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

Food insecurity among immigrants and refugees of diverse origins living in metropolitan Atlanta: the roles of acculturation and social connectedness.

Little is known about the prevalence and correlates of food insecurity among immigrants and refugees. Acculturation and social connectedness may influence food insecurity (lack of access at all times to enough food for an active, healthy life) by affecting a person’s ability to access and use governmental and charitable food assistance programs, as well as other community-based or informal food-related resources. We explored associations of acculturation and social connectedness with food insecurity among diverse immigrants and refugees living in metropolitan Atlanta, a major destination for these populations in recent years. From 2017 to 2018, we surveyed 162 adults attending health fairs or programs hosted by two community-based organizations serving immigrants and refugees. Food insecurity within the past year was assessed using the American Academy of Pediatrics’ two-item questionnaire. Acculturation indicators included heritage culture and American acculturation scores (Vancouver Acculturation Index), English fluency, heritage language fluency, and percentage of lifetime in the USA. Social connectedness was operationalized using measures of religious attendance and social isolation. We conducted a multivariable logistic regression controlling for age, sex, education, household income, employment status, and household size. In the sample, 51.9% identified as Vietnamese, 16.0% Hispanic, 15.4% Burmese, 14.8% Bhutanese or Nepali, and 1.8% other. The average age was 39.10 (standard deviation [SD] =13.83), 34.0% were male, 73.8% had below a Bachelor’s degree, and 49.7% were unemployed. Average scores for American acculturation (mean [M] = 3.26, SD = 1.05, range 1–5) were lower than heritage acculturation (M = 4.34, SD = 0.68, range 1–5). Additionally, 43.4% were fluent in English. Average percentage of life in the USA was 40.59% (SD = 33.48). Regarding social connectedness, 55.9% regularly attended religious services. Average social isolation scores were 3.93 (SD = 1.34, range 3–9). Overall, past-year food insecurity was reported by 17.3% (34.6% in Hispanics, 24.0% in Burmese, 13.1% in Vietnamese, and 8.3% in Bhutanese or Nepali). In adjusted models, food insecurity was associated with English fluency (adjusted odds ratio [aOR] = 0.36, p = .03) and social isolation (aOR = 2.29, p < .001) but not other measures of acculturation or religious attendance. Limited English proficiency may make it more difficult to navigate or use governmental and charitable food assistance programs. Social isolation may hinder individuals from obtaining information about food assistance programs, receiving aid for services navigation, and sharing or borrowing food from family, friends, and neighbors. Interventions should seek to improve access to English language and literacy services, enhance the linguistic and cultural competency of service providers, and build social connectedness among immigrants and refugees

Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors : a multicenter IMWG study

Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T0 was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T0 was 3.1 years. The median number of lines of therapy before T0 was 4 (range 3-13). The median overall survival (OS) from T0 for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T0 in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T0 of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated.Leukemia advance online publication, 16 June 2017; doi:10.1038/leu.2017.138

High-affinity binding of Chp1 chromodomain to K9 methylated histone H3 is required to establish centromeric heterochromatin

In fission yeast, assembly of centromeric heterochromatin requires the RITS complex, which consists of Ago1, Tas3, Chp1, and siRNAs derived from centromeric repeats. Recruitment of RITS to centromeres has been proposed to depend on siRNA-dependent targeting of Ago1 to centromeric sequences. Previously, we demonstrated that methylated lysine 9 of histone H3 (H3K9me) acts upstream of siRNAs during heterochromatin establishment. Our crystal structure of Chp1's chromodomain in complex with a trimethylated lysine 9 H3 peptide reveals extensive sites of contact that contribute to Chp1's high-affinity binding. We found that this high-affinity binding is critical for the efficient establishment of centromeric heterochromatin, but preassembled heterochromatin can be maintained when Chp1's affinity for H3K9me is greatly reduced

New insights into the adsorption of Aurocyanide Ion on activated carbon surface: electron microscopy analysis and computational studies using fullerene-like models

Despite decades of concerted experimental studies dedicated to providing fundamental insights into the adsorption of aurocyanide ion, Au(CN) 2 -, on activated carbon (AC) surface, such a mechanism is still poorly understood and remains a contentious issue. This adsorption process is an essential unit operation for extracting gold from ores using carbon-in-pulp (CIP) technology. We hereby attempt to shed more light on the subject by employing a range of transmission electron microscopy (TEM) associated techniques. Gold-based clusters on the AC surface are observed by Z-contrast scanning TEM imaging and energy-filtered TEM element mapping and are supported by X-ray microanalysis. Density functional theory (DFT) calculations are applied to investigate this adsorption process for the first time. Fullerene-like models incorporating convex, concave, or planar structure which mimic the eclectic porous structures on the AC surface are adopted. Pentagonal, hexagonal, and heptagonal arrangements of carbon rings are duly considered in the DFT study. By determining the favored adsorption sites in water environment, a general adsorption trend of Au(CN)2 - adsorbed on AC surface is revealed whereby concave > convex ≈ planar. The results suggest a tendency for Au(CN)2 - ion to adsorb on the carbon sheet defects or edges rather than on the basal plane. In addition, we show that the adsorption energy of Au(CN)2 - is approximately 5 times higher than that of OH- in the alkaline environment (in negative ion form), compared to only about 2 times in acidic environment (in protonated form), indicating the Au extraction process is much favored in basic condition. The overall simulation results resolve certain ambiguities about the adsorption process for earlier studies. Our findings afford crucial information which could assist in enhancing our fundamental understanding of the CIP adsorption process