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Acute high-altitude (HA) exposure can induce several pathologies. Dexamethasone (DEX) can be taken prophylactically to prevent HA disease, but the mechanism by which it acts in this setting is unclear. We studied the transcriptome of peripheral blood mononuclear cells (PBMCs) from 16 subjects at low altitude (LA, 225 m) and then 3 days after acute travel to HA (3500 m) during the India-Leh-Dexamethasone-Expedition-2020 (INDEX2020). Half of the participants received oral DEX prophylaxis 4 mg twice daily in an unblinded manner, starting 1 day prior to travel to HA, and 12 h prior to the first PBMC collection. PBMC transcriptome data were obtained from 16 subjects, half of whom received DEX. The principal component analysis demonstrated a clear separation of the groups by altitude and treatment. HA exposure resulted in a large number of gene expression changes, particularly in pathways of inflammation or the regulation of cell division, translation, or transcription. DEX prophylaxis resulted in changes in fewer genes, particularly in immune pathways. The gene sets modulated by HA and DEX were distinct. Deconvolution analysis to assess PBMC subpopulations suggested changes in B-cell, T-cell, dendritic cell, and myeloid cell numbers with HA and DEX exposures. Acute HA travel and DEX prophylaxis induce significant changes in the PBMC transcriptome. The observed benefit of DEX prophylaxis against HA disease may be mediated by suppression of inflammatory pathways and changing leukocyte population distributions.

Dexamethasone can be taken prophylactically to prevent hypobaric hypoxia-associated disorders of high-altitude. While dexamethasone-mediated protection against high-altitude disorders has been clinically evaluated, detailed sex-based mechanistic insights have not been explored. As part of our India-Leh-Dexamethasone-expedition-2020 (INDEX 2020) programme, we examined the phenotype of control (n = 14) and dexamethasone (n = 13) groups, which were airlifted from Delhi (∼225 m elevation) to Leh, Ladakh (∼3,500 m), India, for 3 days. Dexamethasone 4 mg twice daily significantly attenuated the rise in blood pressure, heart rate, pulmonary pressure, and drop in SaO2 resulting from high-altitude exposure compared to control-treated subjects. Of note, the effect of dexamethasone was substantially greater in women than in men, in whom the drug had relatively little effect. Thus, for the first time, this study shows a sex-biased regulation by dexamethasone of physiologic parameters resulting from the hypoxic environment of high-altitude, which impacts the development of high-altitude pulmonary hypertension and acute mountain sickness. Future studies of cellular contributions toward sex-specific regulation may provide further insights and preventive measures in managing sex-specific, high-altitude-related disorders.

The biological and functional significance of selected Critical Assessment of Techniques for Protein Structure Prediction 14 (CASP14) targets are described by the authors of the structures. The authors highlight the most relevant features of the target proteins and discuss how well these features were reproduced in the respective submitted predictions. The overall ability to predict three-dimensional structures of proteins has improved remarkably in CASP14, and many difficult targets were modeled with impressive accuracy. For the first time in the history of CASP, the experimentalists not only highlighted that computational models can accurately reproduce the most critical structural features observed in their targets, but also envisaged that models could serve as a guidance for further studies of biologically-relevant properties of proteins.

BackgroundThe impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown.MethodsWe analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 ​mmHg or diastolic blood pressure of ≥90 ​mmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 ​mmHg or diastolic blood pressure of ≥80 ​mmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000-2025).ResultsAmong 180,335 participants (33.2% women), the mean age was 40.6 ​± ​14.9 years (41.1 ​± ​15.0 and 39.7 ​± ​14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18-19, 20-44, 45-54, 55-64, 65-74 and ​≥ ​75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines.ConclusionAccording to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.

Objective: To evaluate the neuroprotective effect of cryptotanshinone against cladribine-induced cognitive impairment in rats. Methods: Rats were administered with cladribine (1 mg/kg, p.o.) and cryptotanshinone (10 and 20 mg/kg, i.p.) for four weeks. Behavioral tests such as Morris water maze and elevated plus maze were conducted to check memory impairment caused by cladribine. On day 29, all rats were sacrificed, and the brains were separated for estimation of neuroinflammatory factors, biochemical parameters, neurotransmitters, Aβ(1-42), blood-brain barrier permeability, nuclear factor erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). Results: Treatment with cryptotanshinone dose-dependently enhanced spatial memory, improved the levels of neurotransmitter and antioxidant enzymes, and suppressed proinflammatory cytokine release. Cryptotanshinone also decreased Aβ(1-42) accumulation and increased the levels of Nrf2 and BDNF in the hippocampus. Additionally, the histopathological results showed that cryptotanshinone reduced cladribine-induced neuronal death in the hippocampus. Conclusions: Cryptotanshinone exhibits a promising neuroprotective effect against cladribine-induced cognitive impairment in preclinical studies, and may be a potential phytochemical for the treatment and management of cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction: Drug-induced seizures are a growing problem due to their relatively high prevalence; poor prognosis and a large number of different drugs being associated with the etiology. Although rare, seizures reported with sertraline include myoclonic seizures, partial seizures, and generalized seizures. We report the case of a young female with no prior history of seizures who developed an episode of seizures with possible use of sertraline. Case Report: A 40-year-old female presented with the episode of seizures. On examination, Glassgow Coma Scale score was E1V1M4. Three months earlier, she was diagnosed with intraparenchymal hemorrhage (IPH) with neurological deficits. Levetiracetam was started as prophylactic for seizures. Sertraline was added for concomitant depression. Dose increase of sertraline was done by the psychiatrist due to inadequate response for depression. About 1½ months after the dose increase, she presented with seizures. Conclusion: IPH and neurological deficits could be causative for seizures. However, seizures as an adverse drug reaction of sertraline cannot be ruled out as they occurred after the dose increase of Sertraline. Although rare, one should be watchful for this adverse effect of sertraline. [ABSTRACT FROM AUTHOR]