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Background: There is increasing awareness of the physiological effects of Ramadan intermittent fasting (RIF) in obese subjects. However, there are no data on the effects of RIF on plasma volume changes (ΔPV) in individuals with different body weights. Background and Objectives: This study investigated the effects of RIF on ΔPV in normal-weight (NW) and overweight (OW) adult men, and adult men with obesity (OB) and severe obesity (SO). Materials and Methods: Thirty-two male subjects (32) were divided into four groups (n = 8 per group) according to their body mass index (BMI): normal weight (NW) (BMI < 25 kg/m2; age = 27.4 ± 3.8), overweight (OW) (BMI between 25 and 29.9 kg/m2; age = 26.8 ± 3.7), obese subjects (OB) (BMI between 30 and 34.9 kg/m2; age = 25.6 ± 2.9), and severely obesity (SO) (BMI between 35 and 40 kg/m2; age = 24.0 ± 4.1). Blood samples were collected for 24 h on 4 different occasions, at T0 before the start of the Ramadan month, at T1 15 days after the start of Ramadan, at T2 one day after the end of Ramadan, and at T3 on the 21st day after the end of Ramadan to determine ΔPV. All groups completed their fasting rituals for the 30 days of Ramadan. Results: A significant group × time effect occurred for body mass (p = 0.001; ES = 0.53), BMI (p = 0.001; ES = 0.53), and body fat percentage (p = 0.001; ES = 0.52). Post hoc tests indicated reductions in body mass in OB and SO at T1 (p = 0.03; ES = 0.21 and p = 0.002; ES = 0.12) and T2 (p = 0.03; ES = 0.31 and p = 0.02; ES = 0.23), reductions in BMI in OB and SO at T1 (p = 0.04; ES = 0.35 and p = 0.03; ES = 0.42) and T2 (p = 0.03; ES = 0.52 and p = 0.005; ES = 0.48), and reductions in body fat percentage only in OB AT T1 (p = 0.002; ES = 0.31) and T2 (p = 0.001; ES = 0.17). A significant group × time effect occurred for hematocrit (p = 0.02; ES = 0.34), hemoglobin (p = 0.01; ES = 0.35), and ΔPV (p = 0.02; ES = 0.18). Post hoc tests indicated increases in hematocrit in OB at T2 (p = 0.03; ES = 0.36) and hemoglobin in OB and SO at T1 (p = 0.03; ES = 0.35 and p = 0.002; ES = 0.32) and T2 (p = 0.003; ES = 0.21 and p = 0.002; ES = 0.33). There were also increases in ΔPV in OB at T1 and T2 (p = 0.002; ES = 0.25 and p = 0.003; ES = 0.22) and in SO only at T2 (p = 0.02; ES = 0.37). Contrast analysis indicated that NW was significantly lower than the grand mean of OW, Ob, and SO for all anthropometric and PVV variables (all p < 0.05). Conclusions: The effects of RIF on ΔPV and anthropometric characters was greater in obese individuals compared to normal-weight and overweight participants, suggesting that the improvements in body composition and ΔPV produced by RIF could positively influence obesity.

Background & objectives: Recent evidence suggests that bone morphogenetic proteins (BMPs) are involved in regulating of adipose tissue. This study aimed to evaluate the effect of three resistance training methods on bone morphogenetic protein 2 and lipid profile in obese men. Methods: In a semi-experimental trial, 44 obese men (23-32 years) were selected and randomly divided into four groups, including control, interval resistance training, traditional resistance training and circuit resistance training. Interval, traditional and circuit resistance training performed with an intensity of 50% of maximum repetition and active rest, 3-time sessions per week for 12 weeks. Serum BMP-2 levels were measured using an ELISA kit. Data were analyzed using paired t-test, one-way analysis of variance and Tukey post hoc test at the p

