Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Ion-Triggered In Situ Gelling Intranasal Spray of Dronedarone Hydrochloride Nanocarriers: In Vitro Optimization and In Vivo Pharmacokinetic Appraisal

The current study aims to develop niosomal nanocarriers for intranasal delivery of dronedarone hydrochloride to ameliorate its limited bioavailability. Niosomes were prepared by ethanol injection method and optimized using 3² full factorial experimental design. Both Span® type (X1) and Span®: cholesterol ratio (X2) were set as independent variables. Vesicle size (Y1), polydispersity index (Y2), zeta potential (Y3), and entrapment efficiency (Y4) were set as responses. The optimal formula was further incorporated into an ion-sensitive in situ gelling polymer for intranasal delivery. Optimal formula (N7), which is composed of Span® 80: cholesterol (1:1), was of the least vesicle size (121.27 ± 13.31 nm), least polydispersity index (0.43 ± 0.073), highest zeta potential (−22.23 ± 2.84 mV) and highest entrapment efficiency (73.44 ± 2.8%). About 75.86% and 60.29% of dronedarone hydrochloride were released from N7 dispersion and in situ gel, respectively, within 12 h, compared to only 13.3% released from a drug-free suspension. In vivo pharmacokinetic study on male New Zealand rabbits resulted in significantly higher Cmax, AUC0–72, and AUC0–∞ of intranasal niosomal in situ gel compared to oral suspension. Almost twofold amplification of relative bioavailability was obtained after intranasal administration of niosomal in situ gel (195.7%) compared to oral suspension

Tackling acne vulgaris by fabrication of tazarotene-loaded essential oil-based microemulsion: In vitro and in vivo evaluation

This study aimed to formulate and optimize an anti-acne drug namely tazarotene (TZR) in essential oil-based microemulsion (ME) using either Jasmine oil (Jas) or Jojoba oil (Joj). TZR-MEs were prepared using two experimental designs (Simplex Lattice Design®) and characterized for droplet size, polydispersity index, and viscosity. Further in vitro, ex vivo, and in vivo investigations were performed for the selected formulations. Results revealed that TZR-selected MEs exhibited suitable droplet size, homogenous dispersions, and acceptable viscosity, in addition to spherical-shaped particles in morphology. The ex vivo skin deposition study showed a significant TZR accumulation in all skin layers for the Jas-selected ME over the Joj one. Further, TZR didn't show any antimicrobial activity against P. acnes, however, it was boosted when it was incorporated into the selected MEs. The in vivo study results of the infected mice ears induced by P. acnes revealed that our selected MEs successfully reached a high level of ear thickness reduction of 67.1% and 47.4% for Jas and Joj selected MEs, respectively, versus only 4% for the market product. Finally, the findings confirmed the ability to use essential oil-based ME, particularly with Jas, as a promising carrier for topical TZR delivery in the treatment of acne vulgaris

THE EFFECT OF CO-PROCESSED EXCIPIENTS DURING FORMULATION AND EVALUATION OF PEDIARIC LEVETIRACETAM ORODISPERSIBLE TABLETS IN RATS

Objective: The main aim of this research was to make cost-effective taste-masking oral pediatric orodispersible tablets (ODTs) of Levetiracetam as an antiepileptic drug (AED) using various co-processed excipients by direct compression method. Methods: Eight kinds of ready-made co-processed excipients in addition to sucralose and menthol as a sweetener were utilized. The weight variation, drug content, friability, in-vitro disintegration, dissolution time, hardness, thickness, and pharmacokinetics of the produced ODTs were determined. Results: The optimized formula (F5) containing Pharmaburst® 500 showed the shortest disintegration time (11.66 sec) and more than 98% of Levetiracetam within 10 min(Q10). The Pharmacokinetic study of this optimum formula (F5) in rats using HPLC-UV detector showed 26.904 ± 2.027ng/ml as the Cmax and 101.935 ± 0.894 hr.ng/mL as AUC compared to commercial Tiratam® solution 10.421 ± 0.295ng/ml and 23.135 ± 0.43 hr.ng/mL respectively. Conclusion: Levetiracetam orally orodispersible tablets were successfully prepared with acceptable hardness, satisfactory taste, and rapid disintegration in the oral cavity avoiding first-pass metabolism to yield the desired rapid effect in facing epilepsy for patients who experience dysphagia like pediatric and geriatric. In addition to the unconsciousness of the epileptic patient followed the seizure attack

OPTIMIZING LEVETIRACETAM SURFACTANT-BASED NANOVESICLES (LEV-NVS) GEL FOR TREATING EPILEPSY USING EXPERIMENTAL DESIGN

Objective: To develop and estimate the intranasal delivery of Levetiracetam surfactant-based nanovesicles (Lev-Nvs) as a brain-targeted antiepileptic delivery system prepared via solvent evaporation technique. Methods: Optimized formulation F (OPT) chosen by the Design-Expert® program gave the highest entrapment efficiency (EE%) was  incorporated into the gel. An experimental design was adopted utilizing various (span 65) surfactants and different cholesterol ratios.The (Lev-Nvs) nanovesicles were formulated by solvent evaporation technique and evaluated for in-vitro characterization parameters such as zeta sizer,Transmission Electron Microscopy (TEM), zeta potential .The nasal gel was evaluated for drug-excipient interactions utilizing Fourier Transform Infrared Spectroscopy (FTIR) and subjected to in-vitro and in-vivo release studies, Results: The results indicated that the entrapment efficiency (EE%) of Levetiracetam surfactant-based nano-vesicles (Lev-Nvs) could be modulated by the alterations in surfactant and cholesterol concentrations. Optimized formulation F (OPT) showed an entrapment efficiency of (87.9 ± 1.06 %), (206.7 ± 20.43 nm) particle size, (-34.1) zeta potential and (0.979) PDI. The nanovesicle nasal gels of the F(OPT) were prepared using Carbopol 940 at different concentrations. G 0.375 formulation showed the best in vitro drug release (87.36%) after 12 hrs. Finally, the comparative in vivo pharmaco-kinetics release studies on rats revealed considerable, sustained release of the nanovesicle nasal gel and higher relative bioavailability than an equivalent dose of oral solution (293.85%). Conclusion: Our study proves the improved efficacy of Levetiracetam as a surfactant-based nanovesicle intranasal gel in the brain targeting antiepileptic medication

Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring

In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient’s quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg/kg b.wt), and T2DM-BBR-Vild (10 mg/kg b.wt + Vild (5 mg/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK/mTOR-mediated autophagy and limiting ER stress