Neuropathological Examination of Mice Chronically Exposed to Secondhand Smoke.

INTRODUCTION: Around 21.6-35% of military personnel are smokers, while 12.26% of them have been regularly exposed to second-hand smoke (SHS). Second-hand smoke is considered an important risk factor for neurological diseases because it can induce oxidative stress, DNA damage, and disrupt DNA repair pathways. MATERIAL AND METHODS: The brain of air (sham) or SHS exposed mice was cryoperserved, sectioned, and placed on a glass slide before immunoprobing them with antibodies to observe for oxidative DNA damage (8-oxoG), oxidative DNA repair (8-oxoguanine DNA glycosylase 1, Ogg1; apurinic/apyrimidinic endonuclease, Ape1), and inflammatory (glial fibrillary acidic protein) proteins. RESULTS: Nissl staining of the prefrontal cortex (PFCTX) revealed the presence of dark, shrunken cells, hippocampal thinning, and the presence of activated astrocytes in SHS exposed mice. 8-oxoG staining was also more prominent in the PFCTX and hippocampus (HIPP) of SHS exposed mice. Ogg1 staining was reduced in the PFCTX and CA3 hippocampal neurons of SHS exposed mice, whereas it was more prominent in CA1 and CA4 hippocampal neurons. In contrast, Ape1 staining was more prominent in the PFCTX and the HIPP of SHS exposed mice. CONCLUSIONS: These studies demonstrate that oxidative DNA damage (8-oxoG) was elevated and oxidative DNA repair (Ape1 and Ogg1) was altered in the brain of SHS exposed mice. In addition, activated astrocytes (i.e., glial fibrillary acidic protein) were also observed in the brain of SHS exposed mice. Therefore, SHS induces both oxidative DNA damage and repair as well as inflammation as possible underlying mechanism(s) of the cognitive decline and metabolic changes that were observed in chronically exposed mice. A better understanding of how chronic exposure to SHS induces cognitive dysfunction among military personnel could help improve the combat readiness of U.S. soldiers as well as reduce the financial burden on the DOD and veterans' families.

Behavioral and Cognitive Performance Following Exposure to Second-Hand Smoke (SHS) from Tobacco Products Associated with Oxidative-Stress-Induced DNA Damage and Repair and Disruption of the Gut Microbiome.

Exposure to second-hand Smoke (SHS) remains prevalent. The underlying mechanisms of how SHS affects the brain require elucidation. We tested the hypothesis that SHS inhalation drives changes in the gut microbiome, impacting behavioral and cognitive performance as well as neuropathology in two-month-old wild-type (WT) mice and mice expressing wild-type human tau, a genetic model pertinent to Alzheimer's disease mice, following chronic SHS exposure (10 months to ~30 mg/m3). SHS exposure impacted the composition of the gut microbiome as well as the biodiversity and evenness of the gut microbiome in a sex-dependent fashion. This variation in the composition and biodiversity of the gut microbiome is also associated with several measures of cognitive performance. These results support the hypothesis that the gut microbiome contributes to the effect of SHS exposure on cognition. The percentage of 8-OHdG-labeled cells in the CA1 region of the hippocampus was also associated with performance in the novel object recognition test, consistent with urine and serum levels of 8-OHdG serving as a biomarker of cognitive performance in humans. We also assessed the effects of SHS on the percentage of p21-labeled cells, an early cellular marker of senescence that is upregulated in bronchial cells after exposure to cigarette smoke. Nuclear staining of p21-labeled cells was more prominent in larger cells of the prefrontal cortex and CA1 hippocampal neurons of SHS-exposed mice than in sham-exposed mice, and there was a significantly greater percentage of labelled cells in the prefrontal cortex and CA1 region of the hippocampus of SHS than air-exposed mice, suggesting that exposure to SHS may result in accelerated brain aging through oxidative-stress-induced injury.

Complete surgical myocardial revascularization in patients with declined renal functions: 12-month outcomes.

INTRODUCTION: This retrospective observational study aimed to evaluate the feasibility and effectiveness of complete revascularization coronary artery bypass grafting (CABG) in patients with multi-vessel disease (MVD)-CAD and declined renal functions, addressing the knowledge gap regarding optimal treatment strategies and outcomes in this specific patient population. METHODS: Between 2020 and 2022, a total of 58 patients underwent on-pump coronary artery bypass grafting surgery for complete myocardial revascularization in this study. To assess overall survival, Kaplan-Meier with the log-rank test was conducted for statistical analysis. RESULTS: The mean age of cohort was 60.7. The findings showed a high prevalence of medical conditions such as hypertension (50.0%), diabetes (50.0%), and anaemia (41.4%) among the participants. Intraoperatively, low cardiac output syndrome was reported in 5.2% of cases, while perioperative outcomes indicated a need for transfusions in 53.5% of cases and an in-hospital mortality rate of 3.4%. At the 12-month follow-up, no redo revascularization or renal replacement therapy was required, but cardiac mortality was 5.2% and all-cause mortality was 6.9%. CONCLUSIONS: The study concluded that complete revascularization is safe for these patients and highlights the potential benefits, emphasizing the need for further research in optimizing revascularization techniques for this population.

