Human Mortality Research Articles

Molecular docking and antibacterial and antibiotic-modifying activities of synthetic chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one in a MepA efflux pump-expressing Staphylococcus aureus strain.

Bacterial resistance has become a global concern for public health agencies. Various resistance mechanisms found in Staphylococcus aureus strains grant this bacterium resistance to a wide range of antibiotics, contributing to the rise in human mortality worldwide. Resistance mediated by efflux pumps is one of the most prevalent mechanisms in multi-resistant bacteria, which has aroused the interest of several researchers in the search for possible efflux pump inhibitors. In view of the aforementioned considerations, it is important that new strategies, such as the synthesis of chalcones, be made available as a viable strategy in antimicrobial therapy. In this study, the synthesized chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one was tested for its antibacterial activity, focusing on antibiotic modification and the inhibition of the MepA efflux pump present in S. aureus strain K2068. The broth microdilution method, using microdilution plates, was employed in microbiological tests to determine the minimum inhibitory concentration of the chalcone, antibiotics, and ethidium bromide. The results show that while the chalcone did not exhibit direct antibacterial activity, it synergistically enhanced the effects of ciprofloxacin and ethidium bromide, as evidenced by the reduction in MICs. In addition, computer simulations of molecular docking demonstrate that the tested chalcone acts on the same binding site as the efflux pump inhibitor chlorpromazine, interacting with essentially the same residues. These data suggest that the chalcone may act as a MepA inhibitor.

Association of Ozone and Temperature with Ischemic Heart Disease Mortality Risk: Mediation and Interaction Analyses.

Global warming and elevated ozone (O3) levels are gradually gaining widespread attention, and exposure to which may cause many physiological changes associated with cardiovascular events such as hypertension, cardiomyocyte apoptosis, etc. In addition, ischemic heart disease (IHD) is the leading cause of death worldwide. However, the contributions of temperature and O3, independently or in combination, to IHD mortality are not well understood. This study employs a two-stage analytical protocol (generalized additive model followed by meta-analysis) to explore the respective associations of temperature and O3 with IHD mortality, and determine their possible mediation and interaction effects. Our results suggest that increases of 10 μg/m3 in O3 and 1 °C in temperature at lag01 day are associated with increased IHD mortality risks of 0.789% and 0.686%, respectively. O3 can mediate the relationship between temperature and IHD mortality, with a pooled estimate of 0.140%, while temperature can mediate the association between O3 and IHD mortality, with a pooled estimate of 0.162%. The additive and multiplicative interaction effects of O3 and temperature were significantly associated with IHD mortality. The study findings demonstrate that higher temperature and O3 concentrations can increase human IHD mortality risk through interaction and mediation effects, providing a scientific basis for the synergistic management of temperature and O3 or associated interventions.

Application of the first exit time stochastic model with self-repair mechanism to human mortality rates.

The purpose of this study is to construct a mortality model that reasonably explains survival curves and mortality rates in terms of the decline in biological function, which is the phenomenon of ageing. In this model, an individual organism is regarded as a collection of subsystems, and for each subsystem, the model defines human mortality by introducing positive self-repair mechanisms and stochastically generated negative external shocks. The probability density function of the time of death is derived explicitly, and the model parameters are estimated using life tables from Japan and the UK, which demonstrate the existence of multiple parameter sets that fit well with the observed data.

Anticancer Drug Development, Pharmaceutical Progress

Anticancer drug development is becoming complex and demanding because human cancer leads to 12% of global human mortality. Chemical and pharmacological breakthroughs play leading roles in updating drug evaluation and development for different types of tumors. Chemical and pharmacological breakthroughs manifest in different facets. A large proportion of financial and workload increases in drug discovery must be paid off. In front of complexity, difficulties, and financial increase of drug development, evaluative promotion must go miniature- wise and single-cell-wise. Multi-omics knowledge and technology are greatly expanded and understood in depth. This type of technical trend is suitable for current experimental exploration and clinical occasions. Technical and pharmacologic advances are especially emphasized to address this trend. Presently, the anticancer pharmaceutical study is multi-faceted and risk-taking. To keep up this momentum, multi-disciplinary drug evaluation, clinical selection, and combination principles should be discovered. Past and futuristic chemical and pharmacological interactions and breakthroughs are discussed. In summary, the landscape of pharmaceutical investigation should be integrated with chemical and pharmacological knowledge in every facet of drug development and clinical personalization.

