Higher Male Mortality Research Articles

Sex Differences in Long-Term Cardiovascular Outcomes and Mortality After COVID-19 Hospitalization During Alpha, Delta and Omicron Waves

Background: Increased mortality and occurrence of cardiovascular (CV) outcomes during hospitalization and in short-term follow-up for moderate to severe SARS-CoV-2 infection have been associated with male sex, yet data regarding long-term outcomes by sex and COVID-19 variant (Alpha, Delta, and Omicron) are limited. Methods: This prospective study of 4882 patients examines potential differences by sex in the occurrence of primary combined cardiovascular outcomes (CV death, CV hospitalization, myocardial infarction (MI), stroke, pulmonary embolism) as well as secondary outcomes (CV death, cardiovascular hospitalizations, myocardial infarction, stroke, pulmonary embolism) at 18-month follow-up after urgent hospitalization for SARS-CoV-2-associated pneumonia, as well as evaluating for differences during the three COVID-19 waves. Survival rate was analyzed for the entire cohort by sex and SARS-CoV-2 variant and adjusted for age using the multiple Kaplan–Meier method. To compare survival in groups of men and women for each wave, the Gehan–Wilcoxon test was applied with significance p < 0.05. Univariate Cox proportional hazards models were used to search for potential risk factors of CV death at 18-months follow-up separately for men and women in each COVID-19 wave. Results: Men had significantly higher 18-month CV mortality compared to women in the Delta wave (6.13% men vs. 3.62% women, p = 0.017). Although men had higher percentages of all other CV endpoints (excepting pulmonary embolism) at follow-up during the Delta wave, none were significant compared with women, except for the combined CV endpoint (16.87% men vs. 12.61% women, p = 0.017). No significant differences by sex in CV outcomes were seen during the Alpha and Omicron variants. Discrepancies in CV outcomes in demographical data and concomitant disease between the COVID-19 variants of concern existed. Conclusions: Higher male mortality and higher but non-significant incidences of CV outcomes occurred during the Delta wave of the COVID-19 pandemic, with the lowest incidence of CV outcomes observed during the Omicron variant.

Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions

AbstractThe endoplasmic reticulum (ER) is crucial for maintaining calcium balance, lipid biosynthesis, and protein folding. Disruptions in ER homeostasis, often due to the accumulation of misfolded or unfolded proteins, lead to ER stress, which plays a significant role in various diseases, especially cancer. Urological cancers, which account for high male mortality worldwide, pose a persistent challenge due to their incurability and tendency to develop drug resistance. Among the numerous dysregulated biological mechanisms, ER stress is a key factor in the progression and treatment response of these cancers. This review highlights the dual role of aberrant ER stress activation in urologic cancers, affecting both tumor growth and therapeutic outcomes. While ER stress can support tumor growth through pro‐survival autophagy, it primarily inhibits cancer progression via apoptosis and pro‐death autophagy. Interestingly, ER stress can paradoxically aid cancer progression through mechanisms such as exosome‐mediated immune evasion. Additionally, the review examines how pharmacological interventions, particularly with phytochemicals, can stimulate ER stress‐mediated tumor suppression. Key regulators, including PERK, IRE1α, and ATF6, are discussed for their roles in upregulating CHOP levels and triggering apoptosis. In conclusion, a deeper understanding of ER stress in urological cancers not only clarifies the complex interactions between cellular stress and cancer progression but also provides new opportunities for innovative therapeutic strategies.

A study on the effectiveness of (+)-usnic acid as oral toxic sugar bait against adult male and female Anopheles gambiae

