Death Research Articles

SID/SIEDP expert consensus on optimizing clinical strategies for early detection and management of wolfram syndrome

Abstract Wolfram Syndrome (WFS) is a rare, multisystemic, degenerative disease leading to premature death. Clinical and genetic heterogeneity makes WFS diagnosis and management challenging. The Italian Society of Diabetes (SID) and the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP) convened an expert panel of professional healthcare practitioners to provide up-to-date knowledge about the pathophysiology, clinical presentation and treatment of WFS, and recommendations for the earlydetection and optimal disease management. The consensus recommends the revision of diagnostic protocols to include genetic testing and comprehensive multidisciplinary evaluations to ensure accurate diagnosis of WFS, advocates for personalized management plans tailored to the unique needs of each patient, with an emphasis on exploring new potential drug therapies. A holistic care model that addresses the medical, psychological, and social challenges faced by patients with WFS and their families is strongly endorsed. The opinion underscores the importance of educating healthcare professionals about WFS to enhance early diagnosis and intervention, aiming to improve outcomes for patients through practical and evidence-based clinical strategies.

Compound dry-hot-fire events connecting Central and Southeastern South America: an unapparent and deadly ripple effect

South America has experienced severe compound drought-heatwaves (CDHW), exacerbating fires. Recently, the unprecedented Pantanal 2020 fire season (P20F), burning a third of the biome, resulted in well-reported local impacts on the ecosystem, economy, and health. Nevertheless, the long-range ripple effects of this event remain unknown. We investigated the P20F-related cascading hazards, integrating models, observational and satellite-based data. P20F-related smoke elevated PM2.5 levels in the SA’s most populated area, exceeding WHO guidelines by up to 600%. Smoke-induced air pollution episodes coincided with widespread heatwaves, amplifying health risks. The mortality burden attributable to this multi-hazard short-term (14 days) exposure was estimated to be 2150 premature deaths (21% increase above expected levels). Our findings highlight that the impacts of CDHW-fires in SA are beyond the local level, implying growing challenges for risk management and public health and the need for governance based on telecoupled flows, linking different systems over multiple scales.

Life years lost by childhood cancer treatment and health related late effects among childhood cancer survivors

BackgroundIdentifying risk factors contributing the most to mortality of childhood cancer survivors is essential to guide harm reduction efforts in childhood cancer treatments, and long-term follow-up of childhood cancer survivors. MethodsWe assessed Life Years Lost from childhood cancer treatments and their health-related late effects among the French Childhood Cancer Survivors Study, a cohort of 7670 5-year childhood cancer survivors. Using a landmark strategy, we also assessed time-varying effects of risk factors, and how the multi-morbidity affects life years lost. ResultsWe found subsequent malignant neoplasm (9.0 years [95 %CI: 4.3–13.7]), severe cardiac disease (8.0 years [95 %CI: 1.2–14.9]), and the use of radiotherapy (6.0 years [95 %CI: 4.7–7.3]) to be the highest contributors to Life Years Lost among childhood cancer survivors. We found no interaction impact on life years lost between health related late effects considered. ConclusionsThose findings suggest that radiotherapy is the root cause of early mortality among childhood cancer survivors. Moreover patients experiencing a subsequent malignant neoplasm or a cardiac disease should be monitored closely after the event, as comorbidity is common and causes premature deaths.

Acute kidney injury predicts the risk of adverse cardio renal events and all cause death in southeast Asian people with type 2 diabetes

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Community beliefs and practices about diabetes and their implications for the prevention and management of diabetes in Southeast Ghana