Activation of the Influenza B M2 Proton Channel (BM2).

Influenza B viruses have cocirculated during most seasonal flu epidemics and can cause significant human morbidity and mortality due to their rapid mutation, emerging drug resistance, and severe impact on vulnerable populations. The influenza B M2 proton channel (BM2) plays an essential role in viral replication, but the mechanisms behind its symmetric proton conductance and the involvement of a second histidine (His27) cluster remain unclear. Here we performed membrane-enabled continuous constant-pH molecular dynamics simulations on wildtype BM2 and a key H27A mutant channel to explore its pH-dependent conformational switch. Simulations captured the activation as the first histidine (His19) protonates and revealed the transition at lower pH values compared to AM2 is a result of electrostatic repulsions between His19 and preprotonated His27. Crucially, we provided an atomic-level understanding of the symmetric proton conduction by identifying preactivating channel hydration in the C-terminal portion. This research advances our understanding of the function of BM2 function and lays the groundwork for further chemically reactive modeling of the explicit proton transport process as well as possible antiflu drug design efforts.

Construction of electrochemical immunosensors based on Au@MXene and Au@CuS nanocomposites for sensitive detection of carcinoembryonic antigen

Cancer is currently one of the major causes of human mortality and has received widespread attention. In this paper, Au@CuS composite nanomaterial as a sandwich immunosensor tag for carcinoembryonic antigen (CEA) detection strategy was studied. Herein, Au@CuS composite nanomaterials were obtained by Au nanoparticles modified with CuS, which were combined with secondary antibody (Ab2) to construct an immunosensor that interacted with H2O2 to produce a current response. The anti-CEA primary antibody (Ab1) was fixed on the glassy carbon electrode (GCE) modified by Au@MXene. The completed electrochemical immunosensor was constructed with rapid detection and high sensitivity for CEA. Under optimal conditions, the linearity ranged from 0.01 pg/mL to 0.5 ng/mL, and the detection limit was 3.8 fg/mL. This tactic possesses good reproducibility, constancy and selectivity. At the same time, this strategy has latent practical value for the test of other tumor markers.

Two amino acid pairs in the Gc Glycoprotein of Severe Fever with Thrombocytopenia Syndrome Virus responsible for the enhanced virulence

Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no fatality. We identified a pair of amino acid residues in the Gc protein, glycine and serine, at residues 581 and 934, respectively, derived from Tk-F123, leading to a fatal infection. Those in Ng-F264 were arginine and asparagine. These results suggest that this pair of residues affects the Gc protein function and regulates SFTSV virulence. Our findings provide useful clues for the elucidation of viral pathogenicity and the development of effective live-attenuated vaccines and antiviral strategies.

Ecological and Reproductive Cycles Drive Henipavirus Seroprevalence in the African Straw-Coloured Fruit Bat (Eidolon helvum).

Bats are known to host zoonotic viruses, including henipaviruses that cause high fatality rates in humans (Nipah virus and Hendra virus). However, the determinants of zoonotic spillover are generally unknown, as the ecological and demographic drivers of viral circulation in bats are difficult to ascertain without longitudinal data. Here we analyse serological data collected from African straw-coloured fruit bats (Eidolon helvum) in Ghana over the course of 2 years and across four sites, comprising three wild roosts and one captive colony. We focus on antibody affinity to five henipavirus antigens: Ghanaian bat henipavirus (GhV), Nipah virus (NiV), Hendra virus (HeV), Mojiang virus (MojV) and Cedar virus (CedV). In the wild roosts, we detected seasonal variations in henipavirus antibody binding, possibly associated with bat life-history cycles and migration patterns. In the captive colony, we identified increases in antibody affinity levels among pregnant bats, suggesting possible shifts in the immune system during pregnancy. These bats then pass maternal antibodies to their pups, which wane before antibody affinity levels rise later in life following initial infections and/or reactivation of latent infections. These results improve our understanding of the links between bat ecology and viral circulation, including for GhV, a locally-circulating African henipavirus.

