Correlates of poor clinical outcomes related to COVID-19 among older people with psychiatric illness - a mixed methods study.

OBJECTIVE: COVID-19 may lead to a range of clinical outcomes among older people with psychiatric and medical conditions. Evidence guiding management of future outbreaks among this vulnerable population in psychiatric hospital settings are sparse. In this study, we examined the correlates of poor clinical outcomes related to COVID-19 and explored the perspectives of COVID-19 survivors hospitalized in psychiatry settings. METHOD: The correlates of poor clinical outcomes related to COVID-19 were examined using a retrospective chart review of 81 older people hospitalized in psychiatry settings. Correlates of clinical outcomes related to COVID-19 were assessed by multiple logistic regression models. In addition, the perspectives of 10 COVID-19 survivors were explored by qualitative interviews. The qualitative data was subject to thematic analysis. RESULTS: Although 25.9% (n = 21) participants were asymptomatic, there was high COVID-19 related mortality (14.8%; n = 12). Vitamin-D deficiency, anticholinergic burden, and isolation policies within psychiatric wards were significantly (p < 0.05) related to COVID-19 related deaths. In qualitative interviews, participants emphasized the importance of strengthening local support networks and making vaccination centers more accessible. CONCLUSIONS: Reducing anticholinergic prescriptions and improving isolation policies may help to mitigate poor clinical outcomes. Future research investigating the impact of vitamin-D supplementation on COVID-19 related outcomes is warranted.

Follow-up household assessment for child unintentional injuries two years after the intervention: A community-based study from Karachi, Pakistan.

BACKGROUND: Unintentional childhood injuries are a growing public health concern, and the home is the most common location for non-fatal injuries in children less than 5 years of age. This study describes the long-term effects of two injury prevention educational interventions for caregivers-an educational pamphlet and an in-home tutorial guide-by comparing the change in the prevalence of home injury hazards before and after the interventions. METHODS: This was a pre- (June and July 2010) and post-study with short-term follow-up (November-December 2010) and long-term follow-up (November 2012- January 2013). Neighborhood one included households that received only educational pamphlets after completing a baseline assessment; neighborhood two included households that received an in-home tutorial guide after completing the baseline assessment and receiving the educational pamphlet. The main outcome of this study was the reduction in home injury hazards for children under 5 years of age. RESULTS: A total of 312 households participated in the long-term phase to compare the effect of the interventions. Between the short-term to long-term follow-up, injury hazards significantly reduced in neighborhood two compared to neighborhood one. These included fall hazards (walker use) (IRR 0.24 [95% CI 0.08-0.71]), drowning hazards (open bucket of water in the courtyard and uncovered water pool) (IRR 0.45 [95% CI 0.85-0.98] and IRR 0.46 [95% CI 0.76-0.94]), burn hazards (iron, water heater within reach of child) (IRR 0.56 [95% CI 0.33-0.78] and IRR 0.58 [95% CI 0.32-0.91]), poisoning hazards (shampoo/soap and medicine within reach of child) (IRR 0.53 [95% CI 0.44-0.77] and IRR 0.7 [95% CI 0.44-0.98]) and breakable objects within reach of child (IRR 0.62 [95% CI: 0.39-0.99]). CONCLUSION: An injury prevention tutorial to caretakers of children supplemented with pamphlets could significantly decrease the incidence of falls, drowning, burns, poisoning, and cut injury hazards for children under 5 years of age in their homes in a low-resource setting. This intervention has the potential to be integrated in existing public health programs, such as Lady Health Visitors (LHVs), to disseminate injury prevention information in routine home health visits.

N-Acetyl Cysteine, Selenium, and Ascorbic Acid Rescue Diabetic Cardiac Hypertrophy via Mitochondrial-Associated Redox Regulators.

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.

Mentha longifolia Alleviates Exogenous Serotonin-Induced Diabetic Hypoglycemia and Relieves Renal Toxicity via ROS Regulation.

