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Background: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by amyloid-β (Aβ) plaques. Systemic inflammation and obesity may exacerbate AD pathogenesis. We previously reported anti-inflammatory and anti-obesity effects of EPA in mice., Objectives: We aimed to determine whether EPA reduces obesity-associated metabolic dysfunctions and Aβ accumulation in AD amyloidogenic mice., Methods: Two-mo-old APPswe/PS1dE9 transgenic (TG) mice and non-TG littermates were randomly assigned to low fat (LF; 10% kcal fat), high fat (HF; 45% kcal fat), or EPA (36 g/kg)-supplemented HF diets. Body composition, glucose tolerance, and energy expenditure were measured, and serum and brain metabolic markers were tested 38 wk postintervention. Outcomes were statistically analyzed via 3-factor ANOVA, modeling genotype, sex, and diet interactions., Results: HF-fed males gained more weight than females (Δ = 61 mg; P < 0.001). Compared with LF, HF increased body weights of wild-type (WT) males (Δ = 31 mg; P < 0.001). EPA reduced HF-induced weight gain in WT males (Δ = 24 mg; P = 0.054) but not in females. HF mice showed decreased glucose clearance and respiratory energy compared with LF-fed groups (Δ = -1.31 g/dL; P < 0.001), with no significant effects of EPA. However, EPA conferred metabolic improvements by decreasing serum leptin and insulin (Δ = -2.51 g/mL and Δ = -0.694 ng/mL, respectively compared with HF, P ≤ 0.05) and increasing adiponectin (Δ = 21.6 ng/mL; P < 0.001). As we expected, TG mice expressed higher serum and brain Aβ than WT mice (Δ = 0.131 ng/mL; P < 0.001 and Δ = 0.56%; P < 0.01, respectively), and EPA reduced serum Aβ 1-40 in TG males compared with HF (Δ = 0.053 ng/mL; P ≤ 0.05)., Conclusions: To our knowledge, this is the first report that EPA reduces serum Aβ 1-40 in obese AD male mice, warranting further investigations into tissue-specific mechanisms of EPA in AD., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airway disease. The epithelial-derived IL-33 and its receptor ST2 have been implicated in airway inflammation and infection. We aimed to determine whether astegolimab, a selective ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD., Methods: COPD-ST2OP was a single-centre, randomised, double-blinded, placebo-controlled phase 2a trial in moderate-to-very severe COPD. Participants were randomly assigned (1:1) with a web-based system to received 490 mg subcutaneous astegolimab or subcutaneous placebo, every 4 weeks for 44 weeks. The primary endpoint was exacerbation rate assessed for 48 weeks assessed with a negative binomial count model in the intention-to-treat population, with prespecified subgroup analysis by baseline blood eosinophil count. The model was the number of exacerbations over the 48-week treatment period, with treatment group as a covariate. Safety was assessed in the whole study population until week 60. Secondary endpoints included Saint George's Respiratory Questionnaire for COPD (SGRQ-C), FEV 1 , and blood and sputum cell counts. The trial was registered with ClinicalTrials.gov, NCT03615040., Findings: The exacerbation rate at 48 weeks in the intention-to-treat analysis was not significantly different between the astegolimab group (2·18 [95% CI 1·59 to 2·78]) and the placebo group (2·81 [2·05 to 3·58]; rate ratio 0·78 [95% CI 0·53 to 1·14]; p=0·19]). In the prespecified analysis stratifying patients by blood eosinophil count, patients with 170 or fewer cells per μL had 0·69 exacerbations (0·39 to 1·21), whereas those with more than 170 cells per μL had 0·83 exacerbations (0·49 to 1·40). For the secondary outcomes, the mean difference between the SGRQ-C in the astegolimab group versus placebo group was -3·3 (95% CI -6·4 to -0·2; p=0·039), and mean difference in FEV 1 between the two groups was 40 mL (-10 to 90; p=0·094). The difference in geometric mean ratios between the two groups for blood eosinophil counts was 0·59 (95% CI 0·51 to 0·69; p<0·001) and 0·25 (0·19 to 0·33; p<0·001) for sputum eosinophil counts. Incidence of treatment-emergent adverse events was similar between groups., Interpretation: In patients with moderate-to-very severe COPD, astegolimab did not significantly reduce exacerbation rate, but did improve health status compared with placebo., Funding: Funded by Genentech and National Institute for Health Research Biomedical Research Centres., Competing Interests: Declaration of interests CEB reports funding from Genentech to support this study; grants from AstraZeneca, GlaxoSmithKline, Roche/Genentech, Boehringer Ingelheim, Novartis, Chiesi, Merck Sharp & Dohme, Sanofi, Regeneron, 4DPharma, and Mologic; and consulting fee paid to institution from AstraZeneca, GlaxoSmithKline, Roche/Genentech, Boehringer Ingelheim, Novartis, Chiesi, Merck Sharp & Dohme, Sanofi, Regeneron, and 4DPharma. NJG reports an investigator led grant from GlaxoSmithKline; National Institute for Health Research fellowship; and lecture honoraria from GlaxoSmithKline and Chiesi. AW reports a research grant from Sanofi Genzyme. CJ reports a Medical Research Council clinical research training fellowship. MAG, DFC, and DC are employed by Genentech and receive stock options. All other authors declare no competing interests., (Crown Copyright © 2022 Published by Elsevier Ltd. All rights reserved.)

