cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.

BACKGROUND: Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL. METHODS: Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia. RESULTS: Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products. CONCLUSIONS: A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.

An 8-year observational study of the death places of patients with COPD in Turkey.

AIM: The place of death is one of the indicators of the quality of end-of-life care, which has become an essential public health issue with the aging of the population and the increase in life expectancy. There is a lack of data regarding the location of deaths caused by chronic obstructive pulmonary disease (COPD), the third-leading cause of mortality worldwide. This retrospective, cross-sectional study aimed to investigate the places of death of patients with COPD in Turkey and their trends over the years. METHODS: The study included patients who had a COPD International Classification of Diseases code in the hospital information system and were provided a medication report for this disease in a university hospital's chest diseases outpatient clinic between January 1, 2014, and December 31, 2021. The place and date of death were obtained from the death notification system and recorded as an in-hospital or out-of-hospital death. RESULTS: A total of 1402 (77.3%) patients died in the hospital and 412 (22.7%) died outside the hospital, and when comparing the pandemic period and before, no significant difference was observed between the places of death. Sixty-three (49.6%) of 127 patients over the age of 90 years died outside the hospital, and a significant relationship was observed between advanced age and out-of-hospital mortality (P < 0.005). CONCLUSION: According to our findings, a substantial number of patients with COPD in Turkey die in hospitals. The insufficiency of nursing homes and lack of hospice care cause more hospital deaths. Our data are expected to guide the development of end-of-life care policies for patients with COPD in our country. Geriatr Gerontol Int 2023; 23: 938-944.

Association Between Known Close Contact History and Severity of COVID-19 Pneumonia: A Preliminary Evidence Supporting Importance of Filiation.

OBJECTIVE: The role of a known contact history in coronavirus disease 2019 severity in secondary cases is unknown. The study was aimed to investigate the relationship between the close contact history and the severity of the disease in coronavirus disease 2019 pneumonia. MATERIAL AND METHODS: Hospitalized patients diagnosed with coronavirus disease 2019 pneumonia were included. The demo- graphic, clinical, and laboratory data of the patients were collected retrospectively and patients with or without close contact history were analyzed with respect to the severity of pneumonia. RESULTS: In a total of 100 patients with coronavirus disease 2019 pneumonia, 54 (54%) were male and mean age was 42.28 ±17.13 years. Respiratory rate/min (P = .033) was higher, duration of hospitalization (P = .043) was longer, need for oxygen therapy (P < .001), intensive care unit admission (P = .001), and severe pneumonia (P < .001) were higher in the group without a close contact history (n = 50). Male gender (OR, 4.77; 95% CI, 1.06-21.32; P = .041), not having a close contact history (OR, 4.03; 95% CI, 1.00-16.13;P = .049), non-hospital-associated patients (OR, 9.59; 95% CI, 1.47-62.41; P = .018), and dyspnea (OR, 7.58; 95% CI, 1.64-34.93;P = .009) were found to be risk factors for severe pneumonia. CONCLUSION: Known close contact history was associated with non-severe pneumonia and was found to be an independent predic- tor of disease severity in coronavirus disease 2019 pneumonia. The study provides evidence that filiation may prevent severe disease.