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

Disorders of sex development : insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46, XY DSD and 48 with 46, XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46, XY DSD. In patients with 46, XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes

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

Synchronous online English language teaching for young learners: insights from public primary school teachers in an EFL context

This study explored teachers’ perceived benefits, issues and their responses to the issues when conducting synchronous online English language teaching (SOELT) for young learners via the lens of the capital framework. A mixed-methods design using in-depth interviews and a Likert-scale survey was adopted to investigate the perceptions of 124 Vietnamese EFL teachers in different public primary schools in Vietnam. Quantitative analyses revealed teachers’ little access to economic capital as compared to social and cultural capital when conducing SOELT. Content-based analyses of interview data show that conducting SOELT for young learners increased teachers’ access to social and cultural capital in the form of 1) enhanced online pedagogical skills, 2) greater awareness of the potential of technologies for online teaching and professional development, and 3) increased collaboration among colleagues and students’ parents. However, the lack of economic capital created issues for implementing SOELT. Notably, teachers’ perceptions appeared to be contradictory because they reported good access to social and cultural capital, but they stated multiple issues related to the access to these two types of capital. The interviews also revealed teachers’ adoption of two strategies to resolve emergent SOELT issues: approach coping and avoidant coping strategies. Besides, the results show that teachers’ degrees of access to capital were not associated with their background characteristics. The results overall indicate benefits and issues of SOELT that are both common to online education and specific to the characteristics of young learners

Spatial Analysis For Simulation The Changing Of Inland Water Depth: A Case Study In The Mekong Delta, Vietnam

Vietnam is one of the most affected countries by the global sea-level rise, in which the Mekong Delta is the most heavily impacted area due to the low-lying position. By combining spatial geostatistics and Kriging interpolation techniques to delineate the elevation maps with the assumption of inland water level increasing under sea-level rise by interpolating 967 elevations geo-rectified data from the topographic map at 1/250,000 scale. The inland water level maps with different inundated inland water level scenarios from 0.2 to 2.8m were delineated.The result showed that the exponential model selected for interpolation of elevation data, distance A0 = 585.900 meters; coefficiency R2 = 0,985; and Residue Sum of Square RSS = 0,0011; which were suitable and thus was used for interpolation. Inland inundated water levels maps of 14 sea level rise scenarios from 0.2 to 2.8m were delineated. They also evaluated the Impact on inland water level rise, based on the pressure of sea-level rise on land lost, population migration, and food security of the Mekong River Delta. As a result, the Mekong Delta has initially affected water levels rise at 0.6m, and the whole region will be affected due to sea-level rise up to 2.8m. In these scenarios, part of the Ca Mau peninsula such as Bac Lieu, Ca Mau, and Kien Giang provinces will be most affected

Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins

Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins

Simulated Microgravity Induces the Proliferative Inhibition and Morphological Changes in Porcine Granulosa Cells

Astronauts are always faced with serious health problems during prolonged spaceflights. Previous studies have shown that weightlessness significantly affects the physiological function of female astronauts, including a change in reproductive hormones and ovarian cells, such as granulosa and theca cells. However, the effects of microgravity on these cells have not been well characterized, especially in granulosa cells. This study aimed to investigate the effects of simulated microgravity (SMG) on the proliferation and morphology of porcine granulosa cells (pGCs). pGC proliferation from the SMG group was inhibited, demonstrated by the reduced O.D. value and cell density in the WST-1 assay and cell number counting. SMG-induced pGCs exhibited an increased ratio of cells in the G0/G1 phase and a decreased ratio of cells in the S and G2/M phase. Western blot analysis indicated a down-regulation of cyclin D1, cyclin-dependent kinase 4 (cdk4), and cyclin-dependent kinase 6 (cdk6), leading to the prevention of the G1-S transition and inducing the arrest phase. pGCs under the SMG condition showed an increase in nuclear area. This caused a reduction in nuclear shape value in pGCs under the SMG condition. SMG-induced pGCs exhibited different morphologies, including fibroblast-like shape, rhomboid shape, and pebble-like shape. These results revealed that SMG inhibited proliferation and induced morphological changes in pGCs

Effect of the Optimize Heart Failure Care Program on clinical and patient outcomes – The pilot implementation in Vietnam

Background: The Ho-Chi-Minh-city Heart Institute in Vietnam took part in the Optimize Heart Failure (OHF) Care Program, designed to improve outcomes following heart failure (HF) hospitalization by increasing patient awareness and optimizing HF treatment. Methods: HF patients hospitalized with left ventricular ejection-fraction (LVEF) <50% were included. Patients received guideline-recommended HF treatment and education. Clinical signs, treatments and outcomes were assessed at admission, discharge, 2 and 6 months (M2, M6). Patients' knowledge and practice were assessed at M6 by telephone survey. Results: 257 patients were included. Between admission and M2 and M6, heart rate decreased significantly, and clinical symptoms improved significantly. LVEF increased significantly from admission to M6. 85% to 99% of patients received education. At M6, 45% to 78% of patients acquired knowledge and adhered to practice regarding diet, exercise, weight control, and detection of worsening symptoms. High use of renin-angiotensin-aldosterone-system inhibitors (91%), mineralocorticoid-receptor-antagonists (77%) and diuretics (85%) was noted at discharge. Beta-blocker and ivabradine use was less frequent at discharge but increased significantly at M6 (from 33% to 51% and from 9% to 20%, respectively, p < 0.001). There were no in-hospital deaths. Readmission rates at 30 and 60 days after discharge were 8.3% and 12.5%, respectively. Mortality rates at 30 days, 60 days and 6 months were 1.2%, 2.5% and 6.4%, respectively. Conclusions: The OHF Care Program could be implemented in Vietnam without difficulty and was associated with high usage of guideline-recommended drug therapy. Although education was delivered, patient knowledge and practice could be further improved at M6 after discharge. Keywords: Heart failure, Optimize, Education, Knowledge, Mortality, Readmissio