Diabetic kidney disease is one of the most common microvascular complications of diabetes mellitus with consequences of diabetic nephropathy. Here we amined to evaluate the nephroprotective potential of methanolic Mentha longifolia (MML) against serotonin-induced hypoglycemia allied toxicity in the rat model of diabetes. Diabetes was induced in rats via alloxan administration and validated by blood glucose level measurement. After that, the animals were treated with serotonin and methanolic extract of Mentha longifolia. Surprisingly, serotonin treatment significantly reduced the glucose levels to hypoglycemic conditions, accompanied by impaired redox defense system, abnormal kidney histopathology, dyslipidemia, and altered level of liver toxicity markers. Interestingly these changes were rescued by the methanolic extract of M. longifolia. The present study suggests that impaired serotonin levels during diabetic conditions may accelerate hypoglycemic allied free radical-dependent abnormalities; however, medicinal plants like M. longifolia can reduce these deleterious effects by scavenging free radicals and their associated toxicity.

Pistacia integerrima alleviated Bisphenol A induced toxicity through Ubc13/p53 signalling.

Exposure to environmental toxicants such as Bisphenol A (BPA) has raised serious health issues globally particularly in developing countries. It is ubiquitously used in the manufacturing of canned food and feeding bottles. BPA generated reactive oxygen species can lead to several diseases including cardiotoxicity. However, the endpoints stimulated in BPA cardiotoxicity yet need to be investigated. The current study was aimed to investigate the underlying molecular pathways which may contribute in revealing the protective effects of Pistacia integerrima against BPA induced oxidative stress. The dose of 100 µg/kg BW of BPA, 200 mg/kg BW P. integerrima, and 4 mg/kg BW melatonin was administered to Sprague Dawley rats. Present results of western blotting and qRT-PCR showed the increased expression of p53, PUMA and Drp1, while downregulation of Ubc13 in heart tissues of BPA treated group whereas the levels were reversed upon treatment with P. integerrima. The role of BPA in heart tissue apoptosis was further confirmed by the increased level of P-p53, cytochrome C and disrupted cellular architecture whereas the P. integerrima has shown its ameliorative potential by mitigating the adverse effects of BPA. Moreover, the oxidant, antioxidant, lipid, and liver markers profile has also revealed the therapeutic potential of P. integerrima by maintaining the levels in the normal range. However, melatonin has also manifested the normalized expression of apoptotic markers, biochemical markers, and tissue architecture. Conclusively, the data suggest that P. integerrima may be a potential candidate for the treatment of BPA induced toxicity by neutralizing the oxidative stress through Ubc13/p53 pathway.

Exploring threatened traditional knowledge; ethnomedicinal studies of rare endemic flora from Lesser Himalayan region of Pakistan

ABSTRACT Himalayas are one among the world biodiversity hotspots harboring many endemic medicinal plants. Despite augmentation in the documentation of ethnopharmacological knowledge of medicinal plant species, information regarding endemic species is still underway. Current paper highlights the traditional medicinal uses of rare endemic and unexplored group of plants having potential for novel chemical constituents with effective pharmacological activities. In total, 142 informants (91 male and 51 female) including seventeen traditional healers were interviewed using semi-structured questionnaire, personal observations and group discussions. Interviews were taken in field or otherwise photographs were shown for identification. Females were interviewed indirectly through male family members. For data analysis, quantitative analytical approach was adopted using ethnopharmacological indices as Relative frequency of citations and Fidelity Level. In total, 38 endemic plant species belonging to nineteen families were utilized by the local inhabitants. Highest number of endemics was belonging to Ranunculaceae (7), followed by Gentianaceae and Rosaceae (4 each) with respect to number of species. Highest number of endemics was used in fever, wound healing, throat infection and tonic (4 species each). Root was the most widely used part (36.17%) in cure of diseases and the leading mode administered was decoction (25.49%). Highest use reports and RFC values were recorded for Pimpinella stewartii (58 citations, 0.41 RFC), Caltha alba var. alba (52 citations, 0.37 RFC). Endemic plant species considerably contribute toward ethnomedicinal knowledge and despite rarity, the communities prefer their utilization. Conservation of endemics is necessary for future availability to the local communities.

Identification and Pharmacological Analysis of High Efficacy Small Molecule Inhibitors of EGF-EGFR Interactions in Clinical Treatment of Non-Small Cell Lung Carcinoma: a Computational Approach.

Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound- AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches.