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

Potential of Phosphorus Solubilizing Purple Nonsulfur Bacteria Isolated from Acid Sulfate Soil in Improving Soil Property, Nutrient Uptake, and Yield of Pineapple (Ananas comosus L. Merrill) under Acidic Stress

This study aimed to (i) evaluate purple nonsulfur bacteria (PNSB) strains possessing the highest phosphorus (P) solubilizing capacity in field and (ii) determine the efficacy of PNSB biofertilizers in improving soil quality, P uptake, growth, and yield of pineapple cultivated in acid sulfate soil (ASS). A field experiment was conducted in a completely randomized block design with two factors, including the first factor as P fertilizer levels (0, 50, 75, and 100% P) based on recommended fertilizer formula (RFF) and the second factor as supplementation of biofertilizers containing P solubilizing PNSB (no inoculated PNSB, Rhodobacter sphaeroides W48, R. sphaeroides W42, and a mixture of R. sphaeroides W48 and W42). The results indicated that the supplementation of PNSB biofertilizers led to an increase of 25.3–33.9% in soluble P concentration in soil compared to control treatment. Among the selected PNSB strains, R. sphaeroides W42 and a mixture of the PNSB in biofertilizers solubilized all insoluble P fractions (Fe-P, Al-P, and Ca-P) and strain W48 in biofertilizers for Fe-P and Al-P. Furthermore, the supplementation of biofertilizers from R. sphaeroides W48 and W42 individually and their mixture raised plant height by 3.56–4.10% and available P concentration by 25.3–33.9%. Total P uptake in pineapple treatments with biofertilizers from mixed PNSB was 42.9% higher than that in the control treatment (p<0.05). Application of mixed PNSB strains can reduce 25% P of chemical fertilizer, but the pineapple yield rose over 12.1%. Both R. sphaeroides W48 and W42 are potent for use as crop yield enhancers to obtain the sustainable pineapple cultivation under acidic stress

Developing a nutritious soup product using purple sweet potatoes supplemented with composite of vegetables and freezed-dried chicken

Abstract This research aimed to develop a nutritious instant purple sweet potato soup (PSP) combination with a variety of vegetables and freeze-dried chicken. The nutritional characteristics of the product were evaluated. The current study employs principal component analysis (PCA), consumer preference mapping, and check-all-that-apply (CATA) data processing to describe sensory instant mixed soup attributes. The results showed that the soup was made from the formula F2 (PSP flour 47.5%, orange-fleshed sweet potato flour 12.5%, potatoes 6%, banana 7%, mushroom 8%, petit poise 3%, pumpkin 5%, protein powder 5% and cream powder 6%) gave good quality, high sensory value and attractive colors product. The PCA identified important soup attributes such as sweetness, milk flavor, vegetable odor, and color. Adding 15% freeze-dried chicken improved the quality of mixed soup products with energy distribution from macronutrients: proteins 24%, carbohydrates 65%, and lipids 10%. The anthocyanin and β-carotene content analyzed from the product was 13.1 mg/100 g and 370.2 μg/100 g. Score analysis according to the CATA model with two main components accounting for 95.57% of the variance in sensory attribute data, showing liking attributes of mixed soup sample that the panelists preferred in color, flavor, chicken meat distribution, and sweetness. The essential nutritional characteristics of mixed soup have been carefully analyzed

Optimization of Mulberry Extract Foam-Mat Drying Process Parameters

Mulberry powder was created from the extract using a foam-mat drying process. The studies aimed to evaluate the effects of egg albumin, carboxymethyl cellulose (CMC), digestion-resistant maltodextrin (DRM) contents, and whipping time (5 to 15 min) on the foam properties. The impact of different drying temperatures (60 to 75 &deg;C) on the quality of the finished mulberry powder was also noted. The best foam expansion/stability value was determined using multiple regression models as a function of egg albumin, CMC, DRM, and whipping time. The results indicated that the main influencing factors for the foam properties were whipping time followed by egg albumin, CMC, and DRM. Optimum values of foam expansion and stability were achieved at 467.9% and 97.02%, respectively. The foam had a porous structure and good stability for subsequent drying, with optimal contents of egg albumin, CMC, and DRM used at 7.6%, 0.4%, and 2%, respectively, along with a whipping time of 14.5 min. The established models had a high coefficient of determination (R2 &gt; 0.9) and a high correlation between the predicted and observed values. Therefore, the model could be adjusted to determine the characteristics of the foam suitable for subsequent drying. The optimal values were then also verified. Minimal fluctuations (1.78&ndash;2.98%) between the experimental data and the optimal value were found. The drying temperature also significantly affected the quality of the mulberry powder. The foam was dried at 65 &deg;C for 4 h to produce apowder with a beautiful light color (L* = 62.65), a characteristic purple-red color of mulberry (a* = 5.97). The moisture, water activity, and anthocyanin content of the finished mulberry powder were 4.57%, 0.3, and 5.4 mg/g, respectively

Dual Stimuli-Responsive Multifunctional Silicon Nanocarriers for Specifically Targeting Mitochondria in Human Cancer Cells

Specific targeting, selective stimuli-responsiveness, and controlled release of anticancer agents are requested for high therapeutic efficiency with a minimal adverse effect. Herein, we report the sophisticated synthesis and functionalization of fluorescent mesoporous silicon (FMPSi) nanoparticles decorated with graphene oxide (GO) nanosheets. GO-wrapped FMPSi (FMPSi@GO) was loaded with a cisplatin (Cis) anticancer agent, and Cis-loaded FMPSi@GO (FMPSi-Cis@GO) exhibited the dual stimuli (pH and NIR)-responsiveness of controlled drug release, i.e., the drug release rate was distinctly enhanced at acidic pH 5.5 than at neutral pH 7.0 and further enhanced under NIR irradiation at acidic pH condition. Notably, dequalinium-conjugated FMPSi-Cis@GO (FMPSi-Cis@GO@DQA) demonstrated an excellent specificity for mitochondrial targeting in cancer cells without noticeable toxicity to normal human cells. Our novel silicon nanocarriers demonstrated not only stimuli (pH and NIR)-responsive controlled drug release, but also selective accumulation in the mitochondria of cancer cells and destroying them

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that 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 seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921