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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

The purpose of this study was to obtain natural drugs from brown seaweed ( Sargassum crassifolium ) as antiatherosclerosis candidates through the study of hypolipidemic mechanisms of action. Modeling of dyslipidemia rats was carried out by feeding high-fat (HFF) and doses of crude fucoidan 100. 200. 400mg / KgBB. in both treatments measured blood lipid profile levels taken from the orbital sinuses. HE's histopathology. mRNA expression. immunohistochemistry (IHC) with parameters VCAM-1. ICAM-1. and MCP-1 were performed on adipose tissue. as well as liver. Total cholesterol values 51.07-225.2. triglycerides 30.43-115.73. HDL 13.1-24.86 mg/dl and LDL 20.22-189.68 mg/dl. In the treatment of crude fucoidan obtained the result of p value < α (0.05. Histopathological features of adipose tissue after administration of HFF for 60 days resulted in an increase in adipose cell size. and the liver experienced structural damage and inflammation. but after 21 days of treatment the morphological picture of adipose tissue was similar to normal morphology and the liver also decreased in severity and inflammation. The results of histochemical staining after treatment showed a positive staining part on MCP-1. The result of p value < α (0.05) of mRNA expression for administration of 3 treatment doses. A dyslipidemic mouse model with HFF administration for 60 days succeeded in becoming a dyslipidemic rat. and crude fucoidan had hypolipidemic activity. Doses of 100. 200. and 400 mg/KgBB crude fucoidan showed improvement in adipose and liver morphological features of severity and inflammation of dyslipidemic rats and decreased mRNA expression., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest.

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.)

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: Women with epilepsy give birth to fewer children than women without epilepsy. We wished to compare the use of assisted reproductive technology in Norwegian women who have epilepsy with Norwegian women in general., Material and Method: In an international prospective registry study, the purpose of which was to identify the teratogenic effects of antiepileptic drugs, we included a total of 1510 births among Norwegian women who have epilepsy in the period 2000-2017. The women were recruited from 18 hospital neurological departments, and a protocol was completed for each pregnancy with demographic and clinical data. The use of assisted fertility among Norwegian women in general in the same period was retrieved from the medical birth registry., Results: In women with epilepsy, altogether 96 of 1510 births (6.4 %) were a result of assisted reproductive technology, whereas the corresponding figure in the general population in the same period was 285 474 of 1 052 901 (2.7 %) (p<0.001). Among women with epilepsy, the proportion who used carbamazepine in pregnancy was significantly higher among those who conceived using assisted reproductive technology than among those who had become pregnant in the regular manner (p=0.02)., Interpretation: Compared to healthy Norwegian women, the use of assisted reproductive technology was more than twice as high among women with epilepsy. This may be an intimation of reduced fertility among these women.

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.