BackgroundDiabetes is a major public health issue, and over half a billion people are estimated to be living with diabetes, with 6.7 million deaths reported in 2021. The global diabetes burden has been recognised and included in the United Nations Sustainable Development Goals to achieve a zero increase in diabetes cases and reduce one-third of premature diabetes deaths by 2030. However, local beliefs about the causes of diabetes have affected its prevention and management. This study examined community beliefs and practices about diabetes and how they affect the prevention and management of diabetes in the community.MethodsThis study was carried out in the Ho Municipality of the Volta Region of Ghana. We conducted 33 in-depth interviews with 18 patients with diabetes, 5 carers (caretakers of patients with diabetes), 3 traditional healers, 2 religious leaders, 3 community elders, and 2 assembly members who were purposefully selected from urban and rural areas across the municipality. The interviews were recorded digitally and transcribed verbatim. Thematic analysis was applied to analyse the data using QRS NVivo 20.ResultsDiabetes was described locally as sukli dɔ (sugar disease), which affects humans. Diabetes is believed to be caused by spiritual forces (juju, bewitchment, and punishment from gods) and physical factors (unhealthy diet, physical inactivity, eating fruits and vegetables sprayed with pesticides and insecticides, sugary and starchy foods, smoking, and abuse of alcohol). In terms of the management of diabetes, participants said traditional remedies are performed for spiritual interpretation, deliverance, fortification, and cleansing before biomedical and physical remedies are sought. Diabetes was likened to HIV/AIDS, and the sufferers were described as bringing the condition upon themselves as a result of their bad deeds. They were stigmatised, coupled with delays at the hospital, and poverty has also affected the prevention and management of diabetes.ConclusionThe local belief that diabetes is caused by spiritual forces, likened to HIV/AIDS, delays at hospitals, and poverty, has affected the prevention and management of diabetes. Incorporating local beliefs and practices into the intervention design using culturally sensitive health education programmes and improving social determinants of health may help improve the prevention and management of diabetes in communities.

Expert Opinion on the Role of Sacubitril/Valsartan in the Management of Hypertension in India.

Hypertension, a key modifiable risk factor for cardiovascular diseases (CVD), significantly contributes to premature death and morbidity worldwide. Despite stabilization in age-adjusted global prevalence, the absolute number of hypertensive individuals doubled from 2000 to 2010, largely due to increases in low- and middle-income countries. In 2021, only 21% of hypertensive individuals globally had effective blood pressure (BP) control. In India, hypertension is the leading risk factor for death and disability, with prevalence rates of 24% in men and 21% in women, as reported by the 2019-2020 National Family Health Survey (NFHS-5). Alarmingly, just 25% of rural and 38% of urban hypertensive Indians are undergoing treatment, with only 10% and 20% achieving BP control, respectively. This highlights the hypertension paradox, where clinical inertia and hesitancy in intensifying BP-lowering therapy persist despite the availability of antihypertensive drugs. This expert opinion paper aims to provide a comprehensive evaluation of sacubitril/valsartan in hypertension management, leveraging insights from its approved use in heart failure and examining its benefits and challenges across diverse hypertensive populations. The formulation of this expert opinion involved employing evidence-based methodologies and utilizing all available data. The document underwent scrutiny by expert cardiologists, whose clinical experiences and examination of the evidence and guidelines informed the formation of the expert opinion. This expert opinion paper provides a thorough and informed evaluation of sacubitril/valsartan, highlighting its potential to address unmet needs in BP control, particularly in challenging cases such as resistant hypertension and chronic kidney disease.

Burden of disease and cost of illness of overweight and obesity in Portugal.

The prevalence of overweight and obesity has increased in the last decades, posing significant health and economic impacts globally. These conditions are related to several non-communicable diseases, including cardiovascular disease, type II diabetes and cancer. This study estimated the disease burden and healthcare costs associated with overweight and obesity in the adult population in mainland Portugal, in 2018. Burden of disease was measured in disability-adjusted life years (DALY) following Global Burden of Disease (GBD) methodology. DALY were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). The analyses included morbidity, mortality and related costs directly related to overweight and obesity, as well as the attributable morbidity, mortality and related costs of of 25 selected diseases related to obesity (DrO). A prevalence-based cost analysis was conducted a from the perspective of the public National Health Service, including costs related to inpatient, outpatient care and pharmacological treatment. In 2018, total DALY amounted to 260,943, with 75% due to premature death (196,438 YLL) and 25% due to disability (64,505 YLD). The economic burden of overweight and obesity was estimated at approximately € 1,148 million. Of these, approximately € 13.3 million (1%) were costs related to the treatment of obesity, and the remaining were costs of DrO attributed to overweight and obesity. Outpatient care corresponded to 43% of total costs, pharmacological treatment 38%, and inpatient care 19%. Cardiovascular and cerebrovascular diseases were the largest contributor to total costs (38%), followed by type II diabetes (34%). Overweight and obesity incur a large disease and economic burden to the public healthcare sector, representing approximately 0.6% of the country´s gross domestic product and 5.8% of public health expenditures.