Thromboembolism in the Complications of Long COVID-19.

SARS-CoV-2 is a +ssRNA helical coronavirus responsible for the global pandemic caused by coronavirus disease 19 (COVID-19). Classical clinical symptoms from primary COVID-19 when symptomatic include cough, fever, pneumonia or even ARDS; however, they are limited primarily to the respiratory system. Long-COVID-19 sequalae is responsible for many pathologies in almost every organ system and may be present in up to 30% of patients who have developed COVID-19. Our review focuses on how long-COVID-19 (3 -24 weeks after primary symptoms) may lead to an increased risk for stroke and thromboembolism. Patients who were found to be primarily at risk for thrombotic events included critically ill and immunocompromised patients. Additional risk factors for thromboembolism and stroke included diabetes, hypertension, respiratory and cardiovascular disease, and obesity. The etiology of how long-COVID-19 leads to a hypercoagulable state are yet to be definitively elucidated. However, anti-phospholipid antibodies and elevated D-dimer are present in many patients who develop thromboembolism. In addition, chronic upregulation and exhaustion of the immune system may lead to a pro-inflammatory and hypercoagulable state, increasing the likelihood for induction of thromboembolism or stroke. This article provides an up-to-date review on the proposed etiologies for thromboembolism and stroke in patients with long-COVID-19 and to assist health care providers in examining patients who may be at a higher risk for developing these pathologies.

Investigating thyroid dysfunction in the context of COVID-19 infection.

COVID-19 is a contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). One of the key features of COVID-19 infection is inflammation. There is increasing evidence pointing to an association between cytokine storm and autoimmunity. One autoimmune disease of interest in connection to COVID-19 is hyperthyroidism. COVID-19 has been shown to decrease TSH levels and induce thyrotoxicosis, destructive thyroiditis, and de novo Graves' disease. It has also been suggested that the immune response against SARS-CoV-2 antigens following vaccination can cross-react through a mechanism called molecular mimicry which can elicit autoimmune reactivity, potentially leading to potential thyroid disease post vaccine. However, if the COVID-19 vaccine is linked to reduced COVID-19 related serious disease, it could potentially play a protective role against post COVID-19 hyperthyroidism (de novo disease and exacerbations). Further studies investigating the complex interplay between COVID-19 or COVID-19 vaccine and thyroid dysfunction can help provide substantial evidence and potential therapeutic targets that can alter prognosis and improve COVID-19 related outcomes in individuals with or without preexisting thyroid disease.

Exploring the role of Nrf2 signaling in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most aggressive glial cell tumors in adults. Although current treatment options for GBM offer some therapeutic benefit, median survival remains poor and does not generally exceed 14 months. Several genes, such as isocitrate dehydrogenase (IDH) enzyme and O6-methylguanine-DNA methyltransferase (MGMT), have been implicated in pathogenesis of the disease. Treatment is often adapted based on the presence of IDH mutations and MGMT promoter methylation status. Recent GBM cell line studies have associated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) expression with high-grade tumors. Increased Nrf2 expression is often found in tumors with IDH-1 mutations. Nrf2 is an important transcription factor with anti-apoptotic, antioxidative, anti-inflammatory, and proliferative properties due to its complex interactions with multiple regulatory pathways. In addition, evidence suggests that Nrf2 promotes  GBM cell survival in hypoxic environment,by up-regulating hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Downregulation of Nrf2 has been shown to improve GBM sensitivity to chemotherapy drugs such as Temozolomide. Thus, Nrf2 could be a key regulator of GBM pathways and potential therapeutic target.  Further research efforts exploring an interplay between Nrf2 and major molecular signaling mechanisms could offer novel GBM drug candidates with a potential to significantly improve patients prognosis.

Post-Operative Atrial Fibrillation: Current Treatments and Etiologies for a Persistent Surgical Complication.

Post-operative atrial fibrillation (POAF) is a persistent and serious surgical complication that occur in 20-55% of cardiac surgery cases. POAF may lead to adverse health outcomes such as stroke, thromboembolism, cardiac arrest, and mortality, and may develop long-term. Patients have a 2-fold increase in mortality risk and spend about 3.7 more days in the hospital and $16,000 more in medical costs during their visit. The mechanisms and risk factors of POAF are still poorly understood, yet a strong foundation of how a disease process occurs is needed to provide the most effective treatment. Current mechanisms that are postulated to contribute to POAF include an increase in sympathetic tone, oxidative stress, local and systemic inflammation, a trigger that induces atrial substrate changes, a driver to sustain POAF, and electrolyte disturbances such as hypomagnesemia. While needing more research, current risk factors include age, male sex, history of myocardial infarction or heart failure, hypertension, diabetes, obesity, and COPD. Treatments mostly include prophylaxis of repurposed drugs such as beta-blockers, statins, oral anticoagulants, antiarrhythmics, and Vitamin D and electrolyte supplementation. Autonomic denervation has also been a promising preventative measure for patients undergoing cardiac surgery. This critical review article provides an up-to-date and comprehensive summary of the pathophysiology of POAF, current clinical risk factors and management for POAF and discusses new pathways for further investigation.