Background: Menopausal symptoms have negative effects on the aspects of quality of life and impose a high cost on the health system. In traditional Persian medicine, pomegranate is recommended to alleviate menopausal symptoms., Material and Methods: A randomized double-blind placebo-controlled trial was performed among 78 healthy women. Participants were interviewed three times: Before receiving the supplement/placebo, after completing the treatment, and after 3 weeks with no intervention. They filled out the demographic information sheet, modified-Kupperman index, and Menopause-Specific Quality of Life (MENQOL) questionnaires., Results: The mean scores of the modified-Kupperman index and MENQOL characteristics before and after the treatment and after the follow-up period were significantly different between pomegranate and placebo groups in both modified-Kupperman and MENQOL scores (p < 0.001)., Conclusion: This study demonstrated that 4 weeks' treatment with the pomegranate supplement significantly ameliorates the irritating symptoms of menopause and improves the quality of life in menopausal women even after 4 weeks' medicine deprivation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Fractional calculus is a powerful and effective tool for modeling of nonlinear systems. In this paper, we first introduce a modification of conformable fractional derivative to solve fractional infinite horizon optimal control problems. We point out that the term t 1-α in definition of conformable derivative has some disadvantages and thus must be refined. Using an interesting property of relationship between the presented fractional derivative and the usual first-order derivative, fractional dynamic system in the infinite horizon optimal control problem is transformed into a non-fractional one. By a suitable change of variable, the obtained infinite horizon problem is reduced to a finite-horizon one. According to the Pontryagin minimum principle for optimal control problems and by constructing an error function, an unconstrained minimization problem is then defined. In the achieved minimization problem, trial solutions for state, co-state and control functions are utilized where these trial solutions are constructed by using two-layered perceptron neural network. Some numerical results are solved to explain our main results. Two applicable examples as stabilization and chaos control of fractional order systems are also provided., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 ISA. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: The impact of combined omega-3 FAs and vitamin E supplementation on oxidative stress (OS) has been evaluated in several studies. However the results are inconsistent. Therefore, we performed a systematic review and meta-analysis to assess the role of omega-3 FAplus vitamin E on anti-oxidant and OS parameters., Methods: We searched five databases (PubMed, Embase, Web of Sciences, Scopus and the Cochrane Central Register of Controlled Trials) from inception until March 15th 2018 for RCT covering OS parameters combined with omega-3 FAs and vitamin E. The effect of omega-3 FAs plus vitamin E combination on OS factors was determined as the standardized mean difference (SMD) calculated according to DerSimonian and Laird for the random effects model., Results: Nine articles were included in our analyses, significant improvements were observed in trials supplementing with omega-3 FAs plus vitamin E vs placebo for total antioxidant capacity (TAC) (SMD=0.63, 95%CI: 0.31 to 0.95, P<0.001) and nitric oxide (NO) (SMD=0.55, 95%CI: 0.23 to 0.87, P<0.001). Significant reduction was observed for malondialdehyde (MDA) (SMD: -0.48, 95%CI: -0.68 to -0.28, P<0.001). However, the results of meta-analysis did not show a significant difference in levels of glutathione (GSH) (SMD=0.34, 95%CI: -0.07 to 0.75, P=0.10), superoxide dismutase (SOD) activity (SMD: 0.07, 95% CI: -0.58 to 0.73, P=0.82) and Catalase (CAT) activity (SMD: 0.74, 95% CI: -0.30 to 1.79, P=0.16)., Conclusion: Co-supplementation with omega-3 FAs and vitamin E increases the levels of NO and TAC, while MDA levels decrease compared to placebo. However, the results showed no significant alterations on GSH concentrations, CAT, and SOD activities., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Omega-3 fatty acids (omega-3 FAs) supplementation effects on oxidants and antioxidants are always controversial. Oxidative stress (OS) is one of the major mechanisms that contribute to the pathogenesis of several chronic diseases. The present systematic review and meta-analysis aimed to summarize the finding of randomized clinical trials (RCTs) examining the effects of omega-3 FAs on OS markers. Five databases including PubMed, Embase, Scopus, Web of science, and Cochrane were searched up to May 5th, 2019 with no language restriction. RCTs included if they compared OS indices among subjects who received omega-3 FAs supplements and subjects who