BackgroundDespite the application of various tools for the control of vectors of Plasmodium falciparum, malaria remains the major killer disease in sub-Saharan Africa accounting for up to 90% of deaths due to the disease. Due to limitations of the useage of chemical insecticides such as resistance, negative impact on the environment and to nontarget organisms, the World Health Organization (WHO) requires that affected countries find alternative vector control tools. This study evaluated the effectiveness of ( +)-usnic acid (UA) as an insecticide through oral administration to male and female Anopheles gambiae as an alternative or additional active ingredient to be used in toxic sugar bait.Methods( +)-usnic acid was diluted using acetone at 5, 10, and 15 mg/ml concentrations in three replicates. A 5 ml mixture of 2% food dye and 10% sugar using chlorine-free water mixed with the dilutions of the ( +)-usnic acid and negative control was made containing 2% food dye and 10% sugar solution. The preparations were soaked on a ball of cotton wool and placed over the net of a cup. 5 male and 5 non-blood-fed female newly hatched starved An. gambiae Kisumu strain were introduced together into a cup and monitored for knockdown and mortalities after 4, 24 48, and 72 h. The data were analysed using a multiple linear regression model using the lm function, a base R function and a posthoc test were conducted on the significant main effects and interaction terms using the emmeans function from the emmeans R package. All analyses were performed in RStudio using base R (version 4.3.3).ResultsThere was high mortality of both male and female An. gambiae after ingestion of the toxic sugar bait. 15 mg/ml usnic acid caused the highest mortality (50%) within the first 4 h compared to 5 and 10 mg/ml ( +)-UA. There was a decline in the mortality rate with increased exposure time from 24 to 72 h, however, there was a significant difference in mortality at 5, 10 and 15 mg/ml. Acute toxicity was associated with ingestion of 15 mg/ml after 24 h. 72 h post-mortality was lower in all concentrations than in the control. High mortality was observed among females over the first 4 h (60%) compared to males (40%) due to higher feeding rate of the toxic agent. The proportion of dead males and females was equal after 24 h while after 48 h, the proportion of dead males was high.There was a significantly lower mortality rate after 72 h for both males and females (0 to 13.3%). Compared to all the treatments, high mortality of males was observed.ConclusionsThe results of this study indicate that ( +)-UA when administered as oral sugar bait to An. gambiae has insecticidal properties and is a suitable ingredient to be used as a toxic agent in the novel attractive toxic sugar bait for the control of malaria vectors. ( +)-UA may be an alternative active ingredient as toxic bait in the effort to reduce and eliminate the transmission of Plasmodium falciparum in Africa.

Patterns and trends in melanoma mortality in Spain (1999-2022).

To examine melanoma mortality trends in Spanish Autonomous Communities from 1999 to 2022, focusing on gender and age differences. Data from the National Statistics Institute were used to calculate age-standardized mortality rates (ASMRs). Joinpoint regression identified trend changes. Melanoma mortality varied significantly by region, gender, and age. Eastern Spain had higher male mortality, while western regions had lower rates. Asturias had higher female mortality, with lower rates in Andalusia, Extremadura, and Castilla-La Mancha. Men generally exhibited higher ASMRs than women, with variations across regions. While ASMRs remained stable in most areas, Madrid experienced a notable decline (AAPC: - 1.3%). A national trend reversal occurred in 2014 (AAPC: - 1.3%). For individuals aged 45-74 years, Catalonia saw a significant decrease (AAPC: - 1.1%, p < 0.05), whereas Andalusia experienced an increase (APC: 2.1% since 2007). Nationally, ASMRs for this age group declined (AAPC: - 0.7%). Among those aged 75 years and over, ASMRs varied considerably, with increases observed in Andalusia and Aragon. Nationally, male ASMRs rose (AAPC: 1.6% per year), while female rates were stable. Regional disparities were evident, with higher female mortality in the Balearic Islands and fluctuating rates in the Community of Madrid (an increase followed by a decrease after 2015). The gender gap in mortality varied across regions, with some areas showing a narrowing gap and others widening disparities. Continuous monitoring of melanoma mortality, especially among men and older adults, is crucial. Public health efforts should address regional disparities, improve early detection, and enhance treatment access to optimize outcomes nationwide.

Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan - Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease. This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

Abstract 803: Disparities unveiled: A comprehensive analysis of evolving trends in lung cancer risk factors in the ten most populous countries