The role for ω-3 polyunsaturated and short chain fatty acids in hypertension: an updated view on the interaction with gut microbiota

As of 2024, arterial hypertension is still considered the leading modifiable cardiovascular risk factor and, due to high rates of undertreatment and poor blood pressure control, the major contributor to human morbidity and mortality. Development of new treatment options and better interventions in lifestyle correction have become a priority of experimental and clinical research. In the last decades, dietary supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and generation of gut microbiota-derived short chain fatty acids (SCFAs) have surged as potential and promising interventions for hypertension and cardiovascular prevention. ω-3 PUFAs are considered “essential” fatty acids that can be obtained only from dietary sources. Although previous intervention trials were not consistent in reporting a significant benefit of ω-3 PUFAs, the recent REDUCE-IT trial has provided robust evidence in support of their role in cardiovascular prevention. Recent studies have also identified the intestinal microbiota as a potential player in the pathophysiology and progression of hypertension. Although this might occur through many pathways, generation of SCFAs that is highly dependent on dietary fiber intake is primarily involved, providing an additional target for the development of novel therapeutic strategies. For these reasons, some scientific societies currently recommend dietary supplementation of ω-3 PUFAs and fiber-containing foods in patients with hypertension. In this narrative review, we summarize the results of studies that examined the effects of ω-3 PUFAs and SCFAs on blood pressure, highlighting the mechanisms of action on the vascular system and their possible impact on hypertension, hypertension-related organ damage and, ultimately, cardiovascular outcomes.

Au Nanoparticles-Trisbipyridine Ruthenium(II) Nanoaggregates as Signal-Amplifying SERS Tags for Immunoassay of cTnI.

Acute myocardial infarction (AMI) is one of the leading causes of human mortality worldwide. In the early stages of AMI, the patient's electrocardiogram (ECG) may not change, so the fast, sensitive, and accurate detection of the specific biomarker of cardiac troponin I (cTnI) is of great importance in the early diagnosis of AMI. In this work, for the first time, electrostatic nanoaggregates of negatively charged Au nanoparticles and positively charged trisbipyridine ruthenium(II) ions (i.e., (-)AuNPs|[Ru(bpy)3]2+ ENAs) as novel and signal-amplifying surface-enhanced Raman scattering (SERS) tags were synthesized in an easy and rapid (<3 min) way and applied in the highly sensitive, rapid detection of cTnI in human serum by being combined with an immunochromatographic test strip (ICTS). The synthesized (-)AuNPs|[Ru(bpy)3]2+ ENAs exhibited strong SERS activity due to the multiple Raman-active units (three bpy ligands) carried by each [Ru(bpy)3]2+ complex ion and abundant hotspots in each SERS tag. The developed (-)AuNPs|[Ru(bpy)3]2+ ENAs-based SERS-ICTS has been validated to be applicable in detection of cTnI in human serum with excellent sensing performances, such as fast testing (5 min) and a low detection limit (60 pg/mL). It is envisioned that the developed (-)AuNPs|[Ru(bpy)3]2+ ENAs-based SERS-ICTS sensor may have promising applications in point of care testing of various biomarkers in clinic. Additionally, this work may inspire the finding and the application of new types of Raman reporter molecules based on high valent metal-multi ligand coordination compounds like [Ru(bpy)3]2+.

Numerical Treatment for the Caputo-Fabrizio Fractional Smoking Model using an Efficient Numerical Technique

Smoking is a prevalent social behavior widely practiced worldwide, especially in settings such as schools and some significant gatherings. Based on the World Health Organization (WHO), smoking is the third leading source of human mortality and the primary preventable cause of disease. This study introduces a highly efficient simulation technique to analyze and solve the Caputo-Fabrizio (CF) fractional smoking model. We numerically solve the fractional integral equations (FIEs) with Simpson’s 1/3 rule, an effective numerical integration technique. We concentrate on clarifying the stability/convergence of the proposed strategy. We juxtapose the outcomes derived using the Runge-Kutta method (RK4) with those obtained through the implemented methodology. The findings indicate that the used technique provides a simple and efficient instrument for simulating the solution of these models. The principal advantage of the proposed method is its dependence on a limited number of straightforward steps, devoid of long-term consequences or reliance on a perturbation parameter.

