Alopecia Management Potential of Rosemary-Based Nanoemulgel Loaded with Metformin: Approach Combining Active Essential Oil and Repurposed Drug

Kawthar K Abla,1 Mariam K Alamoudi,2 Gamal A Soliman,2,3 Maged S Abdel-Kader,4,5 Mohammed F Aldawsari,6 Mohammed M Mehanna7,8 1Department of Pharmaceutical Science, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 2Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; 3Department of Pharmacology, College of Veterinary Medicine, Cairo University, Giza, Egypt; 4Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; 5Department of Pharmacognosy, College of Pharmacy, Alexandria University, Alexandria, Egypt; 6Department Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; 7Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese American University, Byblos, Lebanon; 8Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptCorrespondence: Mohammed M Mehanna, Department of Industrial Pharmacy, Alexandria University, Alexandria, Egypt, Email [email protected]: Androgenetic alopecia (AGA) is a multifactorial and age-related dermatological disease that affects both males and females, usually at older ages. Traditional hair repair drugs exemplified by minoxidil have limitations such as skin irritation and hypertrichosis. Thus, attention has been shifted to the use of repurposing drugs. Metformin is an anti-diabetic drug, that can promote hair follicle regeneration via upregulation of the hair-inductive capability. Hence, the current study aims to fabricate a safe and effective nanoemulsion to improve metformin efficacy in targeting AGA.Methods: Rosemary oil was selected as the oily phase due to its ability to increase blood flow and hair growth. Rosemary-based nanoemulsions were statistically optimized by Box-Behnken experimental design, loaded with metformin, and incorporated into a hydrogel to form a nanoemulgel. Metformin-loaded nanoemulsions were assessed for their diametric size, uniformity, zeta potential, and metformin characteristics within the formulated nanosystem. The nanoemulgel was then evaluated in terms of its pH, percentage drug content, and in-vitro release performance. In-vivo study assessed the nanoemulgel’s ability to augment hair growth in rats.Results: The experimental design displayed that using 50%w/w, 20%w/w, and 10%w/w of Cremophor®, Labrafil®, and deionized water, respectively, resulted in nanoemulsion formulation with the smallest globule size (125.01 ± 0.534 nm), unimodal size distribution (PDI=0.103), negative surface charge (− 19.9 ± 2.01 mV) with a spherical morphological structure. Rosemary-based nanoemulgel displayed acceptable physicochemical characterizations namely; a neutral pH value of 6.7± 0.15, high drug content (92.9± 2.3%), and controlled metformin in-vitro release. Besides, the formulated nanoemulgel significantly increased the number of hair follicles in the animal model compared with other controls and tested groups.Conclusion: The designed nanoemulgel is a promising approach for treating androgenic alopecia. Keywords: androgenic alopecia, emulgel, metformin, nanoemulsion, rosemary oil, quality by desig

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Psychometric Properties of the Arabic Version of the Addiction Severity Index (ASI-5): A Cross-Cultural Validation Study in Egypt and Saudi Arabia

Mohamed Abouzed,1 Ahmed Aljadani,2 Amgad Gabr,1 Mohamed Elsheikh,1 Mohamed Saad Almuqahwi,3 Mohamed Fayed Alrashidy,4 Ghali Khalaf Alrashidi,4 Mahmoud Farag Soliman,5 Amal Nasser Altamimi,4 Nida Saleh Alenze,4 Nisrin Elsaadouni6 1Psychiatry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 2College of Medicine, University of Ha’il, Ha’il, Saudi Arabia; 3Erada Mental Hospital, Dammam, Saudi Arabia; 4Erada Mental Hospital, Ha’il, Saudi Arabia; 5Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Psychiatry Department, Faculty of Medicine, Mansoura University, Mansoura, EgyptCorrespondence: Mohamed Abouzed, Psychiatry Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt, Email [email protected]: The Addiction Severity Index (ASI) is a globally recognized tool for assessing substance use disorder (SUD) severity. Despite its widespread use, no validated Arabic version exists. This study aimed to validate the Arabic ASI-5 in Egypt and Saudi Arabia and evaluate its psychometric properties.Methods: : A cross-sectional study recruited 400 participants (200 per country) from inpatient/outpatient SUD treatment centers. The ASI-5 underwent forward-backward translation, pilot testing, and cultural adaptation. Internal consistency (Cronbach’s α), test-retest reliability (Spearman’s ρ), and inter-observer reliability were assessed. Convergent and discriminant validity were evaluated using adjusted Spearman’s correlations.Results: The Arabic ASI-5 demonstrated acceptable internal consistency (α = 0.61– 0.82), with medical (α = 0.78) and psychiatric (α = 0.82) domains showing the highest reliability. Lower consistency in drug (α = 0.62) and legal (α = 0.61) domains reflected cultural and methodological factors. Test-retest (ρ = 0.55– 0.98) and inter-observer reliability (ρ = 0.78– 0.99) were strong. Convergent validity was robust for medical and psychiatric domains (r = 0.70– 0.85).Conclusion: The Arabic ASI-5 is a reliable tool for assessing SUD severity in Arabic-speaking populations. Further refinement of drug and legal domains is recommended to enhance cultural relevance.Keywords: addiction severity index, substance use disorder, cross-cultural validation, psychometric

Platelet-Activating Factor Induces TLR4 Expression in Intestinal Epithelial Cells: Implication for the Pathogenesis of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in neonatal intensive care units, however its pathogenesis is not completely understood. We have previously shown that platelet activating factor (PAF), bacteria and TLR4 are all important factors in the development of NEC. Given that Toll-like receptors (TLRs) are expressed at low levels in enterocytes of the mature gastrointestinal tract, but were shown to be aberrantly over-expressed in enterocytes in experimental NEC, we examined the regulation of TLR4 expression and signaling by PAF in intestinal epithelial cells using human and mouse in vitro cell lines, and the ex vivo rat intestinal loop model. In intestinal epithelial cell (IEC) lines, PAF stimulation yielded upregulation of both TLR4 mRNA and protein expression and led to increased IL-8 secretion following stimulation with LPS (in an otherwise LPS minimally responsive cell line). PAF stimulation resulted in increased human TLR4 promoter activation in a dose dependent manner. Western blotting and immunohistochemical analysis showed PAF induced STAT3 phosphorylation and nuclear translocation in IEC, and PAF-induced TLR4 expression was inhibited by STAT3 and NFκB Inhibitors. Our findings provide evidence for a mechanism by which PAF augments inflammation in the intestinal epithelium through abnormal TLR4 upregulation, thereby contributing to the intestinal injury of NEC

Impact of liver cirrhosis due to chronic hepatitis C viral infection on the outcome of ovarian cancer: a prospective study

BACKGROUND: This study was designed to investigate the impact of liver cirrhosis due to chronic hepatitis C virus (HCV) infection on the disease-free and overall survival of ovarian cancer patients undergoing a standard primary operation followed by standard chemotherapy. Attainment of the operative goals, intra- and postoperative events, possible complications under chemotherapy necessitating the termination of treatment, and the impact of ovarian cancer treatment on liver function were assessed. METHODS: This was a prospective observational study that included only patients with primary epithelial ovarian cancer. Only patients with Child-Turcotte-Pugh classification class A disease were recruited. Patients were divided into two groups according to whether they had liver cirrhosis. All the patients underwent primary debulking surgery followed by 6 cycles of chemotherapy, and were followed-up for 24 months after chemotherapy was completed. RESULTS: We recruited 77 patients, 19 of whom had liver cirrhosis. There were no significant differences between patients with or without liver cirrhosis with respect to tumor stage, histopathological type, tumor grade, or optimal operative debulking. There was no registered liver dysfunction-related mortality in the follow-up period, and there were no statistically significant differences between the groups with respect to disease-free or overall survival (p = 0.719 and p = 0.524, respectively). CONCLUSION: From the results of this study, we conclude that compensated liver cirrhosis (Child-Turcotte-Pugh class A) due to chronic HCV infection affects neither the disease-free nor the overall survival of ovarian cancer patients, regardless of their stage. This study shows that it is possible to treat ovarian cancer patients with cirrhosis caused by HCV infection the same as any other patient; treatment does not have to be adjusted as long as the patients have Class A disease

Exposure to phthalates among premenstrual girls from rural and urban Gharbiah, Egypt: A pilot exposure assessment study

<p>Abstract</p> <p>Background</p> <p>Phthalates have been identified as endocrine active compounds associated with developmental and reproductive toxicity. The exposure to phthalates in premenstrual Egyptian females remains unknown. The objective of this study was to characterize phthalate exposure of a potentially vulnerable population of premenstrual girls from urban and rural Egypt.</p> <p>Materials and methods</p> <p>We collected one spot urine sample from 60 10-13 year old females, 30 from rural Egypt, and 30 from urban Egypt from July to October 2009. Samples were analyzed for 11 phthalate metabolites. Additionally, we collected anthropometrics as well as questionnaire data concerning food storage behaviors, cooking practices, and cosmetic use. Phthalate metabolite concentrations were compared between urban and rural Egyptians as well as to age and gender matched Americans.</p> <p>Results</p> <p>Monoethyl phthalate (MEP), was detected at the highest concentration in urine of Egyptian girls (median: 43.2 ng/mL in rural, 98.8 ng/mL in urban). Concentrations of urinary metabolites of di-(2-ethylhexyl) phthalate and dibutyl phthalate were comparable between Egyptians and age matched US girls. Storage of food in plastic containers was a statistically significant predictor of urinary mono-isobutyl phthalate (MiBP) concentrations when comparing covariate adjusted means.</p> <p>Conclusions</p> <p>Urinary concentrations of phthalate metabolites were similar in Egyptian and US populations, suggesting that phthalate exposure also occurs in developing nations. Dietary intake is likely an important route of exposure to phthalates in both urban and rural populations.</p

Genome-Wide Association Studies of the PR Interval in African Americans

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans

Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization

Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate