BackgroundCardiovascular diseases (CVD) mortality has been shown to follow a seasonal pattern. Several studies suggested several possible determinants of this pattern, including misclassification of causes of deaths. We aimed at assessing seasonality in overall, CVD, cancer and non-CVD/non-cancer mortality using data from 19 countries from different latitudes.Methods and FindingsMonthly mortality data were compiled from 19 countries, amounting to over 54 million deaths. We calculated ratios of the observed to the expected numbers of deaths in the absence of a seasonal pattern. Seasonal variation (peak to nadir difference) for overall and cause-specific (CVD, cancer or non-CVD/non-cancer) mortality was analyzed using the cosinor function model. Mortality from overall, CVD and non-CVD/non-cancer showed a consistent seasonal pattern. In both hemispheres, the number of deaths was higher than expected in winter. In countries close to the Equator the seasonal pattern was considerably lower for mortality from any cause. For CVD mortality, the peak to nadir differences ranged from 0.185 to 0.466 in the Northern Hemisphere, from 0.087 to 0.108 near the Equator, and from 0.219 to 0.409 in the Southern Hemisphere. For cancer mortality, the seasonal variation was nonexistent in most countries.ConclusionsIn countries with seasonal variation, mortality from overall, CVD and non-CVD/non-cancer show a seasonal pattern with mortality being higher in winter than in summer. Conversely, cancer mortality shows no substantial seasonality.

IMPORTANCE Individuals with asymptomatic or mild coronavirus disease 2019 (COVID-19) have been reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome coronavirus 2 has been found at very high concentrations in swab and sputum samples from such individuals. OBJECTIVE To estimate the virus levels released from individuals with asymptomatic to moderate COVID-19 into different aerosol sizes by normal breathing and coughing, and to determine what exposure could result from this in a room shared with such individuals. DESIGN, SETTING, AND PARTICIPANTS This mathematical modeling study combined the sizedistribution of exhaled breath microdroplets for coughing and normal breathing with viral swab and sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. Viral data were obtained from studies published as of May 20, 2020. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50 m 3 , the size of a small office or medical examination room. MAIN OUTCOMES AND MEASURES Modeling was used to estimate the viral load emitted by individuals breathing normally or coughing, and the concentrations expected in the simulated room at different ventilation rates. RESULTS The mean estimated viral load in microdroplets emitted by simulated individuals while breathing regularly was 0.0000049 copies/cm 3 , with a range of 0.0000000049 to 0.637 copies/ cm 3. The corresponding estimates for simulated coughing individuals were a mean of 0.277 copies/cm 3 per cough, with a range of 0.000277 to 36 030 copies/cm 3 per cough. The estimated concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7.44 million copies/m 3 from an individual who was a high emitter. However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m 3. CONCLUSIONS AND RELEVANCE In this modeling study, breathing and coughing were estimated to release large numbers of viruses, ranging from thousands to millions of virus copies per cubic meter in a room with an individual with COVID-19 with a high viral load, depending on ventilation and microdroplet formation process. The estimated infectious risk posed by a person with typical viral load who breathes normally was low. The results suggest that only few people with very high viral load pose an infection risk in poorly ventilated closed environments. These findings suggest that strict respiratory protection may be needed when there is a chance to be in the same small room with an individual, whether symptomatic or not, especially for a prolonged period.

Serum UA level was elevated significantly as the number of metabolic components increased. Abnormal TG had the most influence on serum UA. A prospective study is warranted to determine if the prevention or treatment of hyperuricemia affects the development of metabolic syndrome.

Bochud, M. (2019). Effects of short-and long-term exposures to particulate matter on inflammatory marker levels in the general population. Environmental Science and

This study attempted to determine whether any association exists between sick building syndrome (SBS) and indoor carbon dioxide (CO(2)) concentrations. We evaluated SBS among 111 office workers in August and November 2003. The environmental conditions in the office, including CO(2) concentrations, temperature, relative humidity, and fine particulate matter (PM(2.5)), were continuously monitored. The most prevalent symptoms of the five SBS groups were eye irritation and nonspecific and upper respiratory symptoms. The generalized estimating equation (GEE) models show that workers exposed to indoor CO(2) levels greater than 800 ppm were likely to report more eye irritation or upper respiratory symptoms.

Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity. We show that shikonin can instigate RIPK1 (receptor [TNFRSF]-interacting serine-threonine kinase 1)- and RIPK3 (receptor-interacting serine-threonine kinase 3)-dependent necroptosis that is accompanied by enhanced autophagy. Shikonin-induced autophagy can directly contribute to DAMP upregulation. Counterintuitively, among the released and ectoDAMPs, only the latter were shown to be able to activate the cocultured dendritic cells (DCs). Interruption of autophagic flux via chloroquine further upregulated ectoDAMP activity and resultant DC activation. For potential clinical application, DC vaccine preparations treated with tumor cells that were already pretreated with chloroquine and shikonin further enhanced the antimetastatic activity of 4T1 tumors and reduced the effective dosage of doxorubicin. The enhanced immunogenicity and vaccine efficacy obtained via shikonin and chloroquine cotreatment of tumor cells may thus constitute a compelling strategy for developing cancer vaccines via the use of a combinational drug treatment.

Sexual dysfunction in female hemodialysis patients: A multicenter study.Background. Sexual function is one aspect of physical functioning. Sexual dysfunction, no matter the etiology, could cause distress. In female hemodialysis patients, sexual problems have often been neglected in clinical performance and research.Methods. We conducted this study by use of self-reported questionnaires. A total of 578 female hemodialysis patients in northern Taiwan were included in this study. Demographic data, comorbid diseases, medications in use, biochemical, and hematologic parameters were analyzed. All patients were asked to complete by themselves three questionnaires: (1) the Index of Female Sexual Function (IFSF) to assess sexual function; (2) the Beck Depression Inventory (BDI) (Chinese version) to rate the severity of depressive symptoms; and (3) the 36-item Short Form Health Survey Questionnaire (SF-36, Taiwan Standard Version 1.0) to survey their quality of life.Results. A total of 138 female patients were enrolled into further analysis. The mean age was 48.7 ± 11.2 years old. The mean IFSF score was 24.5 ± 9.3. Age, BDI score, and serum triglyceride levels were the independent factors of dysfunction in each sexual functional dimension. Patients with higher IFSF scores had significantly higher scores in physical functioning and mental health (P = 0.007 and 0.018, respectively). Patients with higher intercourse satisfaction had significantly higher general health scores (P = 0.001). Conclusion.Sexual dysfunction is frequent in the female hemodialysis population. It is strongly associated with increasing age, dyslipidemia, and depression. The subjects with sexual dysfunction had poorer quality of life. The diagnosis and treatment of sexual dysfunction should be included in the clinical assessment.

BACKGROUND: Airborne transmission of SARS-CoV-2 is an important route of infection. For the wildtype (WT) only a small proportion of those infected emitted large quantities of the virus. The currently prevalent variants of concern, Delta (B1.617.2) and Omicron (B.1.1.529), are characterized by higher viral loads and a lower minimal infective dose compared to the WT. We aimed to describe the resulting distribution of airborne viral emissions and to reassess the risk estimates for public settings given the higher viral load and infectivity. METHOD: We reran the Monte Carlo modelling to estimate viral emissions in the fine aerosol size range using available viral load data. We also updated our tool to simulate indoor airborne transmission of SARS-CoV-2 by including a CO2 calculator and recirculating air cleaning devices. We also assessed the consequences of the lower critical dose on the infection risk in public settings with different protection strategies. RESULTS: Our modelling suggests that a much larger proportion of individuals infected with the new variants are high, very high or super-emitters of airborne viruses: for the WT, one in 1,000 infected was a super-emitter; for Delta one in 30; and for Omicron one in 20 or one in 10, depending on the viral load estimate used. Testing of the effectiveness of protective strategies in view of the lower critical dose suggests that surgical masks are no longer sufficient in most public settings, while correctly fitted FFP2 respirators still provide sufficient protection, except in high aerosol producing situations such as singing or shouting. DISCUSSION: From an aerosol transmission perspective, the shift towards a larger proportion of very high emitting individuals, together with the strongly reduced critical dose, seem to be two important drivers of the aerosol risk, and are likely contributing to the observed rapid spread of the Delta and Omicron variants of concern. Reducing contacts, always wearing well-fitted FFP2 respirators when indoors, using ventilation and other methods to reduce airborne virus concentrations, and avoiding situations with loud voices seem critical to limiting these latest waves of the COVID-19 pandemic.