Characteristics of pulse wave velocity and its correlation with cardiovascular disease risk factors in healthy individuals.

Cardiovascular disease (CVD) is a major cause of human mortality and has become the leading cause of death worldwide. Existing studies indicate that structural and functional damage to the main arteries represents a significant risk factor for early vascular lesions and many CVDs. This study aimed to explore characteristics of carotid-femoral pulse wave velocity (cfPWV) and its correlation with cardiovascular disease risk factors in healthy individuals. Convenience sampling was used to collect demographics, risk factors, and laboratory examinations from 501 healthy individuals who underwent health checkups at our healthcare center from August 2020 to January 2021. Pearson correlation coefficients were used to examine the correlations between cfPWV and various parameters in both sexes. Multiple linear regression analysis was used to investigate the factors potentially influencing cfPWV. A statistically significant difference in cfPWV between sexes was observed only in the age group of subjects 38-47 years old. The results of the univariate analysis showed that in males, cfPWV was positively correlated with age, blood pressure, heart rate, and alcohol consumption and was negatively correlated with tehe resistive index. In females, cfPWV was positively correlated with age, blood pressure, heart rate, alanine aminotransferase, urea, creatine, uric acid, fasting blood glucose, triglycerides, total cholesterol, and heart rate. The results of multivariable analysis indicated that age, systolic blood pressure, heart rate, and alcohol consumption were influencing factors for cfPWV in males, while age, systolic blood pressure, heart rate, and creatinine were influencing factors for cfPWV in females (P <0.05 for all). In healthy individuals, the distribution patterns of cfPWV values vary by sex and age. In the elderly population, especially elderly women, enhanced monitoring and regular follow-ups are recommended to prevent the development and progression of CVDs in high-risk individuals at an early stage.

Extreme Heat and Specific-Cause Mortality during Summer 2018 in Mainland Portugal

Abstract Climate change has led to increased frequency and duration of extreme heat periods, impacting human health and mortality. During the 2003 heatwave, it was estimated that there were between 25,000 and 70,000 excess deaths in Western Europe. Specific-cause mortality analysis was conducted in Portugal that year and has not been assessed since. The goal of this study is to estimate the impact of an extreme heat period in 2018 on specific-cause mortality in mainland Portugal. An ecological study was conducted comparing observed and expected deaths, from August 2 to 9, 2018, in Portugal. Two comparison periods were chosen: from July 19 to 26, 2018 (C1) and the average deaths from August 2 to 9 in 2017 and 2019 (C2). Excesses, ratios, and respective 95% confidence intervals were calculated in R. Analyses were stratified by sex, age group, and district. Consistent excess deaths were observed between comparators, showing a greater impact in circulatory diseases (C1: 283, 95% CI: 210; 356 and C2: 239, 95% CI: 164; 314) and respiratory diseases (C1: 98, 95% CI: 55; 141 and C2: 95, 95% CI: 52; 138). Regarding death ratios, with C1, the highest death ratios were observed for exposure to excessive natural heat (50.00, 95% CI: 37.11; 65.92) and ischemic stroke (4.00, 95% CI: 2.07; 6.99). With C2, the highest death ratios were observed for exposure to excessive natural heat (50.00, 95% CI 37.11; 65.92) and atherosclerosis (2.71, 95% CI 1.63; 4.24). The excesses and ratios of deaths were higher in more urbanized districts, females, and age groups above 75 years. The results suggest that the extreme heat in 2018 had an impact on mortality. Elevated death ratios and excesses were observed for various causes of death with considerable statistical magnitude and significance. These findings align with other national and international studies. Public health action is increasingly critical to mitigate the observed rise in mortality during periods of extreme heat. Key messages • Specific-cause mortality analysis during extreme heat suggests a greater impact in circulatory and respiratory diseases, in residents of urbanized districts, females, and individuals of 75+ years. • Understanding these specific causes can better inform public health actions and planning, thereby mitigating the adverse effects of extreme heat.

What’s pension got to do with it? Mortality inequality at older ages

Abstract Background The potential role of social protection systems and welfare states for population health and mortality has attracted increased interest in recent decades but mostly focused on overall characteristics or clusters of countries. Moreover, often neglecting older people even though the great majority of all deaths in high-income countries occur at later ages. We focus on the key social protection scheme for old adults: the generosity of the level of pensions. We compare pensions based on previous work history to basic minimum pensions. Our study is novel both by linking pension system to remaining life expectancy at age 65(LE65+), but also by studying the association to variation in LE65+, since that gives a measure of inequality. We do so across countries and over time. Methods and Materials Our sources of data are from the Human Mortality Database and the Social Policy Indicator Database. Data for OECD countries are matched over a long period of time and analysed by pooled time-series regression analyses with fixed effects. Results Although the results indicate that the generosity of pensions based on both pervious work history and basic minimum income our results primarily show the importance of basic minimum income. Here the effect sizes are larger and especially for women than for men (0.149*** vs. 0,.0715***). Concerning the variation in LE (65+) we find that more generous basic pensions are associated with reduced variation for women -4.64e-05**. Conclusions We provide new insights in how pension policies potentially influence mortality among older persons especially by extending our analyses also to inequality in mortality. Our results points to the importance of basic pensions. The gendered division of labour is a plausible explanation for the findings and to have an adequate pension for all should be of primary concern for public health. Key messages • Adequate basic pension for all of importance for remaining life expectancy among older people. • Adequate basic pension for all of importance for reducing mortality inequality among women.

Author Correction: Attributing human mortality from fire PM2.5 to climate change

Author Correction: Attributing human mortality from fire PM2.5 to climate change

Interferon as an immunoadjuvant to enhance antibodies following influenza B infection and vaccination in ferrets

Despite annual vaccination, influenza B viruses (IBV) continue to cause significant morbidity and mortality in humans. We have found that IBV infection resulted in a weaker innate and adaptive immune response than influenza A viruses (IAV) in ferrets. To understand and overcome the weak immune responses to IBV in ferrets, we administered type-I or type-III interferon (IFN) to ferrets following infection or vaccination and evaluated their effects on the immune response. IFN signaling following viral infection plays an important role in the initial innate immune response and affects subsequent adaptive immune responses. In the respiratory tract, IFN lambda (IFNL) has regulatory effects on adaptive immunity indirectly through thymic stromal lymphopoietin (TSLP), which then acts on immune cells to stimulate the adaptive response. Following IBV infection or vaccination, IFN treatment (IFN-Tx) upregulated gene expression of early inflammatory responses in the upper respiratory tract and robust IFN, TSLP, and inflammatory responses in peripheral blood cells. These responses were sustained following challenge or vaccination in IFN-Tx animals. Serum IFNL and TSLP levels were enhanced in IFN-Tx animals following challenge/rechallenge over mock-Tx; however, this difference was not observed following vaccination. Antibody responses in serum of IFN-Tx animals following IBV infection or vaccination increased more quickly and to higher titers and were sustained longer than mock-Tx animals over 3 months. Following rechallenge of infected animals 3 months post treatment, antibody levels remained higher than mock-Tx. However, IFN-Tx did not have an effect on antibody responses following challenge of vaccinated animals. A strong direct correlation was found between TSLP levels and antibody responses following challenge-rechallenge and vaccination-challenge indicating it as a useful tool for predicting adaptive immune responses following IBV infection or vaccination. The effects of IFN on strengthening both innate and adaptive responses to IBV may aid in development of more effective treatments following infection and improved influenza vaccines.

Deep learning assisted cancer disease prediction from gene expression data using WT-GAN

Several diverse fields including the healthcare system and drug development sectors have benefited immensely through the adoption of deep learning (DL), which is a subset of artificial intelligence (AI) and machine learning (ML). Cancer makes up a significant percentage of the illnesses that cause early human mortality across the globe, and this situation is likely to rise in the coming years, especially when non-communicable illnesses are not considered. As a result, cancer patients would greatly benefit from precise and timely diagnosis and prediction. Deep learning (DL) has become a common technique in healthcare due to the abundance of computational power. Gene expression datasets are frequently used in major DL-based applications for illness detection, notably in cancer therapy. The quantity of medical data, on the other hand, is often insufficient to fulfill deep learning requirements. Microarray gene expression datasets are used for training procedures despite their extreme dimensionality, limited volume of data samples, and sparsely available information. Data augmentation is commonly used to expand the training sample size for gene data. The Wasserstein Tabular Generative Adversarial Network (WT-GAN) model is used for the data augmentation process for generating synthetic data in this proposed work. The correlation-based feature selection technique selects the most relevant characteristics based on threshold values. Deep FNN and ML algorithms train and classify the gene expression samples. The augmented data give better classification results (> 97%) when using WT-GAN for cancer diagnosis.

Bioactive Adrenomedullin in Dogs with Sepsis and Septic Shock: A Prospective, Case-Control Study.

Sepsis and septic shock are leading causes of morbidity and mortality in both humans and dogs, and early diagnosis is crucial for improving outcomes. This study aimed to evaluate bioactive adrenomedullin (bio-ADM) concentrations in dogs with septic shock (n = 25), dogs with sepsis without evidence of shock (n = 25), and healthy control dogs (n = 25). Plasma bio-ADM concentrations were measured using a human sandwich enzyme-linked immunosorbent assay and reported as median (interquartile range). Plasma bio-ADM concentrations were significantly higher in both septic groups compared to the healthy controls (all <22.4 pg/mL), but not significantly different between the septic shock (75.0 [28.7-115.0] pg/mL) and sepsis (30.7 [22.4-79.7] pg/mL) groups. Dogs with higher illness severity scores had significantly higher bio-ADM concentrations (93.1 [32.2-122.0] pg/mL) than those with lower scores (29.8 [22.4-71.2] pg/mL). However, bio-ADM concentrations did not differ between survivors (33.0 [22.7-76.7] pg/mL) and non-survivors (74.7 [26.1-123.2] pg/mL). Measurement of bio-ADM is a potential marker for canine sepsis, but not for the identification of septic shock, and may provide information on disease severity. Further studies, including those on non-infectious inflammatory conditions, are necessary to better understand the diagnostic utility of bio-ADM measurement and its potential role as a marker of treatment response in dogs with sepsis.

The role of high mobility group proteins in cellular senescence mechanisms.

Aging is a universal physiological phenomenon, and chronic age-related diseases have become one of the leading causes of human mortality, accounting for nearly half of all deaths. Studies have shown that reducing the incidence of these diseases can not only extend lifespan but also promote healthy aging. In recent years, the potential role of non-histone high-mobility group proteins (HMGs) in the regulation of aging and lifespan has attracted widespread attention. HMGs play critical roles in cellular senescence and associated diseases through various pathways, encompassing multi-layered mechanisms involving protein interactions, molecular regulation, and chromatin dynamics. This review provides a comprehensive analysis of the interactions between HMG family proteins and senescence-associated secretory phenotype (SASP), chromatin structure, and histone modifications, offering a deeper exploration of the pivotal functions and impacts of HMGs in the aging process. Furthermore, we summarize recent findings on the contributions of HMG proteins to aging and age-related diseases. HMG proteins not only regulate senescence-associated inflammation through modulating the SASP but also influence genomic stability and cell fate decisions via interactions with chromatin and histones. Targeting HMG proteins holds great potential in delaying the progression of aging and its associated diseases. This review aims to provide a systematic overview of HMG proteins' roles in aging and to lay a solid foundation for future anti-aging drug development and therapeutic strategies. With the advancing understanding of the mechanisms by which HMGs regulate aging, developing therapeutic interventions targeting HMGs may emerge as a promising approach to extending lifespan and enhancing healthspan.

Attributing human mortality from fire PM2.5 to climate change

Attributing human mortality from fire PM2.5 to climate change