Abstract Background Sending a social norms feedback letter to general practitioners who are high prescribers of antibiotics has been shown to reduce antibiotic prescribing. The 2017-9 Quality Premium for primary care in England sets a target for broad-spectrum prescribing, which should be at or below 10% of total antibiotic prescribing. We tested a social norm feedback letter that targeted broad-spectrum prescribing and the addition of a chart to a text-only letter that targeted overall prescribing. Methods We conducted three 2-armed randomised controlled trials, on different groups of practices: Trial A compared a broad-spectrum message and chart to the standard-practice overall prescribing letter (practices whose percentage of broad-spectrum prescribing was above 10% and who had relatively high overall prescribing). Trial C compared a broad-spectrum message and a chart to a no-letter control (practices whose percentage of broad-spectrum prescribing was above 10% and who had relatively moderate overall prescribing). Trial B compared an overall-prescribing message with a chart to the standard practice overall letter (practices whose percentage of broad-spectrum prescribing was below 10% but who had relatively high overall prescribing). Letters were posted to general practitioners, timed to be received on 1 November 2018. The primary outcomes were practices’ percentage of broad-spectrum prescribing (trials A and C) and overall antibiotic prescribing (trial B) each month from November 2018 to April 2019 (all weighted by the number and characteristics of patients registered in the practice). Results We randomly assigned 1909 practices; 58 closed or merged during the trial, leaving 1851 practices: 385 in trial A, 674 in trial C, and 792 in trial B. AR(1) models showed that there were no statistically significant differences in our primary outcome measures: trial A β = − .199, p = .13; trial C β = .006, p = .95; trial B β = − .0021, p = .81. In all three trials, there were statistically significant time trends, showing that overall antibiotic prescribing and total broad-spectrum prescribing were decreasing. Conclusion Our broad-spectrum feedback letters had no effect on broad-spectrum prescribing; adding a bar chart to a text-only letter had no effect on overall antibiotic prescribing. Broad-spectrum and overall prescribing were both decreasing over time. Trial registration ClinicalTrials.gov NCT03862794. March 5, 2019.

Multiple sclerosis (MS) is associated with an impaired immune system that severely affects the spinal cord and brain, and which is marked by progressive inflammatory demyelination. Patients with MS may benefit from exercise training as a suggested course of treatment. The most commonly used animal models of studies on MS are experimental autoimmune/allergic encephalomyelitis (EAE) models. The present review intends to concisely discuss the interventions using EAE models to understand the effectiveness of exercise as treatment for MS patients and thereby provide clear perspective for future research and MS management. For the present literature review, relevant published articles on EAE animal models that reported the impacts of exercise on MS, were extracted from various databases. Existing literature support the concept that an exercise regimen can reduce the severity of some of the clinical manifestations of EAE, including neurological signs, motor function, pain, and cognitive deficits. Further results demonstrate the mechanisms of EAE suppression with information relating to the immune system, demyelination, regeneration, and exercise in EAE. The role for neurotrophic factors has also been investigated. Analyzing the existing reports, this literature review infers that EAE is a suitable animal model that can help researchers develop further understanding and treatments for MS. Besides, findings from previous animal studies supports the contention that exercise assists in ameliorating MS progression.

Background: Obesity is associated with chronic inflammation in obese subjects, which leads to an increase of inflammatory cytokines. This study aimed to evaluate the effect of different intensity circuit resistance training on levels of interleukin 1 beta and interleukin-10 in obese men. Methods: In a semi-experimental trial during May to August 2020, 44 obese men from Tehran city were selected and randomly divided into 4 groups including 1) control (n=11), 2) low-intensity circuit resistance training (n=11), 3) Moderate intensity circuit resistance training (n=11) and 4) High-intensity circuit resistance training (n=11). Resistance training was performed in different intensities including1) High-intensity circuit resistance training: three sets of 10 repetitions with 80% 1RM 2) Moderate intensity circuit resistance: three sets of 13 repetitions with 60% 1RM and 3) low-intensity circuit resistance training: three sets of 20 repetitions with 40% 1RM, three sessions per week for 12 weeks. Also, the control group had their daily life during the 12-week research period and were prohibited from participating in regular exercise. Serum interleukin-1 beta (IL-1β) and interleukin-10 (IL-10) levels were measured using an ELISA kit. Data were analyzed with covariance analysis at P

Obesity and associated chronic inflammation lead to insulin resistance. The aim of this study was to evaluate the effect of varying intensity circuit resistance training on metabolic and inflammatory markers in obese men. In a semi-experimental trial, 44 obese men were selected and randomly divided into four groups, including 1) Control (n=11), 2) Low-intensity circuit resistance training (n=11), 3) Moderate-intensity circuit resistance training (n=11), and 4) High-intensity circuit resistance training (n=11). Resistance training was performed at different intensities, including 1) High-intensity circuit resistance training (80% 1RM), 2) Moderate-intensity circuit resistance (60% 1RM), and 3) Low-intensity circuit resistance training (40% 1RM), three sessions per week for 12 weeks. Serum levels of Dectin-1, TLR2, TLR4, MyD88 were measured using an ELISA kit. Data were analyzed with covariance analysis at P

Background: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. Method: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with Kerecis® Omega3 Wound™ than with standard of care. Conclusion: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.

