BI-3231, an enzymatic inhibitor of HSD17B13, reduces lipotoxic effects induced by palmitic acid in murine and human hepatocytes.

17-ß-hydroxysteroid dehydrogenase 13 (HSD17B13), a lipid droplet-associated enzyme, is primarily expressed in the liver and plays an important role in lipid metabolism. Targeted inhibition of enzymatic function is a potential therapeutic strategy for treating steatotic liver disease (SLD). The present study is aimed at investigating the effects of the first selective HSD17B13 inhibitor, BI-3231, in a model of hepatocellular lipotoxicity using human cell lines and primary mouse hepatocytes in vitro. Lipotoxicity was induced with palmitic acid in HepG2 cells and freshly isolated mouse hepatocytes and the cells were coincubated with BI-3231 to assess the protective effects. Under lipotoxic stress, triglyceride (TG) accumulation was significantly decreased in the BI-3231-treated cells compared with that of the control untreated human and mouse hepatocytes. In addition, treatment with BI-3231 led to considerable improvement in hepatocyte proliferation, cell differentiation, and lipid homeostasis. Mechanistically, BI-3231 increased the mitochondrial respiratory function without affecting ß-oxidation. BI-3231 inhibited the lipotoxic effects of palmitic acid in hepatocytes, highlighting the potential of targeting HSD17B13 as a specific therapeutic approach in steatotic liver disease.NEW & NOTEWORTHY 17-ß-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a lipid droplet protein primarily expressed in the liver hepatocytes. HSD17B13 is associated with the clinical outcome of chronic liver diseases and is therefore a target for the development of drugs. Here, we demonstrate the promising therapeutic effect of BI-3231 as a potent inhibitor of HSD17B13 based on its ability to inhibit triglyceride accumulation in lipid droplets (LDs), restore lipid metabolism and homeostasis, and increase mitochondrial activity in vitro.

Janus kinase 2 inhibition by pacritinib as potential therapeutic target for liver fibrosis.

BACKGROUND AND AIMS: Janus kinase 2 (JAK2) signaling is increased in human and experimental liver fibrosis with portal hypertension. JAK2 inhibitors, such as pacritinib, are already in advanced clinical development for other indications and might also be effective in liver fibrosis. Here, we investigated the antifibrotic role of the JAK2 inhibitor pacritinib on activated hepatic stellate cells (HSCs) in vitro and in two animal models of liver fibrosis in vivo . APPROACH AND RESULTS: Transcriptome analyses of JAK2 in human livers and other targets of pacritinib have been shown to correlate with profibrotic factors. Although transcription of JAK2 correlated significantly with type I collagen expression and other profibrotic genes, no correlation was observed for interleukin-1 receptor-associated kinase and colony-stimulating factor 1 receptor. Pacritinib decreased gene expression of fibrosis markers in mouse primary and human-derived HSCs in vitro . Moreover, pacritinib decreased the proliferation, contraction, and migration of HSCs. C 57 BL/6J mice received ethanol in drinking water (16%) or Western diet in combination with carbon tetrachloride intoxication for 7 weeks to induce alcoholic or nonalcoholic fatty liver disease. Pacritinib significantly reduced liver fibrosis assessed by gene expression and Sirius red staining, as well as HSC activation assessed by alpha-smooth muscle actin immunostaining in fibrotic mice. Furthermore, pacritinib decreased the gene expression of hepatic steatosis markers in experimental alcoholic liver disease. Additionally, pacritinib protected against liver injury as assessed by aminotransferase levels. CONCLUSIONS: This study demonstrates that the JAK2 inhibitor pacritinib may be promising for the treatment of alcoholic and nonalcoholic liver fibrosis and may be therefore relevant for human pathology.

Alcohol consumption patterns and adherence to the Mediterranean diet in the adult population of Spain.

PURPOSE: The objective is to evaluate the association between various indicators of alcohol consumption and the degree of adherence to the Mediterranean diet among the Spanish adult population. METHODS: A cross-sectional study including 44,834 participants ≥ 15 years of age from the 2017 National Health Survey and the 2020 European Health Survey in Spain. Alcohol patterns were defined based on (1) average intake: individuals were classified as low risk (1-20 g/day in men and 1-10 g/day in women) and high risk (> 20 g/day in men or > 10 g/day in women), (2) binge drinking, and (3) alcoholic beverage preference. Non-adherence to the Mediterranean diet was defined as scoring < 7 points on an adapted Mediterranean Diet Adherence Screener index (range 0-10). Odds ratios (OR) were estimated using logistic regression models adjusted for relevant covariates. RESULTS: Compared to non-drinkers, low and high-risk drinkers were more likely to report non-adherence to the Mediterranean diet: ORs 1.35 (95% CI 1.23; 1.49) and 1.54 (95% CI 1.34; 1.76), respectively. Similarly, reports of binge drinking less than once a month was associated with higher likelihood of non-adherence (OR 1.17; 95% CI 1.04; 1.31). Individuals reporting no preference for a specific beverage and those with a preference for beer or for spirits had lower adherence: ORs 1.18 (95% CI 1.05; 1.33), 1.31 (95% CI 1.17; 1.46), and 1.72 (95% CI 1.17; 2.54), respectively, while a preference for wine showed no association (OR 1.01; 95% CI 0.90; 1.13). CONCLUSION: Alcohol consumption, even in low amounts, is associated with lower adherence to the Mediterranean diet. Therefore, alcoholic beverages should not be included in measures that define the Mediterranean diet.

Dynamic human liver proteome atlas reveals functional insights into disease pathways.

Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell type resolution to predict outcome and design therapy. Here, we quantify more than 150,000 sequence-unique peptides aggregated into 10,000 proteins across total liver, the major liver cell types, time course of primary cell cultures, and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serve as spectral library to characterize a human cohort of non-alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver tissue include signatures of hepatic stellate cell activation resembling liver cirrhosis and providing functional insights. We built a web-based dashboard application for the interactive exploration of our resource (www.liverproteome.org).

Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice.

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses.

Clustering of unhealthy lifestyle behaviors, self-rated health and disability.

The main objective was to identify sociodemographic characteristics of the population at risk for a greater clustering of unhealthy behaviors and to evaluate the association of such clustering with self-rated health status and disability. Data come from the 2017 Spanish National Health Survey with a sample of 21,947 participants of 15 years of age or older. Based on tobacco consumption, risk drinking, unbalanced diet, sedentarism, and body mass index <18.5/≥25 we created two indicators of risk factor clustering: 1) Number of unhealthy behaviors (0-5); and 2) Unhealthy lifestyle index (score: 0-15). Self-rated health was dichotomized into "optimal" and "suboptimal," and disability was classified as "no disability," "mild," and "severe" based on the Global Activity Limitation Index (GALI). We estimated prevalence ratios (PR) adjusted for covariates using generalized linear models using the clustering count variable, and dose-response curves using the unhealthy lifestyle index. Most participants (77.4%) reported 2 or more risk factors, with men, middle-age individuals, and those with low socioeconomic status being more likely to do so. Compared to those with 0-1 risk factors, the PR for suboptimal health was 1.26 (95% CI:1.18-1.34) for those reporting 2-3 factors, reaching 1.43 (95% CI:1.31-1.55) for 4-5 factors. The PR for severe activity limitation was 1.66 (95% CI:1.35-2.03) for those reporting 2-3 factors and 2.06 (95% CI:1.59-2.67) for 4-5 factors. The prevalence of both health indicators increased in a non-linear fashion as the unhealthy lifestyle index score increased, increasing rapidly up to 5 points, slowing down between 5 and 10 points, and plateauing afterwards.

Mentoring Experiences of Male Faculty in Nursing Programs.

AIM: The aim of this study was to examine the mentoring experiences of male faculty in nursing programs. BACKGROUND: Recruiting and retaining male nursing faculty is important to achieve a workforce that reflects the diversity of society. Mentoring is one way to help recruit and retain male nursing faculty. METHOD: Ten male nursing faculty in academia comprised the sample for this qualitative, descriptive study. RESULTS: Reflection on the mentoring male nursing faculty received for career and psychosocial development revealed the following themes: early supporters, figuring it out, making connections, paying it forward, and the role of gender. Facilitators and barriers to mentoring experiences are described. CONCLUSION: Results of this study may be used to support investment in mentoring programs to recruit and retain male nursing faculty in academia and promote a diverse nursing workforce.

Combination of phosphodiesterase-5-inhibitors and beta blockers improves experimental portal hypertension and erectile dysfunction.

BACKGROUND & AIMS: Phosphodiesterase-5 inhibitors (PDE-5-I) are used for treatment of erectile dysfunction (ED), which is common in patients with cirrhosis. They may improve portal hypertension (PH), but contradictory data on efficacy and side-effects have been reported. Non-selective beta blockers (NSBB) reduce portal pressure, but might aggravate ED. Thus, we evaluated the combination of PDE-5-I with NSBB and its impact on PH and ED in experimental cirrhosis. METHODS: ED was assessed in cirrhotic patients (n = 86) using standardized questionnaire. Experimental cirrhosis was induced by bile-duct-ligation or carbon-tetrachloride intoxication in rats. Corpus cavernosum pressure - a surrogate of ED -, as well as systemic and portal haemodynamics, were measured in vivo and in situ after acute administration of udenafil alone or in combination with propranolol. mRNA and protein levels of PDE-5 signalling were analysed using PCR and western Blot. RESULTS: ED in humans was related to severity of liver disease and to NSBB treatment. PDE-5 was mainly expressed in hepatic stellate cells and upregulated in human and experimental cirrhosis. Propranolol reduced corpus cavernosum pressure in cirrhotic rats and it was restored by udenafil. Even though udenafil treatment improved PH, it led to a reduction of mean arterial pressure. The combination of udenafil and propranolol reduced portal pressure and hepatic resistance without systemic side-effects. CONCLUSIONS: ED is common with advanced cirrhosis and concomitant NSBB treatment. The combination of PDE-5-I and NSBB improves ED and PH in experimental cirrhosis.

Individual and Contextual Factors Associated With Hazardous Drinking in Spain: Evidence From a National Population-Based Study.

BACKGROUND: Heavy drinking (HD) and binge drinking (BD) exhibit marked differences in their relationships with contextual-level factors imbedded in geographical areas of residence. The objective is to identify sociodemographic factors, both at the individual and at the contextual level, associated with these 2 main hazardous consumption patterns. METHODS: Cross-sectional study using data from the 2011 to 2012 National Health Survey in Spain. The sample included 21,007 individuals ≥15 years of age. HD was defined as an alcohol intake of ≥40 g/d in men and ≥24 g/d in women. BD was defined as the consumption in the previous month of ≥6 alcoholic drinks (men) or ≥5 drinks (women) within 4 to 6 hours. Individual-level variables included sociodemographic factors, urban/rural residence, smoking, and perceived social support. Contextual-level variables covered percentage of population with no schooling, unemployment rate, and hospitality industry-related economic activity, all at the census tract level. We analyzed data using multilevel logistic regression and calculated areas under the curve (AUC). RESULTS: Being male, smoking, high-income, and low perceived social support were associated with both hazardous drinking patterns. Younger individuals were at higher risk for BD but at lower risk for HD. BD was more common among rural than urban dwellers (odds ratios [OR] = 1.35; 95% CI: 1.05 to 1.72), whereas HD was less likely in participants residing in areas with high unemployment rates (OR = 0.62; 95% CI: 0.41 to 0.93). HD was more likely in census tracts with higher levels of hospitality industry activity (OR = 1.74; 95% CI: 1.20 to 2.54). The AUC increased substantially for both HD and BD when the census tract variable was entered in the respective models (reaching 89.5 and 93.3%, respectively). CONCLUSIONS: Except for age, both drinking patterns have similar associations with individual-level variables but disparate links to contextual-level indicators. In both cases, accounting for area of residence substantially increased the ability to discriminate between high-risk drinkers from nonhazardous alcohol consumers.

Temperature-related excess mortality in German cities at 2 °C and higher degrees of global warming.

BACKGROUND: Investigating future changes in temperature-related mortality as a function of global mean temperature (GMT) rise allows for the evaluation of policy-relevant climate change targets. So far, only few studies have taken this approach, and, in particular, no such assessments exist for Germany, the most populated country of Europe. METHODS: We assess temperature-related mortality in 12 major German cities based on daily time-series of all-cause mortality and daily mean temperatures in the period 1993-2015, using distributed-lag non-linear models in a two-stage design. Resulting risk functions are applied to estimate excess mortality in terms of GMT rise relative to pre-industrial levels, assuming no change in demographics or population vulnerability. RESULTS: In the observational period, cold contributes stronger to temperature-related mortality than heat, with overall attributable fractions of 5.49% (95%CI: 3.82-7.19) and 0.81% (95%CI: 0.72-0.89), respectively. Future projections indicate that this pattern could be reversed under progressing global warming, with heat-related mortality starting to exceed cold-related mortality at 3 °C or higher GMT rise. Across cities, projected net increases in total temperature-related mortality were 0.45% (95%CI: -0.02-1.06) at 3 °C, 1.53% (95%CI: 0.96-2.06) at 4 °C, and 2.88% (95%CI: 1.60-4.10) at 5 °C, compared to today's warming level of 1 °C. By contrast, no significant difference was found between projected total temperature-related mortality at 2 °C versus 1 °C of GMT rise. CONCLUSIONS: Our results can inform current adaptation policies aimed at buffering the health risks from increased heat exposure under climate change. They also allow for the evaluation of global mitigation efforts in terms of local health benefits in some of Germany's most populated cities.

Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats.

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-ß1 (TGF-ß1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1ß (IL1ß) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1ß and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin-angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.

Evaluation of physicochemical properties and bacterial photoinactivation of phenothiazine photosensitizers.

We report herein the physicochemical properties and antimicrobial activity of a new monobrominated derivative of Azure B and its parent compound. These dyes are used as photosensitizers for photodynamic therapy and photodynamic antimicrobial chemotherapy. Relevant pharmaceutical properties (pKa, chemical and photochemical stability, and in vitro antimicrobial activity) were determined. A UV-visible spectrophotometry method was developed and validated according to the International Conference on Harmonization (ICH) guidelines for use in stability indicating studies and determination of the acid dissociation constant of Azure B and its monobrominated derivative. The results showed that both dyes were chemically stable. In addition, bromination of the phenothiazine dye decreased its photochemical stability and pKa value without affecting the ionization rate at physiological pH. The analytical parameters for validation of the method were linearity (r2 > 0.9981), limit of detection (LOD) (0.2-0.9 µM), limit of quantification (LOQ) (0.6-2.7 µM), and intra-day precision (0.76-1.40%) expressed as relative standard deviation (RSD). Recoveries ranging from 99.5 to 100.9% were obtained for the two dyes. Thus, this method provides a simple, sensitive, accurate, and precise assay for the determination of all compounds. The effect of photosensitizer concentration and visible irradiation time on lethal photosensitization against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was investigated. Both photosensitizers were active against the evaluated bacteria. However, the new monobrominated derivative was more effective than its predecessor and managed to eradicate these microorganisms by using different doses of the dye and light. In other words, a lower concentration of AzBBr and irradiation time were required to cause bacterial death equal to or greater than its precursor. The photodynamic efficacy of the two photosensitizers presented the following order: S. aureus > E. coli > P. aeruginosa. These studies indicated that the tested dyes satisfy the conditions of potential photosensitizers in terms of physicochemical and antimicrobial properties.

Mechanistic Insight into the Photodynamic Effect Mediated by Neutral Red and a New Azine Compound in Staphylococcus aureus Cells.

The photodynamic activity of Neutral Red and the new monobrominated Neutral Red was studied in suspensions of Staphylococcus aureus. The effect of mannitol and sodium azide in the presence of 25 µm photosensitizer on lethal photosensitization were investigated. The results of the mechanistic evaluation of Neutral Red showed that both mannitol and sodium azide produced a completed protective effect after irradiation without significant differences between them. The evaluation of monobrominated Neutral Red also showed a protective effect of microorganisms with the addition of mannitol. Although sodium azide produced a protective effect of the photoinactivation, it was incomplete and less than that exhibited by mannitol. The results indicate that the starting reagent, Neutral Red, is a producer of radical species, acting through a type I mechanism, whereas the halogenated derivative of Neutral Red produced reactive oxygen species and a contribution of singlet molecular oxygen cannot be discarded in the photoinactivation of Staphylococcus aureus cells. These results, analyzed together with the previously evaluated properties of the dyes, allow us to explain the differences observed in the photoinactivation of Staphylococcus aureus mediated by both azine photosensitizers.

Actively Involving Middle School Students in the Implementation of a Pilot of a Behavioral Economics-Based Lunchroom Intervention in Rural Schools.

School-based interventions can play an important role in improving childhood and adolescent nutrition and preventing obesity. Schools offer a unique opportunity to implement policy, systems, and environmental interventions targeting healthy eating behaviors. An intervention was piloted in six middle schools featuring behavioral economics-based changes to the lunchroom, communication training, and communicate cues for food service staff. The pilot study employed a multicomponent evaluation with students and food service directors and staff including a lunchroom assessment, online surveys, production records, and interviews. Five schools increased their scores on the lunchroom assessment tool, and four schools increased the number of servings produced of healthy food items. Interviews with food service directors indicated the interventions was feasible and well received. School-based policy, systems, and environmental interventions targeting healthy eating behaviors may play a role in preventing obesity in children and adolescents.

Cognition and its association with the factors of the EURO-D: Suffering and Motivation. Findings from SHARE Wave 6.

The aims of this study were (1) to analyse the relationship between cognition and clinical and sociodemographic variables, (2) to explore the relationship between cognitive tests and factors of EURO-D depression scale (Suffering and Motivation), and (3) to determine the relevance of cognition with respect to clinical and sociodemographic variables in the scores of the EURO-D factors. METHOD: About 63 755 participants in the Survey of Health, Ageing and Retirement in Europe (SHARE) Wave 6 (2015) were included. Instruments are as follows: the SHARE study, the EURO-D scale, and cognitive tests. Bivariate, correlation, and multiple linear regression analyses were performed. RESULTS: In the regression analysis with cognition, the variables associated with poor cognition were higher age (ß = .29), lower educational level (ß = -.26), economic difficulties (ß = .17), and depression (ß = .10). The correlation between cognition and EURO-D factors was weak in Suffering (r = -0.139) and moderate in Motivation (r = -0.382). In the regression analysis with the EURO-D, loneliness, poor self-perceived physical health, female gender, and low cognition were associated with higher depression levels. The main differences in the predictor variables of each factor were cognition (Motivation = -0.248, P < .001; Suffering = 0.002, P = .648) and the female sex (Motivation = 0.015, P < .001, Suffering = 0.175, P < .001). CONCLUSIONS: In the EURO-D depression scale, poor cognition was associated with higher scores in the Motivation factor only, while the female gender presented higher scores in the Suffering factor.

Cold-related mortality vs heat-related mortality in a changing climate: A case study in Vilnius (Lithuania).

INTRODUCTION: Direct health effects of extreme temperatures are a significant environmental health problem in Lithuania, and could worsen further under climate change. This paper attempts to describe the change in environmental temperature conditions that the urban population of Vilnius could experience under climate change, and the effects such change could have on excess heat-related and cold-related mortality in two future periods within the 21st century. METHODS: We modelled the urban climate of Vilnius for the summer and winter seasons during a sample period (2009-2015) and projected summertime and wintertime daily temperatures for two prospective periods, one in the near (2030-2045) and one in the far future (2085-2100), under the Representative Concentration Pathway (RCP) 8.5. We then analysed the historical relationship between temperature and mortality for the period 2009-2015, and estimated the projected mortality in the near future and far future periods under a changing climate and population, assuming alternatively no acclimatisation and acclimatisation to heat and cold based on a constant-percentile threshold temperature. RESULTS: During the sample period 2009-2015 in summertime we observed an increase in daily mortality from a maximum daily temperature of 30 °C (the 96th percentile of the series), with an average of around 7 deaths per year. Under a no acclimatisation scenario, annual average heat-related mortality would rise to 24 deaths/year (95% CI: 8.4-38.4) in the near future and to 46 deaths/year (95% CI: 16.4-74.4) in the far future. Under a heat acclimatisation scenario, mortality would not increase significantly in the near or in the far future. Regarding wintertime cold-related mortality in the sample period 2009-2015, we observed increased mortality on days on which the minimum daily temperature fell below - 12 °C (the 7th percentile of the series), with an average of around 10 deaths a year. Keeping the threshold temperature constant, annual average cold-related mortality would decrease markedly in the near future, to 5 deaths/year (95% CI: 0.8-7.9) and even more in the far future, down to 0.44 deaths/year (95% C: 0.1-0.8). Assuming a "middle ground" between the acclimatisation and non-acclimatisation scenarios, the decrease in cold-related mortality will not compensate the increase in heat-related mortality. CONCLUSION: Thermal extremes, both heat and cold, constitute a serious public health threat in Vilnius, and in a changing climate the decrease in mortality attributable to cold will not compensate for the increase in mortality attributable to heat. Study results reinforce the notion that public health prevention against thermal extremes should be designed as a dynamic, adaptive process from the inception.

Factor structure of depressive symptoms using the EURO-D scale in the over-50s in Europe. Findings from the SHARE project.