Abstract Introduction: Evolving Lung cancer (LC) trends necessitate a continual reassessment of associated risk factors. Methods: We utilized the Global Burden of Disease database to extract Age-Standardized Mortality Rates (ASMR) and risk factor-associated ASMR for Tracheal, Bronchial, and Lung cancer (TBLC) from 1990-2019. The aim was to analyze overall trends along with two pivotal LC risk factors associated trends—tobacco use and air pollution—across ten most populous nations as of 2023 population census. Joinpoint analysis was employed to analyze trends. Results: Globally, TBLC mortality has decreased by 8%, with reductions observed in both tobacco and air pollution-associated mortality. Despite a decrease in male mortality (-17%) and increase in female mortality (+15%), males have exhibited higher mortality for past three decades with M:F ratio of 2.5 in 2019. Similarly, male mortality was higher across all countries. Globally, although tobacco and air pollution-associated mortality has decreased for males and increased for females, both risk factors are linked to significantly higher mortality in males, with M:F ratios of 4.4 and 2.6 for tobacco and air pollution, respectively, in 2019. For tobacco-associated ASMR, China and Indonesia have shown an increase, while China, India, Pakistan, and Nigeria have shown an increase for Air pollution-associated ASMR. On evaluating proportional ASMR, tobacco and air pollution have overall shown a reduction, indicating an increase in other or non-risk factor-related mortality. Conclusion: The fluctuating trends in tobacco-associated and the concerning rise in air pollution-associated in specific countries underscore the complex interplay of societal and environmental factors in LC mortality. The decline in ASMR associated with established risk factors emphasizes the necessity for focused interventions to tackle the changing molecular characteristics of lung cancer and its associated risk factors. Comparison of risk factor-associated Lung Cancer ASMR (1990 vs 2019) Country(ASMR per 100,000 population) 1990 overall ASMR (N) 1990 Tobacco associated ASMR N (%) 1990 Air Pollution Associated N (%) 2019 overall ASMR(N) 2019 Tobacco associated ASMR N (%) 2019 Air Pollution Associated ASMR N (%) Global 27.3 19.8 (72) 5.6 (20) 25.2 16.7 (66) 4.8 (19) India 7.0 4.2 (60) 2.5 (35) 8.1 4.0 (50) 2.6 (33) China 31.2 20.2 (65) 10.3 (33) 38.7 26.3 (68) 10.7 (28) US 49.4 40 (81) 4.5 (9) 36.1 26.1 (72) 1.5 (4) Indonesia 18.0 10.6 (59) 5.4 (30) 24.4 14.7 (60) 4.6 (19) Pakistan 14.7 10.9 (74) 5.4 (36) 17.2 10.7 (63) 5.5 (32) Nigeria 6.8 2 (29) 2.6 (38) 8.3 1.9 (23) 2.7 (32) Brazil 18.0 13.9 (77) 3.2 (18) 15.8 9.7 (61) 1.5 (10) Bangladesh 9.7 6.9 (71) 3.6 (37) 7.8 4.7 (59) 2.6 (33) Russia 32.4 23.2 (72) 4.4 (13) 22.8 16.6 (73) 1.8 (8) Mexico 15.1 9.6 (63) 3.4 (22) 9.7 4.4 (45) 1.5 (16) Citation Format: Chinmay T. Jani, Samuel A. Kareff, Harpreet Singh, Ana Salazar Zetina, Gilberto Lopes. Disparities unveiled: A comprehensive analysis of evolving trends in lung cancer risk factors in the ten most populous countries [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 803.

Secular trends of asthma mortality in China and the United States from 1990 to 2019.

Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US. The deaths, and mortality rates of asthma in China and the US during 1990-2019 were obtained from the Global Burden of Disease Study 2019. The age-period-cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated. In 1990-2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively. In 1990-2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Geographical disparities in hepatitis b virus related hepatocellular carcinoma mortality rates worldwide from 1990 to 2019.

This study aims to evaluate global trends in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) related mortality over the past 30 years. Despite improvements in the treatment of both HBV and HCC, disparities in access to care and treatment persist, and these disparities may have affected HBV-HCC outcomes across certain global regions disproportionately. Using data from the Global Burden of Diseases, Injury, and Risk Factors Study (GBD) from 1990 to 2019, we evaluated overall mortality rates related to HBV-HCC. From 1990 to 2019, overall global HBV-HCC mortality rate decreased by 30.3%. While most world regions experienced declines in HBV-HCC mortality, several regions also experienced significant increases in mortality, including Australasia, Central Asia, and Eastern Europe. When stratified by age, all age groups demonstrated declines in HBV-HCC mortality from 1990 to 2019. Similar trends were observed for both men and women. When stratified by world regions, HBV-HCC mortality in 2019 was highest in East Asia, which was significantly higher than the region with the next highest HBV-HCC mortality, Southeast Asia. Significant disparities in HBV-HCC mortality are observed among global regions. We observed higher HBV-HCC mortality rates with older age, higher mortality in males, and highest mortality in East Asia. The clinical significance of these findings are to highlight those regions that need more targeted resources to improve HBV testing and treatment to reduce the long term consequences of untreated HBV, such as HCC.

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with foetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71%, with higher mortality in males. Death occurred at a median age of 1.2 months (1 week-9 years), due to respiratory failure, cardiac arrest or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival.

DIFFERENCES IN THE ACUTE AMMONIA TOXICITY BETWEEN SEXES OF GUPPY &lt;i&gt;Poecilia reticulata&lt;/i&gt; (POECILIIDAE)

This study evaluated the sensitivity of male and female of guppies (Poecilia reticulata) to ammonia. LC50-96h for males, females and combined sexes of P. reticulata was 37.33, 48.34, and 42.45 mg/L of total ammonia or 1.03, 1.34, and 1.17 mg/L of un-ionized ammonia. The mortality at the concentration of 40 mg/L of total ammonia differed between the sexes with higher mortality in males. These results have implications for production systems, since recommendations of ammonia toxicity reference values that do not consider the difference between the sexes, can lead to the mortality of males, and cause economic losses because males have higher commercial value in the ornamental market.

СОЦИАЛЬНЫЕ ФАКТОРЫ СМЕРТНОСТИ МУЖСКОГО НАСЕЛЕНИЯ: РОССИЯ НА МИРОВОМ ФОНЕ

The subject of the study is to assess the mortality rate of the male population in Russia. The purpose of the study is, based on current statistics, to identify the country’s global position in terms of male mortality and the nature of the impact of social fac- tors on it. The relevance of assessing the mortality rate of Russian men against a global background is determined by the urgent need to attract public attention to this issue, which has an impact on the problem of limited labor resources and conscription potential of the country, on the growth of social production, and provokes many social problems associated with the loss of a breadwinner. The scientific novelty is determined by an integrated approach to the study of the factors of high mortality among men while simultaneously identifying the country’s position in global rankings of the state of human potential. The paper used general logical, analytical, statistical and cartographic methods. An attempt has been made to comprehensively consider the causes of high male mortality in Russia. The authors focused on identifying the social factors of this phenomenon. Research results: it was found that the country has taken a leading position in the world in terms of the gap in life expectancy between men and women, and the specific values of male mortality (per 1000 men of all ages) raise the country to the ninth place in the world. Almost 9% of Russian men do not live to be 40, and 35% do not live to be 60. The high mortality rate of the male population of Russia is a consequence of the mutual influence of many factors. However gender differences in mortality from external causes are especially large (five times). The authors conclude that Russian men experience double pressure from social factors of early mortality - complex economic reality and traditional society with its idea of “post-Soviet masculinity”, in the construction of which alcohol, smoking, and neglect of one’s own health played a major role. One of the main tasks today is to turn our attention to the problems of adult men,and to begin to perceive them as a vulnerable social group that also requires support from the state.

Population mortality in the central Russia municipalities

The Central Federal District (CFD) is the most populous district in Russia, as of the beginning of 2021, 27% of the Russian population lived out there. However, the CFD mortality rate is characterized by a significant variation across different territories of the District. The purpose of this study is to assess the CFD territorial differentiation of mortality rate based on life expectancy with a breakdown on municipalities in 2010-2019. Life expectancy by CFD municipality and urban district was based on information about population size of the CDF municipalities and urban districts, obtained from the database on municipalities for the period 2010-2020 and individual non-personalized Rosstat (Federal State Statistics Service) data on cause-of-death mortality. A total of 326 municipalities and 63 urban districts were included in the analysis. A total of 11.5 thousand life tables were developed. The analysis shows a significant differentiation of mortality rate at the municipal level. Even though the CFD life expectancy is above the Russian average mainly due to high levels of life expectancy in Moscow, the vast majority of the CFD municipalities report a life expectancy below the Russian average. The worst situation with mortality in the CFD is developed in municipalities with a population of less than 10 thousand people. The main factor for a high gap in life expectancy across territories and gender is a high male mortality in working ages. There are significant reserves of for life expectancy growth within the CFD. These reserves are concentrated in the regional capitals with adjacent municipalities, as well as other large municipalities with a population over 100 thousand people.

Life-history traits and fitness of plateau pika (Ochotona curzoniae) in alpine meadow ecosystem.

