Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

Magmas inhibition as a potential treatment strategy in malignant glioma

Journal of Neuro-Oncology - Magmas (mitochondria-associated protein involved in granulocyte–macrophage colony-stimulating factor signal transduction) is a nuclear gene that encodes the...     

Targeting autophagy reverses de novo resistance in homologous recombination repair proficient breast cancers to PARP inhibition

Background Poly(ADP-ribose) polymerase inhibitors (PARPi) target tumours defective in homologous recombination (HR). Most BRCA-wild-type (WT) HR-proficient breast cancers are intrinsically resistant to PARP inhibitors, e.g., talazoparib. We evaluated the role of autophagy in this de novo resistance and determined the underlying mechanism to overcome this.Methods Autophagosome formation and autophagic flux were assessed by evaluating endogenous LC3-II levels and ectopic expression of EGFP-LC3 and mRFP-EGFP-LC3 in breast cancer cells. Autophagy-defective cells were generated by genetic depletion of BECN1, ATG5, p62/SQSTM1 and LAMP1 by using CRISPR-Cas9 double nickase system. The response of PARPi was evaluated in autophagy-proficient and -defective breast cancer cells and in xenograft SCID-mice model.Results Pro-survival autophagy was significantly enhanced upon talazoparib treatment in BRCA-WT breast cancer cell lines. Autophagy-deficient cells were hypersensitive to talazoparib. Targeting autophagy synergistically enhanced the therapeutic efficacy of talazoparib in BRCA1-WT breast cancer cells in vitro and in vivo xenograft tumour mouse model. Mechanistically, autophagy inhibition by chloroquine promoted deleterious NHEJ mediated DSB-repair, leading to extensive genomic instability and mitotic catastrophe.Conclusions Autophagy confers de novo resistance to PARP inhibitor, talazoparib. Autophagy inhibition improves the therapeutic outcome of PARPi treatment in preclinical mice model, bearing HR-proficient breast tumours, warranting its usage in the clinical settings.Subject terms: Breast cancer, Cancer therapy     

Long-term incidence and risk factors of cardiovascular events in Asian populations: systematic review and meta-analysis of population-based cohort studies

Background: Scientific studies on cardiovascular disease (CVD) burden and risk factors are predominantly based on short-term risk in Westerner populations, and such information may not be applicable to Asian populations, especially over the longer term. This review aims to estimate the long-term (>10 years) CVD burden, including coronary heart disease (CHD) and stroke, as well as associated risk factors in Asian populations.

Methods: PubMed, Embase and Web of Science were systematically searched, and hits screened on: Asian adults, free of CVD at baseline; cohort study design (follow-up >10 years). Primary outcomes were fatal and non-fatal CVD events. Pooled estimates and between-study heterogeneity were calculated using random effects models, Q and I² statistics.

Results: Overall, 32 studies were eligible for inclusion (follow-up: 11–29 years). The average long-term rate of fatal CVD is 3.68 per 1000 person-years (95% CI 2.84–4.53), the long-term cumulative risk 6.35% (95% CI 4.69%–8.01%, mean 20.13 years) and the cumulative fatal stroke/CHD risk ratio 1.5:1. Important risk factors for long-term fatal CVD (RR, 95% CI) were male gender (1.49, 1.36–1.64), age over 60/65 years (7.55, 5.59–10.19) and current smoking (1.68, 1.26–2.24). High non-HDL-c, and β- and γ-tocopherol serum were associated only with CHD (HR 2.46 [95% CI 1.29–4.71] and 2.47 [1.10–5.61] respectively), while stage 1 and 2 hypertensions were associated only with fatal stroke (2.02 [1.19–3.44] and 2.89 [1.68–4.96] respectively).

Conclusions: Over a 10 year?+?follow-up period Asian subjects had a higher risk of stroke than CHD. Contrary to CVD prevention in Western countries, strategies should also consider stroke instead of CHD only.     

Genetic Analysis in Bartter Syndrome from India

Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. Around 150 cases have been reported in literature till now. Mutations leading to salt losing tubulopathies are not routinely tested in Indian population. The authors have done the genetic analysis for the first time in the Bartter syndrome on two cases from India. First case was antenatal Bartter syndrome presenting with massive polyuria and hyperkalemia. Mutational analysis revealed compound heterozygous mutations in KCNJ1(ROMK) gene [p(Leu220Phe), p(Thr191Pro)]. Second case had a phenotypic presentation of classical Bartter syndrome however, genetic analysis revealed only heterozygous novel mutation in SLC12A gene p(Ala232Thr). Bartter syndrome is a clinical diagnosis and genetic analysis is recommended for prognostication and genetic counseling.     

Pin hole nasal prosthesis: a clinical report

Atrophic rhinitis is a debilitating nasal mucosal disease characterized by foul-smelling discharge of crusts and enlargement of the nasal cavity. Numerous surgical and nonsurgical methods have been advocated for its treatment. This article describes a noninvasive technique for partial occlusion of the dilated nasal cavity in a patient with atrophic rhinitis by use of a pinhole nasal prosthesis made from clear acrylic resin.     

Dental caries and oral hygiene status of school children in Davangere related to their socio-economic levels: an epidemiological study

Dental caries and periodontal disease, the most commonly seen disease show striking geographic variation, socio-economic patterns and severity of distribution all over the world. Hence, an attempt has been made to determine the relationship of oral health status with socio-economic status in Davangere town. A total of 2007 children of 13 to 14 years age belonging to both sexes were examined. Type III examination was carried out during the survey. DMFcaries Index and Oral Hygiene Index was used to assess caries experience and oral hygiene status. Prasad's classification was used to know the social classification of the children. It was concluded that dental caries experience and oral hygiene status of children are strongly correlated to socio-economic status.