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Gehan F Balata,1 Ebtessam A Essa,1,2 Hanan A Shamardl,3,5 Samira H Zaidan,4 Mohammed AS Abourehab1,6 1Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Department of Pharmacology, 4Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 5Department of Pharmacology, Faculty of Medicine, El Fayoom University, 6Department of Pharmaceutics, Faculty of Pharmacy, El-Minia University, Egypt Abstract: Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17–99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of –2.24 to –15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities for resveratrol delivery. Keywords: resveratrol, self-emulsifying, olive oil, Tween 80, propylene glycol

In this study, depression severity was defined by the Patient Health Questionnaire (PHQ-9) and five machine learning algorithms were applied to classify depression severity in the presence of diabetes mellitus (DM), cardiovascular disease (CVD), and hypertension (HT) utilizing oxidative stress (OS) biomarkers (8-isoprostane, 8-hydroxydeoxyguanosine, reduced glutathione and oxidized glutathione), demographic details, and medication for eight hundred and thirty participants. The results show that the Random Forest (RF) outperformed other classifiers with the highest accuracy of 92% in a 4-class depression classification when considering all OS biomarkers along with DM, CVD and HT. RF also achieved the highest accuracy of 91% in 3-class classification when studying depression in presence of DM only and an accuracy of 88% and 87% in 5-class classification when investigating depression with CVD and HT, respectively. Moreover, RF performed best in the 3-class depression model with an accuracy of 85% when examining depression severity in the presence of OS biomarkers only. Our findings suggest that depression severity can be accurately identified with RF as a base classifier and that OS is a major contributor to depression severity in the presence of comorbidities. Biomarker analysis can supplement DSM-5-based diagnostics as part of personalized medicine and especially as point of care testing has become available for many of the given OS biomarkers.Clinical Relevance- Depression is the most common form of psychiatric disorder that has an oxidative stress etiology. Current diagnosis relies primarily on the Diagnostic and Statistical Manual for Mental Disorders (DSM-5), which may be too general and not informative for optimal multi-comorbidity diagnostics and treatment. Understanding the role of oxidative stress associated with depression can provide additional information for timely detection, comprehensive assessment, and appropriate intervention of depression illness.

Background: Obesity is a complex disease with underlying genetic, environmental, psychological, physiological, medical, and epigenetic factors. Obesity can cause various disorders, including cardiovascular diseases (CVDs), that are among the most prevalent chronic conditions in Qatar. Recent studies have highlighted the significant roles of the gut microbiome in improving the pathology of various diseases, including obesity. Thus, in this study, we aimed to investigate the effects of dietary intake and gut microbial composition in modulating the risk of CVD development in obese Qatari adults., Methods: We enrolled 46 adult subjects (18-65 years of age) who were classified based on their CVD risk scores, calculated using the Framingham formula, into a CVD no-risk group (score of <10%, n = 36) and CVD risk group (score of ≥10%, n = 10). For each study subject, we measured the gut microbial composition with a 16s rDNA sequencing method that targeted the v3-v4 region using Illumina Miseq, and their nutritional status was recorded based on 24-h dietary recall. Dietary intake, bacterial taxa summary, diversity index, microbial markers, pathway analysis, and network correlation were determined for the study subjects., Results: The CVD risk group showed a lower intake of vitamin D, reduced relative abundance of genera Ruminococcus and Bifidobacterium , no change in bacterial diversity, and higher levels of taurine, hypotaurine, and lipoic acid metabolism than the CVD no-risk group. Besides, the relative abundance of genus Ruminococcus was positively correlated with the intake of protein, monounsaturated fat, vitamin A, and vitamin D., Conclusion: Taken together, our results suggest that the genus Ruminococcus could be used as a microbial marker, and its reduced relative abundance could mediate the risk of CVDs in the Obese Qatari population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lakshmanan, Al Zaidan, Bangarusamy, Al-Shamari, Elhag and Terranegra.)