Influence of therapy exposures on specific late morbidities, prescription drug purchases, and mortality in aging male survivors of childhood cancer: A registry-based study.

Childhood cancer treatments predispose to late health problems and premature death. Our aim was to use national registry data to study associations between cancer therapy exposures and late health outcomes in aging male childhood cancer survivors (CCS). The study comprised 200 male CCS (survival ≥5 years) treated with conventional cancer therapy at a single institution in 1964-2000 and 1000 matched population controls. Analyses involved registry-based data on prescription drug purchases, reimbursements for chronic conditions, hospital admissions, and deaths that occurred ≥5 years after the cancer diagnosis. Mean age of CCS was 45.4 years. Compared to population controls, CCS had a higher risk for hospital admissions due to cardiovascular diseases and late mortality, both of which increased after age 40 years. CCS also had a higher risk for purchases of antihypertensives and lipid-lowering drugs within the last year of the study. Heart radiation ≥10 Gy was associated with hospitalizations due to cardiovascular diseases (HR 4.14, 95%CI 1.81-9.48), purchases of antihypertensives (OR 3.05, 95%CI 1.32-7.36), and purchases of lipid-lowering drugs (OR 2.93, 95%CI 1.08-7.73). Testosterone deficiency developed typically during pediatric follow-up, and it was associated with testicular radiation ≥20 Gy (HR 41.2, 95%CI 15.4-110) but not with alkylating agents. Of patients treated with testicular radiation ≥20 Gy, 91% had purchased testosterone within the last year. Reassuringly, CCS had no excess risk for purchases of opioids, anxiolytics, antiepileptics, or antidepressants. These findings emphasize the need for risk-based follow-up. Middle-aged male CCS are at an increased risk of premature cardiovascular morbidity and excess mortality.

Frailty transition and burden on mortality risk in middle-aged and older population: a prospective cohort study

The effect of frailty transition and burden on the risk of all-cause mortality in South Korea remains unclear. This study aimed to investigate the risk of all-cause mortality using the most recent frailty index (FI), changes in FI, and frailty burden. We analyzed data from the Korean Genome and Epidemiology Study (2013–2020). A total of 3,134 participants aged 53–87 years with a computable FI based on the osteoporotic fracture index during their initial visit. The FI was updated biennially during re-examinations and changes between the initial and last visits were categorized into four groups: (1) improved or maintained to non-frail, (2) worsened to pre-frail, (3) improved or maintained to pre-frail, and (4) worsened or maintained to frail. We used the Cox proportional hazards model, adjusted for age, sex, education, lifestyle factors, and diseases. During the follow-up, 218 participants died. Compared to those who were robust at the last visit, pre-frailty and frailty were associated with an increased risk of all-cause death. Of those who visited > 2 times, 62.3% improved or remained robust, and had a decreased risk of all-cause death. Those with > 63% of pre-frailty or frailty burden significantly higher risk of death, with > 60% increase compared to their non-frail counterparts. Maintaining or achieving robustness is associated with a decreased risk of mortality. To prevent premature death and extend healthy life expectancy, identifying biological aging through surrogate measures and implementing interventions to maintain or achieve a robust health status are needed.

Burden of Ischemic Heart Diseases among US States from 1990-2019.

Ischemic Heart Disease (IHD) is a leading cause of global mortality, including in the United States. Understanding the burden of IHD in the United States is crucial for informed decision-making and targeted interventions aimed at reducing morbidity and mortality associated with this leading cause of death. This study aimed to understand the burden of IHD, identify gender disparities and risk factors, explore the relationship between socioeconomic growth and IHD, and analyze risk factor distribution across the states of the United States. This study utilized data from the Global Burden of Diseases Study 2019, which provided comprehensive information on IHD from 1990 to 2019. Data related to IHD from these years were extracted using a query tool from the Institute for Health Metrics and Evaluation (IHME) website. The study assessed the relationship between IHD and socioeconomic development using the Socio-demographic Index (SDI) and measured the overall impact of IHD using Disability-adjusted Life Years (DALYs), considering premature death and disability. Additionally, the study analyzed the burden of IHD attributed to six main risk factors. Data analysis involved comparing prevalence, mortality, SDI, DALYs, attributable burden, and risk estimation among the states. Between 1990 and 2019, there was an improvement in socioeconomic development in all states. Age-standardized rates of disease burden for IHD decreased by 50% [ASDR 3278.3 to 1629.4 (95% UI: 1539.9-1712.3) per 100,000] with the most significant decline observed in Minnesota. Males had higher burden rates than females in all states, and the southeast region had the highest mortality rates. The prevalence of IHD showed a declining trend, with approximately 8.9 million cases (95% UI: 8.0 million to 9.8 million) in 2019, representing a 37.1% decrease in the Age-standardized Prevalence Rate (ASPR) from 1990. Metabolic risks were the leading contributors to the disease burden, accounting for 50% of cases, with Mississippi having the highest attributable risk. Arkansas had the highest attributable risk for high cholesterol and smoking. Conversely, Minnesota had the lowest burden of IHD among all the states. This study highlights variations in the burden of IHD across US states and emphasizes the need for tailored prevention programs to address specific risk factors and gender differences. Understanding the trend in IHD may inform policymakers and healthcare professionals in effectively allocating resources to reduce the burden of IHD and improve national health outcomes.

