Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

CDK4/6 INHIBITORS AS NOVEL THERAPY IN NASOPHARYNGEAL CARCINOMA

Ph.DDOCTOR OF PHILOSOPHY (CSI

Bad phosphorylation as a target of inhibition in oncology

Bcl-2 agonist of cell death (BAD) is a BH3-only member of the Bcl-2 family which possesses important regulatory function in apoptosis. BAD has also been shown to possess many non-apoptotic functions closely linked to cancer including regulation of glycolysis, autophagy, cell cycle progression and immune system development. Interestingly, BAD can be either pro-apoptotic or pro-survival depending on the phosphorylation state of three specific serine residues (human S75, S99 and S118). Expression of BAD and BAD phosphorylation patterns have been shown to influence tumor initiation and progression and play a predictive role in disease prognosis, drug response and chemosensitivity in various cancers. This review aims to summarize the current evidence on the functional role of BAD phosphorylation in human cancer and evaluate the potential utility of modulating BAD phosphorylation in cancer

Exploring Students’ Engagement of Using Mediating Tools in E-Learning

People are looking for flexible learning ways to meet educational needs in today's world context. There is an increasing need and expectation for universities to incorporate technologies into the design and delivery. It is of significant interest whether the increased use of electronic tools and the provision of online teaching resources positively impact students. The function and influence that a mediation tool can have should be evaluated more closely, rather than viewing them as just assistance. Student involvement is generally regarded as an important benchmark and indication of the quality of the student experience in higher education. Still, the idea is challenging to define and is interpreted in various ways throughout the literature. Hence, this study explores how students experience online learning using the mediating tool. Semi-structured interviews were applied to determine the types of student engagement. The interviews were recorded and transcribed by thematic analysis (Braun and Clarke, 2006). The results showed that the mediating tool positively supports social engagement, behavioral engagement, collaborative engagement, emotional engagement, and cognitive engagement. Implications shed light on teachers, designers, and students when using the mediating tool in online learning

Procarcinogens – Determination and Evaluation by Yeast-Based Biosensor Transformed with Plasmids Incorporating RAD54 Reporter Construct and Cytochrome P450 Genes

International audienceIn Vietnam, a great number of toxic substances, including carcinogens and procarcinogens, from industrial and agricultural activities, food production, and healthcare services are daily released into the environment. In the present study, we report the development of novel yeast-based biosensor systems to determine both genotoxic carcinogens and procarcinogens by cotransformation with two plasmids. One plasmid is carrying human CPR and CYP (CYP3A4, CYP2B6, or CYP2D6) genes, while the other contains the RAD54-GFP reporter construct. The three resulting coexpression systems bearing both CPR-CYP and RAD54-GFP expression cassettes were designated as CYP3A4/CYP2B6/CYP2D6 + RAD54 systems, respectively and used to detect and evaluate the genotoxic potential of carcinogens and procarcinogens by selective activation and induction of both CPR-CYP and RAD54-GFP expression cassettes in response to DNA damage. Procarcinogens were shown to be predominantly, moderately or not bioactivated by one of the CYP enzymes and thus selectively detected by the specific coexpression system. Aflatoxin B-1 and benzo(a) pyrene were predominantly detected by the CYP3A4 + RAD54 system, while N-nitrosodimethylamine only moderately activated the CYP2B6 + RAD54 reporter system and none of them was identified by the CYP2D6 + RAD54 system. In contrast, the genotoxic carcinogen, methyl methanesulfonate, was detected by all systems. Our yeast-reporter system can be performed in 384-well microplates to provide efficient genotoxicity testing to identify various carcinogenic compounds and reduce chemical consumption to about 53% as compared with existing 96-well genotoxicity bioassays. In association with a liquid handling robot, this platform enables rapid, cost-effective, and high-throughput screening of numerous analytes in a fully automated and continuous manner without the need for user interaction

Bacterial bloodstream infections in a tertiary infectious diseases hospital in Northern Vietnam: aetiology, drug resistance, and treatment outcome

Abstract Background Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. Methods A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if >48 h. Results A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36–60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. Conclusions Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam

Depressive Symptoms, Suicidal Ideation, and Mental Health Service Use of Industrial Workers: Evidence from Vietnam

Background: Depressive symptoms and suicidal ideation substantially reduce industrial workers&rsquo; productivity and performance. This study was performed to examine the prevalence of depressive symptoms and suicidal ideation and identify associated factors among industrial workers in different provinces of Vietnam. Materials and Methods: We performed a cross-sectional study in industrial zones of four provinces of Vietnam. The Patient Health Questionnaire (PHQ-9) was employed to screen depressive symptoms and suicidal ideation. Multivariate logistic regression was performed to determine factors related to depressive symptoms and suicidal ideation. Results: Of 1200 industrial workers, 30.5% and 33.6% industrial workers had positive depressive symptoms and suicidal ideation in the last two weeks, respectively. There were 38.3% ever using mental health services in the last 12 months. High school education (OR = 0.64, 95% CI = 0.44&ndash;0.95); living in dormitory (OR = 3.07, 95% CI = 1.51&ndash;6.24), living with siblings (OR = 2.98; 95% CI = 1.32&ndash;6.75), having two children or more (OR = 1.45, 95% CI = 1.03&ndash;2.03), high years of experience (OR = 0.94; 95% CI = 0.89&ndash;0.98), suffering from burnout, alcohol use disorder (OR = 2.38; 95% CI = 1.72&ndash;3.28), and smoking status (OR = 0.38, 95% CI = 0.23&ndash;0.61) were associated with positive depressive symptoms. Living with children, working in mechanical/metallurgy/electronics factories, completely exhausted and often thinking of quitting, and alcohol use disorder were positively related to suicidal ideation. Conclusions: This study found a high prevalence of depressive symptoms and suicidal ideation among industrial workers in Vietnam. Regular screening and detecting high-risk groups, along with interventions to reduce health risk behaviors, burnout and on-site medical service quality improvement, are recommended to alleviate the burden of depression in industrial workers

Summary and comparison of the results of the present study with the data from published report.

<p>Summary and comparison of the results of the present study with the data from published report.</p