OBJECTIVE : The sperm acrosome reaction is a Ca2+ -dependent exocytotic event that is triggered by adhesion to the mammalian egg's zona pellucida. Previous studies suggested a role of Ca2+ channels in acrosome reactions. This study was conducted to investigate the T-type calcium channel is operated in acrosome reaction of human spermatozoa. METHOD : Human semen samples were obtained from healthy donors with nomal criteria. The spermatozoa were divided into five groups: Group 1 were non-treated as a control; Group 2 where spermatozoa were exposed to 5 micrometer Ca2+ A23187 (Ca2+i); Group 3 where spermatozoa were exposed 5 micrometer Ca2+i and mibefradil; Group 4 where spermatozoa were exposed 5 micrometer Ca2+i and nifedipine, and Group 5 where spermatozoa were treated with 5 micrometer Ca2+i and both of mibefradil and nifedipine. Spermatozoa in all groups were retrieved after incubation for 15 and 30 minutes at 37degrees C. After staining with PSA-FITC, fluorescence was observed under a fluorescence microscope, and AR was evaluated on a total >100 spermatozoa/side. RESULT AND CONCLUSION : We observed on acrosome reaction inhibition rate in human spermatozoa the various of concentration of mibefradil, nifedipine. Maximum response was noted with 1.0 micrometer mibefradil and the decrease of acrosome reaction inhibition rate 45%. Nifedipine in acrosome reaction inhibition rate was only about 25%. The Ca2+i-induced AR of spermatozoa was significantly suppressed by mibefradil. Incidence of the suppression was depending on concentration of mibefradil. Results from the present study suggest that the human spermatozoa possess T-type channel. The observation that reversible inhibitor of T channels in male germ cells provides a new mechanism of contraceptive action.
Acrosome Reaction* ; Acrosome* ; Calcimycin ; Calcium Channels, T-Type ; Fluorescence ; Germ Cells ; Humans* ; Incidence* ; Male ; Mibefradil* ; Nifedipine ; Semen ; Spermatozoa* ; Tissue Donors ; Zona Pellucida

OBJECTIVE: Obesity has been shown to be associated with adverse outcomes in viral infections such as influenza, but previous studies on coronavirus disease 2019 (COVID-19) had mixed results. The aim of this systematic review is to investigate the relationship between COVID-19 and obesity. METHODS: We performed a systematic review and meta-analysis. A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL, OpenGrey and preprint servers medRxiv and bioRxiv was performed, with no restriction on language or date of publication. Primary outcomes of this study were intensive care unit (ICU) admission or critical disease, severe disease and mortality. Secondary outcome was a positive COVID-19 test. Meta-analysis was performed using OpenMeta-Analyst software, and heterogeneity was tested using Cochran's Q test and I2 statistic. The study protocol was registered on PROSPERO (CRD42020184953). RESULTS: A total of 1,493 articles were identified and 61 studies on 270,241 patients were included. The pooled prevalence of obesity was 27.6% (95% confidence interval [CI] 22.0-33.2) in hospitalised patients. Obesity was not significantly associated with increased ICU admission or critical illness (odds ratio [OR] 1.25, 95% CI 0.99-1.58, CONCLUSION Obesity increased the risk of severe disease, mortality and infection with COVID-19. Higher body mass index was associated with ICU admission and critical disease. Patients who are obese may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and infected patients should be monitored closely for adverse outcomes.
Body Mass Index ; COVID-19/therapy* ; Critical Care ; Critical Illness ; Global Health ; Hospitalization ; Humans ; Obesity/complications* ; Prognosis ; Risk Factors ; Severity of Illness Index

BACKGROUND:Intravenous fluid (IVF) is commonly used in acute clinical management. This study aimed to review the choice and primary considerations in IVF prescriptions and to evaluate the adequacy of guidelines and trainings on it in the New Territories West Cluster (NTWC) of Hong Kong. METHODS:This is a descriptive study based on data collected from an online survey. Data were processed by SPSS for statistical analysis. This study focused on a general description and doctor-nurse between group comparison. Participants were asked the choice of IVF for nine acute clinical scenarios and provide reason. A 1–10 scale was used to assess the sufficiency of guideline, training and information, and time for revision on IVF prescription. RESULTS:0.9％ sodium chloride was the most familiar IVF (36％), followed by 5％ Dextrose solution (26％). In the nine scenarios, the most chosen IVF was 0.9％ sodium chloride (37％–61％). There was significant difference in the choice of IVF between doctors and nurses in 7 cases. The second most chosen IVF for doctors was Plasma-Lyte A while that for nurses was Gelofusine. Departmental practice was the most chosen reason to account for the prescription. The adequacy of guideline, information and training, and time for revision was rated 5. Doctors had significantly more time at work than nurses to update knowledge in IVF prescription (5.41 versus 4.57). CONCLUSION:0.9％ sodium chloride was mostly chosen. The choice of IVF was mainly based on departmental practice. Adequacy of guideline, information and training, and time for revision on IVF prescription were average, indicating significant training deficit.

A risk management plan (RMP) contains an overview of important safety concerns associated with the use of a therapeutic product (TP) and proposed pharmacovigilance activities to monitor and manage these safety concerns in the post-approval stage. The Health Sciences Authority (HSA) of Singapore has legislated its requirements for RMPs as part of its product life cycle approach in the management of safety concerns associated with TPs. Under the Health Product (Therapeutic Products) Regulations enacted in November 2016, companies may be required to implement RMPs under the direction of HSA to help ensure that the benefits of TPs outweigh their risks. In this commentary, we present a case study on the local RMP for Dengvaxia®, the world's first dengue vaccine, which has been approved for use in Singapore. We hope that this article raises awareness among healthcare professionals about the concept of RMPs and how RMPs are implemented locally.

INTRODUCTIONDevice therapy is efficacious in preventing sudden cardiac death (SCD) in patients with reduced ejection fraction. However, few who need the device eventually opt to undergo implantation and even fewer reconsider their decisions after deliberation. This is due to many factors, including unresolved patient barriers. This study identified the factors that influenced patients' decision to decline implantable cardioverter defibrillator (ICD) implantation, and those that influenced patients who initially declined an implant to reconsider having one.

METHODSA single-centre survey was conducted among 240 patients who had heart failure with reduced ejection fraction and met the ICD implantation criteria, but had declined ICD implantation.

RESULTSParticipants who refused ICD implantation were mostly male (84%), Chinese (71%), married (72%), currently employed (54%), and had up to primary or secondary education (78%) and monthly income of < SGD 3,000 (51%). Those who were more likely to reconsider their decision were aware that SCD was a consequence of heart failure with reduced ejection fraction, knowledgeable of the preventive role of ICDs, currently employed and aware that their doctor strongly recommended the implant. Based on multivariate analysis, knowledge of the role of ICDs for primary prophylaxis was the most important factor influencing patient decision.

CONCLUSIONThis study identified the demographic and social factors of patients who refused ICD therapy. Knowledge of the role of ICDs in preventing SCD was found to be the strongest marker for reconsidering ICD implantation. Measures to address this information gap may lead to higher rates of ICD implantation.

Cross-Sectional Studies ; Death, Sudden, Cardiac ; prevention & control ; Defibrillators, Implantable ; Female ; Heart Failure ; mortality ; physiopathology ; therapy ; Humans ; Male ; Middle Aged ; Primary Prevention ; methods ; Risk Factors ; Singapore ; epidemiology ; Stroke Volume ; physiology ; Survival Rate ; trends

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.