Regional and ethnic factors of obesity and diabetes mellitus in women of re-productive age in the Pribaikal region

Introduction. Overweight is currently one of the leading global medical problems. Overweight and obesity contribute significantly to the development of diseases such as diabetes, cardiovascular disorder and can also cause premature death. Obesity has a negative impact on reproductive function; almost a quarter of women of childbearing age are overweight and about a third of them are obese.Aim. To study the characteristics of carbohydrate metabolism, hormonal indicators, and clinical-metabolic profiles, as well as to assess the potential risk of developing diabetes mellitus in women of fertile age with overweight and obesity residing in the Baikal region.Materials and methods. The study involved 60 overweight and obese women of reproductive age in the Pribaikalye region, including 33 women of Russian nationality (group 1) and 27 women of Buryat nationality (group 2). Anthropo-metric, sociodemographic and behavioural criteria were analysed, as well as questionnaires using the FINDRISC Scale. General clinical analyses of blood and urine were performed, lipid profile parameters, glucose, insulin, creatinine, transaminases, estradiol, thyroid hormone, leptin levels in blood plasma were studied. In addition, an oral glucose tolerance test was performed and the insulin resistance index (HOMA-IR) was calculated.Results. In the group of Buryat women with lower body weight as compared to Russians, higher levels of leptin, HOMA- IR index, and larger waist circumference are observed. In Buryat women, low physical activity makes a significant contribution to the development of overweight and obesity, while for Russian women, excessive caloric intake is more important. In accordance with the results of the FINDRISC scale survey, the greatest contribution to the potential development of diabetes mellitus in the Russian group is body mass index (weight), and in the Buryat group, in addition to these indicators, waist circumference and reduced physical activity.Conclusions. The results of the study will be of great help in the development of pro-grammes for the prevention of diabetes and obesity, taking into account regional and ethnic differences among the population.

Single-agent Adavosertib Shows Anticancer Effects Against Colorectal Cancer Cells.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related deaths worldwide. Adavosertib (AZD1775), a small molecule inhibitor of WEE1 kinase, abrogates G2/M cell cycle arrest and induces double-stranded DNA breaks. According to previous findings, adavosertib, in combination with other DNA-damaging agents, causes premature mitosis and cell death in p53-mutated cancer cells mainly via abrogation of the G2/M cell cycle checkpoint. This study aims to evaluate the inhibition of WEE1 kinase by adavosertib as monotherapy in the TP53-wildtype human CRC cell line HCT116. In this study, HCT116 cells were treated with different concentrations of adavosertib for 24 to 72 hours. Cell viability was assessed by Water-Soluble Tetrazolium 1 (WST-1) assay and crystal violet assays. Cell migration was evaluated by the wound healing assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The IC50 value of adavosertib for the HCT116 cell line was 0.1310 μM. Adavosertib monotherapy (both 0.125 and 0.250 μM) significantly reduced cell viability, inhibited cell migration and abrogated intra-S phase cell cycle arrest. In addition, 0.250 μM of adavosertib significantly induced apoptosis in HCT116 cells. Adavosertib effectively inhibits the TP53-wildtype HCT116 cells via the abrogation of intra-S phase cell cycle arrest. Our findings suggest that adavosertib monotherapy may be a potential targeted therapy for CRC.

