Global, regional, and national mortality due to unintentional carbon monoxide poisoning, 2000–2021: results from the Global Burden of Disease Study 2021

Background Unintentional carbon monoxide poisoning is a largely preventable cause of death that has received insufficient attention. We aimed to conduct a comprehensive global analysis of the demographic, temporal, and geographical patterns of fatal unintentional carbon monoxide poisoning from 2000 to 2021. Methods As part of the latest Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), unintentional carbon monoxide poisoning mortality was quantified using the GBD cause of death ensemble modelling strategy. Vital registration data and covariates with an epidemiological link to unintentional carbon monoxide poisoning informed the estimates of death counts and mortality rates for all locations, sexes, ages, and years included in the GBD. Years of life lost (YLLs) were estimated by multiplying deaths by remaining standard life expectancy at age of death. Population attributable fractions (PAFs) for unintentional carbon monoxide poisoning deaths due to occupational injuries and high alcohol use were estimated. Findings In 2021, the global mortality rate due to unintentional carbon monoxide poisoning was 0·366 per 100 000 (95% uncertainty interval 0·276–0·415), with 28 900 deaths (21 700–32 800) and 1·18 million YLLs (0·886–1·35) across all ages. Nearly 70% of deaths occurred in males (20 100 [15 800–24 000]), and the 50–54-year age group had the largest number of deaths (2210 [1660–2590]). The highest mortality rate was in those aged 85 years or older with 1·96 deaths (1·38–2·32) per 100 000. Eastern Europe had the highest age-standardised mortality rate at 2·12 deaths (1·98–2·30) per 100 000. Globally, there was a 53·5% (46·2–63·7) decrease in the age-standardised mortality rate from 2000 to 2021, although this decline was not uniform across regions. The overall PAFs for occupational injuries and high alcohol use were 13·6% (11·9–16·0) and 3·5% (1·4–6·2), respectively. Interpretation Improvements in unintentional carbon monoxide poisoning mortality rates have been inconsistent across regions and over time since 2000. Given that unintentional carbon monoxide poisoning is almost entirely preventable, policy-level interventions that lower the risk of carbon monoxide poisoning events should be prioritised, such as those that increase access to improved heating and cooking devices, reduce carbon monoxide emissions from generators, and mandate use of carbon monoxide alarms.publishedVersio

COVID-19: therapeutic disinformation and intoxications

The new coronavirus pandemic alarmed the world. Misinformation regarding prevention and treatment for safeguarding against this pandemic seemed to be life-threatening along with the spreading pandemic. Public health authorities in the world tried to battle this virtual virus by offering true information and correcting misinformation. However, the public misinformation through social media caused toxicological consequences in some parts of the world which provoked awareness, response, and concern of the public health authorities including the Food and Drug Administration (FDA) and the toxicology community. This study analysed the published literature on therapeutic disinformation during the COVID-19 pandemic and its toxicological effects. The electronic databases searched were Scopus, MEDLINE and Scielo. The used keywords were: “COVID-19”, “misinformation”, “social media”, “public health”, “drug toxicity”, and “education”. Finding new strategies for the prevention and treatment of the coronavirus again stresses the role of public education about true drug information. Hundreds of chemicals were/are being tested to be prophylactic medications or healing drugs for the coronavirus. Therefore, spreading accurate information and editing misinformation can be crucial. In summary, this commentary is going to bring attention to misinformation regarding prevention and treatment for safeguarding against the COVID-19 pandemic and its toxicological consequences and the need for public education on the appropriate use of therapies

Cardiomyocyte-Specific JunD Overexpression Increases Infarct Size following Ischemia/Reperfusion Cardiac Injury by Downregulating Sirt3

Ischemia/reperfusion (I/R) injury in acute myocardial infarction activates several deleterious molecular mechanisms. The transcription factor JunD regulates pathways involved in oxidative stress as well as in cellular proliferation, differentiation, and death. The present study investigated the potential role of JunD as a modulator of myocardial injury pathways in a mouse model of cardiac I/R injury. Infarct size, systemic and local inflammation, and production of reactive oxygen species, as well as cytosolic and mitochondrial apoptotic pathways were investigated in adult males after myocardial I/R. In wild-type (WT) mice, 30 minutes after ischemia and up to 24 hours following reperfusion, cardiac JunD messenger ribonucleic acid expression was reduced while JunB increased. Cardiac-specific JunD overexpressing mice (JunDTg/0 ) displayed larger infarcts compared with WT. However, postischemic inflammatory or oxidative responses did not differ. JunD overexpression reduced Sirt3 transcription by binding to its promoter, thus leading to mitochondrial dysfunction, myocardial cell death, and increased infarct size. On the other hand, JunD silencing reduced, while Sirt3 silencing increased infarct size. In human myocardial autopsy specimens, JunD-positive areas within the infarcted left ventricle staining corresponded to undetectable Sirt3 areas in consecutive sections of the same heart. Cardiac-specific JunD overexpression increases myocardial infarct size following I/R. These effects are mediated via Sirt3 transcriptional repression, mitochondrial swelling, and increased apoptosis, suggesting that JunD is a key regulator of myocardial I/R injury. The present data set the stage for further investigation of the potential role of Sirt3 activation as a novel target for the treatment of acute myocardial infarction

TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: reversal by monoclonal TNFα antibodies

none25Aims: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular (CV) complications, but the molecular mechanism of action is unknown.We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA. Methods and results: Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two TNFα transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time- and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNFα plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly upregulated leading to increased vascular oxLDL uptake and NFκB-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNFα treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNFα treatment restored LOX-1 and ARG2 serum levels in RA patients. Conclusions: Increased TNFα levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NFκB/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNFα treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL and Arg2 levelsmixedAkhmedov, Alexander; Crucet, Margot; Simic, Branko; Kraler, Simon; Bonetti, Nicole R; Ospelt, Caroline; Distler, Oliver; Ciurea, Adrian; Liberale, Luca; Jauhiainen, Matti; Metso, Jari; Miranda, Melroy; Cydecian, Rose; Schwarz, Lena; Fehr, Vera; Zilinyi, Rita; Amrollahi-Sharifabadi, Mohammad; Ntari, Lydia; Karagianni, Niki; Ruschitzka, Frank; Laaksonen, Reijo; Vanhoutte, Paul M; Kollias, George; Camici, Giovanni G; Lüscher, Thomas FAkhmedov, Alexander; Crucet, Margot; Simic, Branko; Kraler, Simon; Bonetti, Nicole R; Ospelt, Caroline; Distler, Oliver; Ciurea, Adrian; Liberale, Luca; Jauhiainen, Matti; Metso, Jari; Miranda, Melroy; Cydecian, Rose; Schwarz, Lena; Fehr, Vera; Zilinyi, Rita; Amrollahi-Sharifabadi, Mohammad; Ntari, Lydia; Karagianni, Niki; Ruschitzka, Frank; Laaksonen, Reijo; Vanhoutte, Paul M; Kollias, George; Camici, Giovanni G; Lüscher, Thomas