Background: Failure to prevent rebleeding after cerebral subarachnoid hemorrhage (SAH) is the most frequent reason for high morbidity and mortality of aneurysmal SAH. Our study aims to identify the outcome after surgical clipping of aneurysmal SAH before and after the establishment of the neurovascular unit. The clarifications of the positive turnover in the outcome will be discussed., Methods: A retrospective cohort analysis was carried out on our experience with a controlled group of patients who underwent clipping for ruptured cerebral aneurysms ( n = 61) from January 2015 to December 2019. A modified Rankin scale (mRS) was used to determine the outcome after 6 months of follow-up., Results: The median mRS score (i.e., outcome) on admission was 4, whereas it was with a median score of 2 six months after clipping ( P ≤ 0.001). Overall, the cases with a good outcome were 63.9% of the sample, while the poor outcome conditions were 36.1%. The most cases with an improved outcome were after introducing the neurovascular unit, representing a transition of aneurysmal clipping practice in our center. The good outcome was changed from 42% to 76.7%, and the poor outcome was changed from 58% to 23.3% ( P = 0.019). The crude mortality rate was similar to the rate worldwide (18%), with a noticeable decrease after organizing a neurovascular subspecialty., Conclusion: The outcome after clipping of ruptured SAH can be largely affected by the surgeon's experience and postoperative intensive care. Organizing a neurovascular team is one of the major factors to achieve good outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH., Competing Interests: JK has stock ownership in Bristol-Myers Squibb, Johnson & Johnson, Medtronic, Merck and Pfizer. J-PG was employed by the company Caprion Inc. (now CellCarta). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 El-Far, Durand, Turcotte, Larouche-Anctil, Sylla, Zaidan, Chartrand-Lefebvre, Bunet, Ramani, Sadouni, Boldeanu, Chamberland, Lesage, Baril, Trottier, Thomas, Gonzalez, Filali-Mouhim, Goulet, Martinson, Kassaye, Karim, Kizer, French, Gange, Ancuta, Routy, Hanna, Kaplan, Chomont, Landay and Tremblay.)

Autoimmune diseases comprise a wide group of diseases involving a self-response of the immune system against the host. The etiopathogenesis is very complex involving disease-specific factors but also environmental factors, among which the diet. Maternal diet during pregnancy as well as early nutrition recently attracted the interest of the scientists as contributing to the immune programming. In this paper, we reviewed the most recent literature on the effect of maternal diet and early nutrition in modulating the immune system in a selected subset of autoimmune diseases: type 1 diabetes, celiac disease, inflammatory bowel disease, juvenile idiopathic arthritis and rheumatoid arthritis. Particularly, we focused our narrative on the role of maternal and perinatal nutrition in the epigenetic mechanisms underlying the auto-immune response. Maternal diet during pregnancy as well as breastfeeding and early nutrition play a big role in many epigenetic mechanisms. Most of the nutrients consumed by the mother and the infant are known exerting epigenetic functions, such as folate, methionine, zinc, vitamins B12 and D, fibers, casein and gliadin, and they were linked to gene expression changes in the immune pathways. Despite the common role of maternal diet, breastfeeding and early nutrition in almost all the autoimmune diseases, each disease seems to have specific diet-driver epigenetic mechanisms that require further investigations. The research in this field is opening new routes to establishing a precision nutrition approach to the auto-immune diseases.

In Qatar, Type 1 Diabetes mellitus (T1DM) is one of the most prevalent disorders. This study aimed to explore the gut microbiome's relation to the continuous subcutaneous insulin infusion (CSII) therapy, dietary habits, and the HbA1c level in the pediatric T1DM subjects in Qatar. We recruited 28 T1DM subjects with an average age of 10.5 ± 3.53 years. The stool sample was used to measure microbial composition by 16s rDNA sequencing method. The results have revealed that the subjects who had undergone CSII therapy had increased microbial diversity and genus Akkermansia was significantly enriched in the subjects without CSII therapy. Moreover, genus Akkermansia was higher in the subjects with poor glycemic control (HbA1c > 7.5%). When we classified the subjects based on dietary patterns and nationality, Akkermansia was significantly enriched in Qataris subjects without the CSII therapy consuming Arabic diet than expatriates living in Qatar and eating a Western/mixed diet. Thus, this pilot study showed that abundance of Akkermansia is dependent on the Arabic diet only in poorly controlled Qataris T1DM patients, opening new routes to personalized treatment for T1DM in Qataris pediatric subjects. Further comprehensive studies on the relation between the Arabic diet, ethnicity, and Akkermansia are warranted to confirm this preliminary finding.

Background: A review of the literature has revealed that the rates of overweight and obesity have been increasing in Australia over the last two decades and that wellness mobile phone apps play a significant role in monitoring and managing individuals' weight. Although mobile phone app markets (iTunes and Google Play) list thousands of mobile phone health apps, it is not always clear whether those apps are supported by credible sources. Likewise, despite the prevailing use of mobile phone apps to aid with weight management, the usability features of these apps are not well characterized., Objective: The research explored how usability taxonomy could inform the popularity of downloaded, socially focused wellness mobile phone apps, in particular weight loss and diet apps. The aim of the study was to investigate the Australian mobile phone app stores (iTunes and Google Play) in order to examine the usability features of the most popular (ie, most downloaded) wellness apps., Methods: The design of this study comprises 3 main stages: stage 1, identifying apps; stage 2, development of weight loss and diet evaluation framework; and stage 3, application of the evaluation framework. Each stage includes specific data collection, analysis tools, and techniques., Results: The study has resulted in the development of a justified evaluation framework for weight loss and diet mobile phone apps. Applying the evaluation framework to the identified apps has shown that the most downloaded iTunes and Google Play apps are not necessarily the most usable or effective. In addition, the research found that search algorithms for iTunes and Google Play are biased toward apps' titles and keywords that do not accurately define the real functionality of the app. Moreover, the study has also analyzed the apps' user reviews, which served as justification for the developed evaluation framework., Conclusions: The analysis has shown that ease of use, reminder, bar code scanning, motivation, usable for all, and synchronization are significant attributes that should be included in weight loss and diet mobile phone apps and ultimately in potential weight loss and diet evaluation frameworks.