supplemented with placebo. To estimate the effects of omega-3 FAs supplementation, standardized mean difference (SMD) with 95% confidence intervals (95% CI) were pooled using random effects model. Of 5,887 publications, 39 trials involving 2,875 participants were included for the meta-analysis. The pooled analysis of data indicated that omega-3 FAs significantly increased serum total antioxidant capacity (TAC) (SMD: 0.48, 95% CI: 0.23, 0.72, P< 0.001; I 2 = 60%), glutathione peroxidase (GPx) (SMD: 0.73, 95% CI: 0.30, 1.16, P= 0.001; I 2 = 83%) activity and decreased malondialdehyde (MDA) (SMD= -0.42, 95% CI: -0.62, -0.21; P < 0.001; I 2 = 74%) compared to the placebo group. However, the effects of omega-3 FAs on nitric oxide (NO) (SMD: -0.17 , 95% CI: -0.77, 0.43, P = 0.57; I 2 = 91%), reduced glutathione (GSH) (SMD= 0.23, 95% CI= -0.17, 0.64, P= 0.25; I 2 = 75%), superoxide dismutase (SOD) (0.12 , 95% CI: -0.40, 0.65, P= 0.64; I 2 = 89%) and catalase (CAT) (0.16, 95% CI: -0.33, 0.65, P= 0.52; I 2 = 75%,) activities was not significant. Supplementation with omega-3 FAs significantly improves MDA, TAC levels, and GPx activity. Thus, omega-3 FAs can be mentioned as enhancer factors in antioxidant defense against reactive oxygen species (ROS)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This paper presents an efficient numerical method to solve fractional infinite-horizon optimal control problems, where the dynamic control system depends on Caputo fractional derivatives. First, by a suitable change of variable, we transform the fractional infinite-horizon optimal control problem to a finite-horizon one. Then, with the help of an approximation, we replace the Caputo derivative to integer order derivative. According to the Pontryagin minimum principle (PMP) for optimal control problems and by constructing an error function, we define an unconstrained minimization problem. In the optimization problem, we use trial solutions for state, costate and control functions where these trial solutions are constructed by using two-layered perceptron neural network. Some numerical results are introduced to explain our main results., (Copyright © 2019 ISA. Published by Elsevier Ltd. All rights reserved.)

Background: The benefits of regular physical activity (PA) are well documented in patients with heart failure (HF), however the amount and intensity of objectively measured PA and sedentary behaviour in HF with preserved (HFPEF) or reduced ejection fraction (HFREF) is not well known., Methods: In a cross-sectional observational study the energy expenditure of 151 participants (HFPEF: n = 53; HFREF: n = 16; at-risk for HF: n = 48; control participants: n = 34) using SenseWear Mini Armbands (Body Media, Inc, Pittsburgh, PA) were monitored. PA outcomes included time spent in different PA intensities (light and moderate-vigorous PA), sedentary time, steps per day, total daily energy expenditure, PA energy expenditure, and the patterns of PA in bouts of ≥ 10 minutes of moderate-vigorous PA., Results: The patients with HFPEF had the lowest volume of activity across the 4 groups. After adjusting for covariates, only steps per day remained significantly different across groups (P = 0.0005). A comparison of HFPEF vs HFREF indicated a higher amount of time in bouts of ≥ 10 minutes of moderate-vigorous PA for patients with HFREF (median, 2.4 [interquartile range, 0-13.5] vs 26 [3.7-46.8]; P = 0.0075). In the at-risk group, PA was lower than the recommended levels in the guidelines., Conclusions: Our findings suggest step count as the most robust outcome in evaluating daily PA in this population. Also, patients with HFPEF showed to be the least active group in the HF continuum. Monitoring volume and pattern of PA for those at risk of HF and patients with HFPEF could help to identify sedentary individuals and to develop tailored behavioural interventions for them., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A, is an autosomal recessive disorder characterized by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which causes major skeletal and connective tissue abnormalities and affects multiple organ systems. In this study, one MPS IVA patient with a severe form from consanguine large Iranian family has been investigated. To find a mutation, all of the 14 exons and intron-exon junctions of GALNS gene were sequenced. Sequencing results were analyzed using bioinformatic analysis in order to predict probable pathogenic effect of the variant. One novel homozygous missense mutation in exon 5, c.542A>G (p.Y181C), was found in the proband. That was predicted as being probably pathogenic by bioinformatics analysis. Segregation and familial study confirmed this pathogenic mutation. In conclusion, we have identified the novel mutation responsible for MPS IVA in an Iranian patient to assist in the diagnosis, genetic counseling and prenatal diagnosis of the affected families., (Copyright © 2015 Elsevier B.V. All rights reserved.)