Impact of COVID-19 pandemic on the mental health of university students in the United Arab Emirates: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic had a significant impact on the mental well-being of students worldwide. There is a scarcity of information on the mental health impact of the COVID-19 pandemic on university students in the United Arab Emirates (UAE). This study aimed to investigate the mental health impact of the COVID-19, including depression, anxiety and resilience among a sample of university students in the UAE. METHODS: A cross-sectional study using an online survey was conducted from September to November 2021. The patient health questionnaire (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Connor-Davidson Resilience Scale (CD-RISC-10) were used to assess depression, anxiety, and resilience. The COVID-19 impact was assessed using a list of questions. RESULTS: Only, 798 students completed the survey and were analyzed for this study. Overall, 74.8% of the students were females, 91.2% were never married, and 66.3% were UAE-nationals. Based on PHQ-9 and GAD-7 cut-off scores (≥ 10), four out of ten of the students self-reported moderate to severe depression (40.9%) and anxiety (39.1%). Significantly higher mean PHQ-9 and GAD-7 scores were found among students who were impacted by COVID-19 than those non-impacted (mean PHQ-9 = 9.51 ± 6.39 and 6.80 ± 6.34; p = 0.001, respectively) and (mean GAD-7 = 9.03 ± 6.00 and 8.54 ± 6.02; respectively, p < 0.001). Female students who were impacted by COVID-19 had statistically significant higher depression and anxiety scores (mean PHQ-9 of 9.14 ± 5.86 vs. 6.83 ± 6.25, respectively; p < 0.001) than the non-impacted females (mean GAD-7 of 9.57 ± 6.32 vs. 5.15 ± 3.88, respectively; p = 0.005). Never married students had significantly higher PHQ-9 and GAD-7 scores than ever-married (9.31 ± 6.37 vs. 6.93 ± 5.47, P = 0.003) and (8.89 ± 6.11 vs. 7.13 ± 5.49, respectively; p = 0.017). CONCLUSIONS: The results of this study demonstrate that the COVID-19 pandemic has negatively impacted the mental health of this sample of university students in terms of depression and anxiety. The results highlight the need to adopt culturally appropriate interventions for university students and focus on vulnerable groups.

Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities.

INTRODUCTION: The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. METHODS: The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively. RESULTS: From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound 14b) improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic db/db mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound 14b treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound 14b decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound 14b were associated with the activation of the G-protein-coupled bile acid receptor TGR5. CONCLUSION: Compound 14b exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications.

A prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- first results from India.

BACKGROUND: We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India. METHODS: This continuing prospective observational study (February 2021 to May 2022) enrolled participants ≥18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed. FINDINGS: We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism. INTERPRETATION: COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings. FUNDING: No funding support.

Role of Oxidative Stress and Metal Toxicity in the Progression of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the life-threatening neurodegenerative disorders in the elderly (>60 years) and incurable across the globe to date. AD is caused by the involvement of various genetic, environmental and lifestyle factors that affect neuronal cells to degenerate over the period of time. The oxidative stress is engaged in the pathogenesis of various disorders and its key role is also linked to the etiology of AD. AD is attributed by neuronal loss, abnormal accumulation of Amyloid-ß (Aß) and neurofibrillary tangles (NFTs) with severe memory impairments and other cognitive dysfunctions which lead to the loss of synapses and neuronal death and eventual demise of the individual. Increased production of reactive oxygen species (ROS), loss of mitochondrial function, altered metal homeostasis, aberrant accumulation of senile plaque and mitigated antioxidant defense mechanism all are indulged in the progression of AD. In spite of recent advances in biomedical research, the underlying mechanism of disruption of redox balance and the actual source of oxidative stress is still obscure. This review highlights the generation of ROS through different mechanisms, the role of some important metals in the progression of AD and free radical scavenging by endogenous molecule and supplementation of nutrients in AD.

APOE4 allele in north Indian elderly patients with dementia or late onset depression-a multiple-disease case control study.

The objective of the study was to analyze the frequency of APOE4 allele in elderly patients with Alzheimer's or vascular dementia or depression; compare these to age/sex matched controls; compare the results with established literature and highlight new findings. A single center, multiple disease, case-control study was performed with three case groups- probable AD patients (n=36), vascular dementia patients (n=29) and depression patients (n=20) and with a control group (n=32). APOE genotyping was performed in whole blood samples collected from patients and controls by restriction isotyping using the enzymes AflIII and HaeII. There was significant difference in frequency distribution of E4 allele between the AD (12/72; 16.7%) and control groups (3/64; 4.7%) (P=0.03). However, no significant difference was found in any of the other comparisons. The current study demonstrates absence of a significant association between APOE4 positivity and presence of late-onset depression in the north Indian elderly and reinforces the higher APOE4 prevalence in LOAD patients but not in VD patients. It is the first study of its kind from the northern part of India involving multiple disease groups and lays the framework for larger cohort studies.

New genetic players in late-onset Alzheimer's disease: Findings of genome-wide association studies.

Late-onset Alzheimer's disease (LOAD) or sporadic AD is the most common form of AD. The precise pathogenetic changes that trigger the development of AD remain largely unknown. Large-scale genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in multiple genes which are associated with AD; most notably, these are ABCA7, bridging integrator 1 (B1N1), triggering receptor expressed on myeloid cells 2 (TREM2), CD33, clusterin (CLU), complement receptor 1 (CRI), ephrin type-A receptor 1 (EPHA1), membrane-spanning 4-domains, subfamily A (MS4A) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes. The proteins coded by the candidate genes participate in a variety of cellular processes such as oxidative balance, protein metabolism, cholesterol metabolism and synaptic function. This review summarizes the major gene loci affecting LOAD identified by large GWASs. Tentative mechanisms have also been elaborated in various studies by which the proteins coded by these genes may exert a role in AD pathogenesis have also been elaborated. The review suggests that these may together affect LOAD pathogenesis in a complementary fashion.