Plateau pika (Ochotona curzoniae) is an endemic mammal living in the alpine meadow ecosystem in Qinghai–Tibet Plateau. We studied life history of plateau pika by mark–recapturing method. The research results showed that fitness of plateau pika to its habitat was lower than those of many other mammal species; plateau pika adopted quick growth strategy; the life‐history features of plateau pika were accorded with Charnov (Evolutionary Ecology Research, 2002, 4, 749)'s formula about life‐history classification, that is, E/α ≈ 1.35, C·E ≈ 1.7, I/m ≈ 0.3, in which E stands for average adult life span; α stands for age at first reproduction; C is reproductive effort; I is the size of an offspring at independence from the parent; m is average adult body mass. There does not exist dimorphism in plateau pikas. The configurations of females and males are similar; the average body mass of males is a little heavier than that of females, but the difference is not significant (F = 1.0854, df = 154, p > .3058). The juveniles exhibit a J‐form growth curve before 30‐day age and grow slower between 30 and 65‐day age and reach body mass equilibrium at about 65 days old. So, 65 days is the maturity age of plateau pika. There are 3 mortality peaks in plateau pika population. The first time is in neonate period, when only one half of juveniles can pass through this period, which implies that juvenile period is influenced strongly by natural selection; the second time is in fecundity peak period, which reflects the cost of reproduction; the third time is in the old age of plateau pika, a significant loss occurs during this period, which is the result of natural selection. The average longevity of females is longer than that of males. A female reaches the maximum life span recorded, that is, 931 days. The average longevity of all individuals is 16.33 months ≈ 490 days. The survival rate of females is higher than that of males, which reflects the cost of reproduction and society role of males. It is the outcome of natural selection. The sex ratio of neonates is 1:1; however, the sex ratio of adults is female: male = 1.31:1, which is caused by higher mortality of males over females in life history. Plateau pikas reproduced two times every year. The average gestation period of females is 18–20 days. The average litter size is 4.57 individual. The average body mass of neonates is 9.28 g. The average litter size of adult female plateau pika does not variate with age. Breeding season is between April and June. The reproductive value and fertility of 15–18 months age females are highest. The reproductive value and fertility increased with age before reproductive value and fertility peak age; however, the reproductive value and fertility decreased with age after peak age. The fitness of plateau pika (r = .1125) was lower than that of American pikas (O. princeps) (r = 2.172). The survival rate was the main factor influencing fitness. The dynamic trend of plateau pika population was coincident with r, that is, the plateau pika population was stable.

Sex-dependent selection, ageing, and implications for "staying alive".

Incorporating theoretic insights from ageing biology could advance the "staying alive" hypothesis. Higher male extrinsic mortality can weaken selection against ageing-related diseases and self-preservation, leading to high male intrinsic mortality. This may incidentally result in female-biased longevity-promoting traits, a possibility that will require rigorous testing in order to disentangle from the adaptive self-preservation hypothesis presented in the target article.

Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19.

Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses gives that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells can lead to more significant inflammation, proposing an explanation for the monotonic increase of COVID-19 mortality with age and higher mortality for males. We propose that T cells play a crucial role in the immunity against COVID-19, which provides a new direction–improvement of T cell number for advancing current prevention and treatment.

Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study

The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34–2.06-fold lower in males than females (P = 0.018 − < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

COVID-19 Hospitalization and Death: A Retrospective Cohort Study of 238,000 Patients in Brazil

Background: The COVID-19 pandemic has overwhelmed the healthcare system in many countries, and bed availability has become a concern. In this context, the present study aims to analyze the hospitalization and ICU time in patients diagnosed with COVID-19.Methods: The study covers 55,563 ICU admissions and 238,075 hospitalizations in Brazilian Health System units, from February 22, 2020, to June 7, 2021. All patients had a positive diagnosis for COVID-19. For each patient, the presence of symptoms were analyzed: fever, dyspnea, low saturation (SpO2Findings: The average stay was 14.4 days for hospitalization and 12.4 days for ICU. For hospitalizations, the highest Hazard mean values, with a positive correlation, were dyspnea 1.249 (95% CI, 1.225 to 1.273) and saturation 1.157 (95% CI, 1.137 to 1.178). In the ICU, the highest Hazards were respiratory discomfort 1.194 (95% CI, 1.161 to 1.227) and abdominal pain 1.100 (95% CI, 1.047 to 1.156). The survival decreases on average 2.27%/day (Hospitalization) and 3.27%/day (ICU). Survival by age group curves indicates that younger groups are more resistant to prolonged hospital stays than the older group.Interpretation: The hospitalization is lower in younger patients. There is higher mortality in males. Symptoms related to the respiratory tract are associated with a more extended hospital stay.Funding Information: None.Declaration of Interests: None.

