FMRP protects the lung from xenobiotic stress by facilitating the integrated stress response.

Stress response pathways protect the lung from the damaging effects of environmental toxicants. Here we investigate the role of the fragile X mental retardation protein (FMRP), a multifunctional protein implicated in stress responses, in the lung. We report that FMRP is expressed in murine and human lungs, in the airways and more broadly. Analysis of airway stress responses in mice and in a murine cell line ex vivo, using the well-established naphthalene injury model, reveals that FMRP-deficient cells exhibit increased expression of markers of oxidative and genotoxic stress and increased cell death. Further inquiry shows that FMRP-deficient cells fail to actuate the integrated stress response pathway (ISR) and upregulate the transcription factor ATF4. Knockdown of ATF4 expression phenocopies the loss of FMRP. We extend our analysis of the role of FMRP to human bronchial BEAS-2B cells, using a 9,10-phenanthrenequinone air pollutant model, to find that FMRP-deficient BEAS-2B cells also fail to actuate the ISR and exhibit greater susceptibility. Taken together, our data suggest that FMRP has a conserved role in protecting the airways by facilitating the ISR. This article has an associated First Person interview with the first author of the paper.

Cause of Death Certification in COVID-19 Deaths.

INTRODUCTION: Appropriate cause of death reporting is vital in the pandemic circumstance for effective planning of the control measures. Accurate reporting and registration of the reason for death are crucial in planning of health programs in turn contributing for the national development. BACKGROUND: All births and deaths occurring across India should be mandatorily registered per the Registration of Births and Deaths Act passed in the year 1969. The act also requires the issuance of cause of death certificate by the doctor attending the departed during his last illness. Data obtained from the cause of death certificate provides cause-specific mortality profile, which is required to analyze the health trends of the population. REVIEW RESULTS: This article discusses the available guidelines on the appropriate documentation of cause of death in the confirmed or suspected coronavirus disease-2019 (COVID-19) infection resulting into death. CONCLUSION: Proper certification of the cause of death leads to better epidemic surveillance. Scrutiny of the clinical sequences from the cause of death certificate is useful to prioritize the allocation of resources for critical care management and to augment our knowledge about underlying causes resulting in mortality from COVID-19. CLINICAL SIGNIFICANCE: Dissemination of available guidelines on proper documentation of the cause of death in confirmed/suspected COVID-19 cases will reduce the errors in cause of death reporting. HOW TO CITE THIS ARTICLE: Veeranna CH, Rani S. Cause of Death Certification in COVID-19 Deaths. Indian J Crit Care Med 2020;24(9):863-867.