Morvan's syndrome-is a pathogen behind the curtain?

Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan's syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India. All the four patients manifested behavioral abnormalities, sleep disturbances, hallucinations, autonomic dysfunction, and clinical signs of peripheral nerve hyperexcitability, mostly as myokymia. Two of the patients had Anti-CASPR2 (contactin-associated protein 2) antibodies. Three of them had electromyography features of peripheral nerve hyperexcitability and only one had elevated cerebrospinal fluid protein level. We hypothesize that Morvan's syndrome and other less characterized autoimmune encephalitis/peripheral nervous system syndromes may have infectious triggers. A possible viral trigger may result in generation of autoantibodies which result in the typical manifestations. We base these hypotheses on the finding of four cases of an orphan disease within a short period of time in a limited geographical distribution.

Implementation and results of an integrated data quality assurance protocol in a randomized controlled trial in Uttar Pradesh, India.

BACKGROUND: There are few published standards or methodological guidelines for integrating Data Quality Assurance (DQA) protocols into large-scale health systems research trials, especially in resource-limited settings. The BetterBirth Trial is a matched-pair, cluster-randomized controlled trial (RCT) of the BetterBirth Program, which seeks to improve quality of facility-based deliveries and reduce 7-day maternal and neonatal mortality and maternal morbidity in Uttar Pradesh, India. In the trial, over 6300 deliveries were observed and over 153,000 mother-baby pairs across 120 study sites were followed to assess health outcomes. We designed and implemented a robust and integrated DQA system to sustain high-quality data throughout the trial. METHODS: We designed the Data Quality Monitoring and Improvement System (DQMIS) to reinforce six dimensions of data quality: accuracy, reliability, timeliness, completeness, precision, and integrity. The DQMIS was comprised of five functional components: 1) a monitoring and evaluation team to support the system; 2) a DQA protocol, including data collection audits and targets, rapid data feedback, and supportive supervision; 3) training; 4) standard operating procedures for data collection; and 5) an electronic data collection and reporting system. Routine audits by supervisors included double data entry, simultaneous delivery observations, and review of recorded calls to patients. Data feedback reports identified errors automatically, facilitating supportive supervision through a continuous quality improvement model. RESULTS: The five functional components of the DQMIS successfully reinforced data reliability, timeliness, completeness, precision, and integrity. The DQMIS also resulted in 98.33% accuracy across all data collection activities in the trial. All data collection activities demonstrated improvement in accuracy throughout implementation. Data collectors demonstrated a statistically significant (p = 0.0004) increase in accuracy throughout consecutive audits. The DQMIS was successful, despite an increase from 20 to 130 data collectors. CONCLUSIONS: In the absence of widely disseminated data quality methods and standards for large RCT interventions in limited-resource settings, we developed an integrated DQA system, combining auditing, rapid data feedback, and supportive supervision, which ensured high-quality data and could serve as a model for future health systems research trials. Future efforts should focus on standardization of DQA processes for health systems research. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02148952 . Registered on 13 February 2014.

UFLC method development and validation of a novel triethylamine containing thiophene S006-830 - an antitubercular molecule and its application to pharmacokinetic and bioavailability studies in SD rats.

A sensitive and selective ultra fast liquid chromatography (UFLC) method has been developed and validated for the determination of a potent and novel antitubercular compound S006-830 in Sprague Dawley (SD) rat plasma. Samples were extracted and processed by protein precipitation method using acetonitrile. Chromatographic separation was achieved on a Phenomenex, Luna C-18 column (3µm, 100mm x 2mm i.d.) under isocratic condition. Detection was performed on UFLC-NEXERA system (LC-30AD, Shimadzu, Kyoto, Japan) with a degasser (DGU-20A), auto-injector (SIL-30AC), fixed with a 100-µL loop. Method was found sensitive and reproducible over a linearity range of 15.6-2000 ng/mL. Recovery of S006-830 and internal standard was found >90% for spiked matrix control and standard quality control plasma samples. This validated method was successfully applied to generate pharmacokinetic profile of S006-830 in SD rats. Oral dose proportionality studies were conducted at 100, 50, 25 mg/Kg dose levels, while an IV study was conducted at 25 mg/Kg dose. There was dose dependent increase in AUC and Cmax indicating S006-830 to exhibit linear pharmacokinetics. S006-830 exhibited favorable bioavailability in the range of 45-55%.

Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics upon Antiepileptic Drugs Co-Administration in SD Rats.

Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs) on an antimalarial candidate 99/411 pharmacokinetic (PK) profile. Method. For this, single oral dose PK drug interaction studies were conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT), Carbamazepine (CBZ), and Gabapentin (GB) in both male and female SD rats, to assess the coadministered and intersexual influences on 99/411 PK profile. Results. Studies revealed that there were no significant alterations in the PK profile of 99/411 upon PHT and CBZ coadministration in both male and female rats, while systemic exposure of 99/411 was significantly increased by about 80% in female rats upon GB coadministration. In terms of AUC, there was an increase from 2471 ± 586 to 4560 ± 1396 ng·h/mL. Overall, it was concluded that simultaneous administration of AEDs with 99/411 excludes the requirements for dose adjustment, additional therapeutic monitoring, contraindication to concomitant use, and/or other measures to mitigate risk, except for GB coadministration in females. These findings are further helpful to predict such interactions in humans, when potentially applied through proper allometric scaling to extrapolate the data.