Estrogen Receptor Modulators in Viral Infections Such as SARS-CoV-2: Therapeutic Consequences.

COVID-19 is a pandemic respiratory disease caused by the SARS−CoV−2 coronavirus. The worldwide epidemiologic data showed higher mortality in males compared to females, suggesting a hypothesis about the protective effect of estrogens against severe disease progression with the ultimate end being patient’s death. This article summarizes the current knowledge regarding the potential effect of estrogens and other modulators of estrogen receptors on COVID-19. While estrogen receptor activation shows complex effects on the patient’s organism, such as an influence on the cardiovascular/pulmonary/immune system which includes lower production of cytokines responsible for the cytokine storm, the receptor-independent effects directly inhibits viral replication. Furthermore, it inhibits the interaction of IL-6 with its receptor complex. Interestingly, in addition to natural hormones, phytestrogens and even synthetic molecules are able to interact with the estrogen receptor and exhibit some anti-COVID-19 activity. From this point of view, estrogen receptor modulators have the potential to be included in the anti-COVID-19 therapeutic arsenal.

Overwintering and migration behaviour of post‐spawned Atlantic salmon Salmo salar in a large hydropower‐regulated river and reservoir

Tracking 47 post-spawned adult Atlantic salmon Salmo salar L. in a hydropower-regulated river through autumn, winter and spring revealed that winter survival was 56% and 75% in two study years, respectively, with higher mortality of males than females (50% vs. 33% and 100% vs. 13%, respectively). Some kelts (n=7) displayed nondirected movements that were interpreted as a reconditioning period for an average of 9-17 days prior to directed downstream movements indicating the initiation of migration. Survival after the initiation of migration in spring was 83% and 94% to the hydropower dam in the first and second study years, and decreased to 60 and 63%, respectively, after dam passage. There were no further losses in the downriver reach in the second year, with the first year having a cumulative survival estimate of 53% to the river mouth. Kelts approached the dam when the spillway gates were available as a passage option most of the time (64%-75%), but some kelts arrived at the dam or had not yet passed when spillways were closed (n=6) and the only remaining passage option was restricted to the turbines. However, all but one kelt that must have passed via turbine were successful in reaching the river mouth. Migratory delay presumably due to searching behaviour caused by low water flow was estimated at approximately 6 days as migration rates were significantly slower in the reservoir (median ± s.e. 8.5 ± 2.5km day-1 ) than up- (29.7 ± 5.0km day-1 ) or downriver (22.1 ± 3.1km day-1 ). The proportion of time (median 30%) that kelts spent swimming upstream (searching behaviour) in the reservoir was a significant variable for migration success.

Perfil epidemiológico da mortalidade masculina no Brasil, 2014-2018

A política nacional de atenção à saúde do homem visa integrar à população masculina aos serviços de saúde, pois esse público-alvo não procura com muita frequência atendimento médico em razão dos aspectos culturais, vergonha ou falta de tempo. Assim, temos como problemática a alta mortalidade do sexo masculino. O presente estudo tem como objetivo geral, analisar o perfil epidemiológico da mortalidade masculina, e, como objetivo, especificar e identificar as causas da mortalidade entre os homens, além de descrever o perfil sócio demográfico à faixa etária, cor/raça, escolaridade e as macrorregiões. Esse trabalho se trata de um estudo descritivo, retrospectivo, de abordagem quantitativa. A pesquisa foi realizada com dados disponibilizados no sistema DATASUS no qual foram analisadas as principais causas de óbitos na população masculina entre 2014 a 2018, com fins de identificar e analisar as maiores causas epidemiológicas de óbitos em homens. Os resultados do estudo evidenciam que entre 2014 a 2018 teve 3.607.966 mil óbitos em homens. E que a região sudeste teve o maior percentual de óbitos entre as macrorregiões com 44,11%. Quanto à faixa etária 80 anos ou mais com 21,76%. Com relação cor/raça predominou a branca com 47,67%. Escolaridade que predomina ficou de 1 a 3 anos 23,08%, ignorados com 22,98%. A pesquisa poderá reforçar os dados já obtidos por outros pesquisadores, ou, ainda, demonstrar outros índices ainda não levantados. Conclui-se a maior frequência de mortes masculinas por causas evitáveis, destaca-se a importância de investimentos em promoção da saúde e prevenção de agravos na atenção primária.