OBJECTIVES: The aims of this study are: to analyze the factor structure of the EURO-D depression scale; to explore the variables associated with depressive symptoms in the total sample and in the EURO-D factors; and to compare the presence of depressive symptoms and the factor distribution in 15 European countries. METHOD: 62,182 participants in Wave 5 (2013) of the Survey of Health, Aging and Retirement in Europe (SHARE) were included. INSTRUMENTS: The SHARE study and the EURO-D scale. Factor, bivariate and multilevel analyses were performed. RESULTS: Higher levels of depressive symptoms were associated with a poorer self-perception of physical health (η2 = 0.22) and economic difficulties (η2 = 0.07). Factor analysis of the EURO-D identified two factors: Suffering and Motivation. Higher levels of depressive symptoms were associated with female gender and younger age (≤60) in the Suffering factor, and with less activity and exercise, older age (≥71), widowhood and lower educational level in the Motivation factor. Poorer self-perception of physical health and economic difficulties were associated with higher depressive symptomatology in both factors. CONCLUSIONS: Poorer self-perception of physical health, female gender, economic difficulties, widowhood, lower levels of activity and exercise and lower educational level were associated with higher depressive symptomatology. In the countries of southern Europe, the Motivation factor predominated.

Kinship and cohabitation in relation to caregiver burden in the context of Alzheimer's disease: a 24-month longitudinal study.

OBJECTIVES: The aims of the study were to identify the clinical characteristics of three groups of caregivers: spouses, live-in adult-child or non-live-in adult-child, and their relation to the degree of perceived burden (Caregiver Burden Interview). METHODS: The sample comprised 275 Alzheimer's disease primary caregivers, with a follow-up of 24 months. Cognitive, functional and behavioural characteristics were evaluated in persons with dementia, whilst sociodemographic data, use of socio-medical resources, physical and mental health and self-perceived burden were assessed in caregivers. Generalized estimating equations were used for longitudinal data analysis. RESULTS: Spouse caregivers were 45.0% men, sole caregivers (>80%), used few external resources and had worse physical health. The number of female adult-child caregivers was higher (>75%). The live-in adult-child group, compared with the non-live-in adult-child group, was less likely to be married, had a lower level of education, was more commonly the sole caregiver and used fewer external resources. The greatest burden was observed in live-in adult-child caregivers, and the lowest in the non-live-in adult-child group, with no significant variation in the follow-up for both groups. Spouses had an intermediate level of perceived burden, which rose significantly during follow-up (p < 0.001). CONCLUSIONS: Kinship and cohabitation with the persons with dementia were associated with different scores and evolution of the burden, with an increase in the follow-up of the spouses, and with more or less burden, depending on cohabitation, in the adult-child groups. Interventions to reduce the level of burden on caregivers should consider these differences. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of noise on telephone calls to the Madrid Regional Medical Emergency Service (SUMMA 112).

BACKGROUND: Although the effects of noise on population morbidity and mortality have been observed both in the short and long term, the morbidity and mortality indicators used to date have not enabled information on such health effects to be accessed in real time. At an international level, there are relatively few studies, mostly recent, which have considered an alternative indicator, such as the demand for medical attention provided by emergency services, taking into account environmental factors other than noise. OBJECTIVES: To ascertain the short-term effect of road-traffic noise levels on medical care, broken down by organic, circulatory and respiratory causes, provided by the Madrid Regional Medical Emergency Service (Servicio de Urgencia Médica de Madrid/SUMMA 112). METHODS: We used an ecological time-series study and fitted Poisson regression models, to analyse the number of daily, cause-specific episodes of care provided in situ by SUMMA 112, via emergency ambulance dispatches, across the period 01/01/2008-31/12/2009. To this end, we considered diurnal (Leqd: 7-23h), nocturnal (Leqn: 23-7h) and daily (Leq24: 24h) noise (in db(A)) as the principal factor, and chemical air pollution (µg/m3) and temperature (°C) as the control variables. We also controlled for trend and seasonalities, the autoregressive nature of the series, and day of the week. RESULTS: Nocturnal noise exceeded the WHO threshold (55 db(A)) on 100% of nights, despite displaying a downward trend across the study period. For all causes, with the exception of emergency calls due to ischaemic disease, it was nocturnal rather than diurnal noise levels that had a short-term effect (lags 0-1) on SUMMA 112 calls, with this impact being greater for respiratory than for circulatory causes. Hence, for every increase of 1db in Leqn, the relative risks (RRs) were as follows: 1.11 (95% CI 1.09-1.13) for organic causes; 1.14 (95% CI: 1.11-1.18) for respiratory causes; and 1.08 (95% CI: 1.05-1.10) for circulatory causes. CONCLUSION: SUMMA 112 data give access to real-time information on the health effects associated with increases in noise levels, which cannot be obtained via mortality or hospital-admission data, since these are collected in the longer term. Accordingly, this is something that would be immediately applicable in any future implementation of a syndromic surveillance system focusing on the effects of environmental pollutants on health.