Alcohol and mortality in Mexico: prospective study of 150 000 adults

Alcohol consumption is a leading cause of premature death globally, but there is no large-scale prospective evidence from Mexico. The Mexico City Prospective Study recruited 150 000 adults aged 35 years or older between 1998 and 2004. Participants were followed up until Oct 1, 2022 for cause-specific mortality. Cox regression in those with no self-reported chronic disease at entry (adjusted for age, sex, district, education, physical activity, smoking, and diabetes) was used to relate baseline-reported alcohol consumption (never, former, occasional [less than monthly], and regular [at least monthly, split into <70, ≥70 to <140, ≥140 to <210, and ≥210 g/week]) to mortality at ages 35-74 from all causes, and from a pre-specified alcohol-related set of underlying causes. Heavy episodic drinking (normally consuming >5 [men] or >4 [women] drinks on a single occasion) and type of preferred drink were also examined. Among 138 413 participants aged 35-74 years at recruitment, 21 136 (15%) were regular alcohol drinkers (14 863 [33%] men, 6273 [7%] women), of whom 13 383 (63%) favoured spirits and 6580 (31%) favoured beer. During follow-up, there were 13 889 deaths at ages 35-74 years, including 3067 deaths from the pre-specified alcohol-related causes. Overall, J-shaped associations with mortality were observed. Compared with occasional drinkers, those with baseline-reported consumption ≥210 g/week had 43% higher all-cause mortality (rate ratio [RR] 1·43 [95% CI 1·30-1·56]) and nearly three times the mortality from the pre-specified alcohol-related causes (2·77 [2·39-3·20]). Death from liver disease was strongly related to alcohol consumption; the RR comparing regular drinkers of ≥140 g/week with occasional drinkers was 4·03 (3·36-4·83). Compared with occasional light drinking, occasional heavy episodic drinking was associated with 20% higher alcohol-related mortality (1·20 [1·06-1·35]), and regular heavy episodic drinking was associated with 89% higher alcohol-related mortality (1·89 [1·67-2·15]). Drinks with alcohol percentages higher than spirits were associated with the greatest increased mortality risk, even after accounting for the total alcohol consumed. In this Mexican population, higher alcohol consumption, episodic drinking, and very high percentage alcoholic products were all associated with increased mortality. Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council. For the Spanish translation of the abstract see Supplementary Materials section.

Quantification and spatial analysis of gridded (0.1° × 0.1°) emission of indirect GHGs/Air pollutants from anthropogenic sources in India

Indirect greenhouse gases (GHGs) play a key role in modulating both regional and global atmospheric chemistry and act as air pollutants that degrade air quality. The rising number of premature deaths and notable health hazards could be linked to increasing concentration of these air pollutants in the atmosphere. As a developing nation, India is often regarded as one of the most polluting countries due to increasing anthropogenic activities. Therefore, identifying the sources of these indirect GHGs gases such as CO, NOx, VOC and SO2 and quantifying their emissions has become a critical requirement for understanding regional atmospheric chemistry. In this study, we developed a comprehensive, technology-driven gridded emission inventory for India at a high resolution (0.1°×0.1°) for the base year 2020. Using the IPCC bottom-up approach, the study estimated the total emissions of CO (45 Tg/yr), NOx (22.8 Tg/yr), VOC (10.8 Tg/yr) and SO2 (15.1 Tg/yr) from all the dominating sources. Vehicle exhaust contributes the most NOx and VOC whereas the residential and power sectors are the highest emitters of CO and SO2, respectively. This newly reported surface emission data would be an essential tool for policymakers in formulating mitigation strategies and will also serve as a vital input for atmospheric chemistry and climate studies.

Biased allosteric modulator of neurotensin receptor 1 reduces ethanol drinking and responses to ethanol administration in rodents

Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7th leading cause of premature death [1]. Despite this, there are currently only 3 FDA approved pharmacological approaches for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse. Recently, a novel compound, SBI-553, that biases the action of Nts receptor 1 (NTSR1) activation, has shown promise in preclinical models of psychostimulant use. Here we investigate the efficacy of this compound to alter ethanol-mediated behaviors in a comprehensive battery of experiments assessing ethanol consumption, behavioral responses to ethanol, physiological sensitivity to ethanol, and ethanol metabolism. Additionally, we investigated behavior in avoidance and cognitive assays to monitor potential side effects of SBI-553. We find that SBI-553 reduces ethanol consumption in mice without altering avoidance behavior or novel object recognition. We also observe sex-dependent differences in physiological responses to sequential ethanol injections in mice. In rats, we show that SBI-553 attenuates sensitivity to the interoceptive effects of ethanol (using a Pavlovian drug discrimination task). Our data suggest that targeting NTSR1 signaling may be promising to attenuate alcohol misuse, and adds to a body of literature that suggests NTSR1 may be a common downstream target involved in the psychoactive effects of multiple reinforcing substances.

Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS. To tackle this question, we generated atherosclerosis-free mice (LmnaLCS/LCSCdh5-CreERT2) and atheroprone mice (Apoe-/-LmnaLCS/LCSCdh5-CreERT2) with EC-specific progerin expression. Like progerin-free controls, LmnaLCS/LCSCdh5-CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone Apoe-/-LmnaLCS/LCSCdh5-CreERT2 mice showed no alteration in body weight or lifespan versus Apoe-/-LmnaLCS/LCS controls and did not develop vascular alterations or aggravated atherosclerosis. Our results indicate that progerin expression in ECs is not sufficient to cause the cardiovascular phenotype and premature death associated with progeria.

The health impact of PM2.5 and O3 in Beijing modified by infiltration factors from 2014 to 2022.

PM2.5 and O3 are significant threats to the health of residents and modern residents spend more than 80% of their time indoors, so quantifying indoor exposure of residents has a positive influence on formulating policies and improving health indicators. Analysis of monitoring data shows a consistent decrease in the annual average concentration of outdoor PM2.5 in Beijing from 90.1 to 30.4μg/m3, and the equivalent human exposure concentration also declined from 55.2 to 18.6μg/m3 modified by infiltration factors from 2014 to 2022, while during the peak season, the average value of O3-8h concentration in Beijing has consistently remained between 159.3 and 225.3μg/m3; the equivalent human exposure concentration remained between 64.7 and 92.3μg/m3 modified by infiltration factors from 2014 to 2023. The equivalent exposure concentration is calculated by weighting the concentration of indoor and outdoor pollutants, the proportion of indoor and outdoor activity time of the population, and the permeability coefficient of outdoor pollutants into the room, so as to quantify the actual concentration of pollutants exposed to the human body in a certain time. Previous studies have primarily focused on the impact of annual changes in pollutant concentrations on health estimates, often neglecting indoor concentrations and behavior patterns. This limitation should be addressed. Therefore, this study utilized equivalent human exposure concentration and AirQ + , the authoritative software released by the World Health Organization (WHO), to evaluate quantitatively the impact of PM2.5 and O3 on the health of Beijing residents by combining pollutant concentration, annual population, and mortality of various diseases and other indicators to enhance the credibility of the study. The number of deaths related to PM2.5 has decreased from 28,182 people in 2014 to 10,250 people in 2022 (age ≥ 30). The number of premature deaths in 2022 was only 36.4 percent of that in 2014 and was decreasing by 1992 per year. The number of deaths related to O3 varies between 550 and 3358 people. Lowering PM2.5 and O3 concentrations can effectively reduce natural premature death as well as cardiovascular and respiratory diseases caused by air pollution. The government should persist in enhancing the regulation of PM2.5 and accord significance to the oversight of O3. Concurrently, there is a need to reinforce the cooperative regulation addressing both PM2.5 and O3.