Aims: To assess the effects of four- and six-point acupuncture on facial sensory detection thresholds to thermal and electrical stimuli., Methods: Ten healthy volunteers underwent four-point acupuncture at ST6 and LI4 bilaterally for 15 minutes. A further 10 subjects underwent six-point acupuncture by adding needling at ST2 bilaterally. Sensory testing to thermal and electrical stimuli applied to mental and infraorbital nerve dermatomes was performed at baseline, 10 minutes, 1 hour, and 1 day after needling., Results: In the mental and infraorbital nerve dermatomes, six-point acupuncture significantly increased warm threshold by a peak mean of 1.1°C to 1.4°C (repeated measures ANOVA P = .001) and this effect was significant at all time points relative to baseline (P < .05). No significant effects were observed by the four-point acupuncture on warm thresholds, and neither four- nor six-point acupuncture significantly altered electrical detection thresholds., Conclusion: A dose effect, related to the number of points employed, may be present when employing acupuncture.

Objective: This study aimed to confirm the location and degree of compromise of the subclavian vessels within the thoracic outlet during ipsilateral arm abduction in patients with clinical evidence of thoracic outlet syndrome and to identify both the physical and physiologic source of neurovascular compromise that induces the symptoms of thoracic outlet syndrome., Design: After a neuromuscular and vascular examination, all of the subjects underwent a two-part high-resolution computed tomographic angiography with three-dimensional reformation. The initial study was performed with the arm held at the side in an anatomical neutral position. Subsequently, the arm was abducted to 90 degrees with external rotation (ABER). In each position, 60 ml of iodinated nonionic contrast medium was injected in the opposite arm at 4 ml/sec. Three-dimensional volume-rendered images were obtained. Each image was subsequently reviewed by a musculoskeletal radiologist (S. Yadavalli). Patients were initially evaluated in the physiatrist's private office (M.M. LaBan). The computed tomographic scans were obtained from the participants as outpatients in an academic community-based medical center (William Beaumont Hospital). Seventeen outpatients with clinical signs and symptoms of thoracic outlet syndrome were evaluated, including seven men and ten women. This group has an average age of 48 yrs (range, 17-73 yrs)., Results: The level of vessel occlusion varied in the costoclavicular space as well as in demonstrating the alterations in the diameter of both the subclavian artery and vein both in the neutral and ABER positions. The possible levels of occlusions included the costoclavicular space, the interscalene triangle, and the retropectoralis minor space. The narrowing of the subclavian vessel was considered significant if the percentage change of the vessel's diameter between the neutral and the ABER positions was 30% or greater for the subclavian artery and 50% or greater for the subclavian vein., Conclusions: The average change in the costoclavicular space between the neutral and ABER positions was 18.2 mm or 55.6%. The degree of subclavian artery occlusion was significant in 8 (47%) of the 17 patients. The average change in artery diameter was 28% (5.5 to 7.5 mm). Significant subclavian vein occlusion was present in 12 (75%) of 16 patients. The average change in venous diameter was 54.1% (5.7 to 12.6 mm). In two cases, venous occlusion occurred in the retropectoralis minor space, one of which was significant at 79%. The vast majority of patients, that is, 13 (76.5%) of 17, demonstrated a compression of either the subclavian vein or artery, whereas 6 (35.3%) of 17 demonstrated a compression in both. In each of these cases, the asymptomatic side failed to demonstrate a significant change in either the venous and/or arterial caliber.

Crosses and backcrosses were carried out with two commercial varieties of turkeys (Black Bronze and White Ross). The birds of the White Ross strain had higher body weights at 12 and 16 weeks of age than the Black Bronze turkeys. The F 1 crosses were intermediate between the body weights of the parent varieties. For the 12-week body weight, heritability estimates were 0.62, 0.74, and 0.68 on the basis of the sire, dam, and sire plus dam components, respectively. The h2 values for the 16-week body weight were 0.55, 1.06, and 0.80, respectively. The estimates of maternal effects were 0.03 and 0.13 for the 12- and 16-week body weights.