Chhaya V Sharma,1 Jamie H Long,2 Seema Shah,1 Junia Rahman,1 David Perrett,3 Samir S Ayoub,4 Vivek Mehta1 1Pain & Anaesthesia Research Centre, St Bartholomew’s and The Royal London Hospitals, Barts Health NHS Trust, London, UK; 2Barts & The London School of Medicine, Queen Mary University of London, London, UK; 3BioAnalytical Science, Barts & The London School of Medicine, Queen Mary University of London, London, UK; 4School of Health, Sport and Bioscience, Medicines Research Group, University of East London, London, UK Abstract: Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404). AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic ­neurons, as well as inhibiting synthesis of PGE2 by COX-2. However, the presence of AM404 in the central nervous system following administration of paracetamol has not yet been demonstrated in humans. Cerebrospinal fluid (CSF) and blood were collected from 26 adult male patients between 10 and 211 minutes following intravenous administration of 1 g of paracetamol. Paracetamol was measured by high-performance liquid chromatography with UV detection. AM404 was measured by liquid chromatography-tandem mass spectrometry. AM404 was detected in 17 of the 26 evaluable CSF samples at 5–40 nmol⋅L–1. Paracetamol was measurable in CSF within 10 minutes, with a maximum measured concentration of 60 μmol⋅L–1 at 206 minutes. This study is the first to report on the presence of AM404 in human CSF following paracetamol administration. This may represent an important finding in our understanding of paracetamol’s mechanism of action, although measured concentrations were far below the previously documented IC50 for this metabolite. Keywords: acetaminophen, paracetamol, paracetamol: mechanism of action, AM404, N-­arachidonoylphenolamine, pharmacology - theories of analgesic action

Background and Objectives: Several studies have reported that some conditions such as exercise and hypoxia induce DNA damage and dysfunction and apoptosis. Some plant foods contain numerous bioactive compounds and anti-inflammatory properties that can help fight DNA damage. Therefore, the current study evaluated the effect of supplementation of Adiantum capillus-veneris (ACV) extract on Bax/B-cell lymphoma 2 (Bcl-2) ratio apoptotic index and remodeling of pulmonary alveolar epithelial cells in lung tissue of healthy Wistar rats during stressful conditions (hypoxia). Materials and Methods: Twenty-seven Wistar male rats (four-week old, 72 ± 9 g) were randomly assigned into three groups: normoxic, sedentary, and not-supplemented (NG, n = 9); exercise and hypoxia and not-supplemented (HE, n = 9); and exercise and hypoxia and supplemented group (HS, n = 9). The NG remained sedentary in the normoxia environment for nine weeks. The HE group participated in a high-intensity (IT) program for six weeks, then remained sedentary in the hypoxia environment for three weeks. The low-pressure chamber simulated a ~2800 M altitude 24 h/d. HS participated in IT, then entered and remained sedentary in the hypoxia environment for three weeks, and they consumed 500 mg per kg of body weight ACV extract. Results: The Bax/Bcl-2 ratio of the HE group increased significantly (+50.27%, p ≤ 0.05), the average number of type I pneumocytes was reduced significantly (−18.85%, p ≤ 0.05), and the average number of type II pneumocytes was increased significantly (+14.69%, p ≤ 0.05). Also, after three weeks of consuming the ACV extract, the HS group in comparison with the HE group had their Bax/Bcl-2 ratio reduced significantly (−24.27%, p ≤ 0.05), the average number of type I pneumocytes increased significantly (+10.15%, p ≤ 0.05), and the average number of type II pneumocytes reduced significantly (−7.18%, p ≤ 0.05). Conclusion: The findings show that after three weeks of hypoxia following six weeks of high-intensity interval training in Wistar rats, the Bax/Bcl-2 ratio and the number of type II pneumocytes were increased and the number of type I pneumocytes was reduced significantly. These results strongly suggest that an apoptosis state was induced in the lung parenchyma, and consuming ACV extract modulated this state.