilationmay have little to no effect on serious adverse events (RR 0.34, 95% CI 0.04 to 3.15; 1 trial, 91 participants; follow-up 1 year), but the evidence is very uncertain. Endoscopic sphincterotomy versus dual endoscopic sphincterotomy Endoscopic sphincterotomy versus dual endoscopic sphincterotomy may have little to no effect on treatment success (RR 0.65, 95% CI 0.32 to 1.31; 1 trial, 99 participants; follow-up 1 year), but the evidence is very uncertain. Funding One trial did not provide any information on sponsorship; one trial was funded by a foundation (the National Institutes of Diabetes and Digestive and Kidney Diseases, NIDDK), and two trials seemed to be funded by the local health institutes or universities where the investigators worked. We did not identify any ongoing randomised clinical trials.
AUTHORS' CONCLUSIONS: Based on very low-certainty evidence from the trials included in this review, we do not know if endoscopic sphincterotomy versus sham or versus dual endoscopic sphincterotomy increases, reduces, or makes no difference to the number of people with treatment success; if endoscopic sphincterotomy versus sham or versus endoscopic papillary balloon dilation increases, reduces, or makes no difference to serious adverse events; or if endoscopic sphincterotomy versus sham improves, worsens, or makes no difference to health-related quality of life and liver function tests in adults with biliary sphincter of Oddi dysfunction. Evidence on the effect of endoscopic sphincterotomy compared with sham, endoscopic papillary balloon dilation,or dual endoscopic sphincterotomyon all-cause mortality, non-serious adverse events, and length of hospital stay is lacking. We found no trials comparing endoscopic sphincterotomy versus a placebo drug or versus any other pharmaceutical treatment, alone or in combination. All four trials were underpowered and lacked trial data on clinically important outcomes. We lack randomised clinical trials assessing clinically and patient-relevant outcomes to demonstrate the effects of endoscopic sphincterotomy in adults with biliary sphincter of Oddi dysfunction.
METHODS: We conducted in-depth virtual interviews with pregnant women between February and April 2022. The interviews were recorded and transcribed, and data were analyzed by content analysis.
RESULTS: The majority of the participants demonstrated a commendable level of awareness regarding the signs and symptoms associated with ZIKV infection. They also exhibited a clear understanding of preventive measures, particularly emphasizing the importance of avoiding mosquito bites to minimize the risk of ZIKV transmission. However, a noteworthy gap in knowledge surfaced as a subset of participants remained uninformed about the potential for sexual transmission of ZIKV, which could lead to congenital ZIKV in pregnant women. Even among women who were cognizant of ZIKV and its potential negative health outcomes, associated with the infection, many of them did not perceive themselves to be at risk, mainly because ZIKV infection is infrequently discussed or heard of, leading to a sense of infections' rarity. While the adoption of preventive measures such as mosquito bite prevention during pregnancy was a common practice, however, prevention of sexually transmitted infections (STIs) including mosquito-borne diseases such as Zika is low. A minority of women express concerns about the sensitivity surrounding discussions and prevention of STIs within the context of marriage. Most of the participants were supportive of the provision of awareness of ZIKV infection in women during pregnancy and the involvement of men, especially in initiatives aimed at preventing transmission through sexual contact.
CONCLUSION: This study uncovered gaps in both knowledge and practices pertaining ZIKV infection among pregnant women in the aftermath of the ZIKV pandemic. The insights gleaned from our research are valuable for shaping future interventions geared towards preventing the resurgence or facilitating the sustainable eradication of ZIKV.
PURPOSE: We aimed to examine the role of age-dependent intervention thresholds (ITs) applied to the Fracture Risk Assessment (FRAX) tool in therapeutic decision making for osteoporosis in the Malaysian population.
METHODS: Data were collated from 1380 treatment-naïve postmenopausal women aged 40-85 years who underwent bone mineral density (BMD) measurements for clinical reasons. Age-dependent ITs, for both major osteoporotic fracture (MOF) and hip fracture (HF), were calculated considering a woman with a BMI of 25 kg/m2, aged between 40 and 85years, with a prior fragility fracture, sans other clinical risk factors. Those with fracture probabilities equal to or above upper assessment thresholds (UATs) were considered to have high fracture risk. Those below the lower assessment thresholds (LATs) were considered to have low fracture risk.
RESULTS: The ITs of MOF and HF ranged from 0.7 to 18% and 0.2 to 8%, between 40 and 85years. The LATs of MOF ranged from 0.3 to 11%, while those of HF ranged from 0.1 to 5.2%. The UATs of MOF and HF were 0.8 to 21.6% and 0.2 to 9.6%, respectively. In this study, 24.8% women were in the high-risk category while 30.4% were in the low-risk category. Of the 44.8% (n=618) in the intermediate risk group, after recalculation of fracture risk with BMD input, 38.3% (237/618) were above the ITs while the rest (n=381, 61.7%) were below the ITs. Judged by the Youden Index, 11.5% MOF probability which was associated with a sensitivity of 0.62 and specificity of 0.83 and 4.0% HF probability associated with a sensitivity of 0.63 and a specificity 0.82 were found to be the most appropriate fixed ITs in this analysis.
CONCLUSION: Less than half of the study population (44.8%) required BMD for osteoporosis management when age-specific assessment thresholds were applied. Therefore, in more than half, therapeutic decisions can be made without BMD based on these assessment thresholds.
METHODS AND ANALYSIS: REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18-80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app.
ETHICS AND DISSEMINATION: The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.
METHODS: We obtained information on medication use and cancer diagnosis from National Health and Nutrition Examination Survey participants. After propensity score matching, we conducted survey-weighted multivariate logistic regression and restricted cubic spline analysis to assess the observed correlation between medication use and cancer while adjusting for multiple covariates. We also performed MR analysis to investigate causality based on summary data from genome-wide association studies on medication use and cancers. We performed sensitivity analyses, replication analysis, genetic correlation analysis, and reverse MR analysis to improve the reliability of MR findings.
RESULTS: We found that the use of agents acting on the renin-angiotensin system was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.42; 95% confidence interval (CI) = 0.27-0.63, P