Merleau-Ponty nos arquivos Husserl: uma entrevista com Emmanuel de Saint Aubert

Silvana de Souza Ramos and Iracy Ferreira dos Santos Junior’s interview with Emmanuel de Saint Aubert explores the history and role of the Husserl Archives (Paris) in fostering multidisciplinary research in phenomenology. Saint Aubert clarifies Merleau-Ponty’s engagement with Husserl’s manuscripts, describing the situated and complex reading he undertook not only of these manuscripts but also of Husserl’s work as a whole. This aspect is particularly significant for contemporary French philosophical studies, as Merleau-Ponty played a pivotal role in introducing Husserl’s ideas into French thought. This clarification allows us to show the originality of Merleau-Ponty’s philosophy, as it reveals that he was not merely an exegete of Husserl, but a restless and multifaceted thinker, deeply involved in the intellectual and political debates of his time. If he cannot be reduced to a mere reader of Husserl, neither can his later ontology be simply attributed to Heidegger’s influence. Once engaged in a meticulous study of the unfinished manuscripts that Merleau-Ponty left behind due to his premature death, which were drafts for a new book, Saint Aubert conducted a thorough investigation of Merleau-Ponty’s use of key terms in his ontology – chair, Leib, empiétement, chiasmi – showing that these terms do not literally translate or express concepts derived from Husserl or Heidegger. On the contrary, these terms acquire a multifaceted range of meanings in Merleau-Ponty’s writings, nourished by his philosophical readings and meditations, by his scientific and literary refinement, as well as his ethical and political concerns. Saint Aubert’s research, dedicated to the interpretation of Merleau-Ponty’s so-called “unpublished” works, resulted in the publication of five books by Vrin, all guided by a transversal genetic reading of Merleau-Ponty’s work. Additionally, with the help of other researchers, Saint Aubert carefully edited and published several volumes of Merleau-Ponty’s manuscripts. This material, made available in an organized and contextualized manner, is of incomparable richness, allowing for a more precise understanding of Merleau-Ponty’s role in contemporary thought, while also illuminating the meaning of his ontological project.

“THE SERMON ON THE DEC EASED” BY HRYHORII TSAMBLAK: RECENSIONS, POETICS, AND STYLE

The copy of “The Sermon on the Deceased” by Hryhorii Tsamblak, preserved in the library of the Kyiv Cave Monastery, was written in the 16th or early 17th century at the Belarusian Suprasl Monastery. This sermon is a part of the so-called “Hryhorii Tsamblak’s Book,” which may have been compiled by the author himself during his tenure as Kyivan metropolitan. The examined copy of the “The Sermon on the Deceased” and the copy of the same work kept in the scientific library of the Lithuanian Academy of Sciences in Vilnius are of Belarusian origin and differ significantly from the copies created in the Moscow principality. Therefore, it can be assumed that the Kyiv and Vilnius codices originate from a common protograph that was modified either by the author himself or by a scribe in the territory of the Grand Duchy of Lithuania. In “The Sermon on the Deceased,” Hryhorii Tsamblak shares his thoughts on the Christian custom of commemorating the dead. The preacher optimistically proclaims an eschatological perspective for Christians. The didactic purpose of Tsamblak’s sermon is to illuminate the futility of earthly concerns and efforts. The ontological perspective for the righteous pertains to the hope of the resurrection of the dead and eternal life. Based on numerous examples of human activity, such as the hard lives of warriors, farmers, sailors, and ore miners, the preacher attempts to illustrate the concept of “the vanity of vanities” and “the hurricane of human life that passes quickly.” Tsamlak argues that the Christian’s axiology should oppose the cult of enrichment, power, and vanity. Metaphorically and symbolically, he portrays the work of a farmer hoping for a good harvest, which represents the imperishable — eternal life in Christ. “The Sermon on the Deceased” was influenced by the sermons of John Chrysostom and, probably, by one of the works of Macarius the Great. The style of Tsamblak’s sermon can be defined as emotionally expressive.

Blood pressure management protocol based on transtheoretical model effectiveness on self- care: A systematic review

Background: Hypertension is a prevalent medical condition associated with cardiovascular and kidney diseases, leading to premature death and disability. Despite medication use, hypertension continues to rise due to unhealthy lifestyles. Self-care strategies play crucial roles in effectively treating hypertension. We aimed to evaluate the effectiveness of interventions based on the transtheoretical model (TTM) in improving self-care, self-efficacy, and health-related quality of life (HRQOL) in hypertensive adults. Methods: A comprehensive search was performed in multiple databases using appropriate search strategies. Two independent reviewers screened articles, and assessed their adherence to the inclusion and exclusion criteria. The risk of bias in randomized controlled trials was assessed by the Cochrane Collaboration tool and quasi-experimental studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Quasi-Experimental Studies. Results: The review included 24 studies with a total of 6553 participants. Most interventions aimed to encourage a healthier lifestyle and improve diet and physical activity. The message was delivered through various methods such as slide/tape messages, individual education/counseling sessions, telephone-delivered interventions, and multimedia training software based on the TTM. Control groups received physician visits or attended lifestyle lectures but did not receive specific behavior change programs like the intervention groups. Conclusion: Our results indicated that the TTM and stage of change model can be an appropriate framework for delivering educational messages to patients.