The circadian rhythm of the perinatal mortality rate in Switzerland.

The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight-specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior.

Seasonal variation of overall and cardiovascular mortality: a study in 19 countries from different geographic locations.

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

Maternal mortality from hemorrhage in the State of Santa Catarina, Brazil

Hemorrhage represents a set of causes that focuses on women during the pregnancy and puerperal period, and that, with improper attention, results in death. The authors aimed to analyze maternal deaths related to hemorrhage that occurred in the state of Santa Catarina, Brazil. The data were obtained from the Mortality Information System and Live Births Information System from the Brazilian Ministry of Health. This was a descriptive study, in which 491 maternal deaths that occurred in the period 1997-2010 were analyzed. Of these, 61 were related to hemorrhage, corresponding to 12.42%; postpartum hemorrhage was the most prevalent cause, with 26 deaths, followed by placental abruption with 15, representing 67.21% of the cases. The maternal mortality from hemorrhage is a public health problem in the state of Santa Catarina, due to its high prevalence and the fact that its underlying causes are preventable.

Neonatal mortality in infants with low birth weigh

Objective To evaluate the factors associated with neonatal mortality in infant born with low birth weight. Method Cross-sectional study that analyzed data from 771 live births with low birth weight (<2500 g) in the city of Cuiabá, MT, in 2010, of whom 54 died in the neonatal period. We obtained data from the Information System on Live Births and Mortality, by integrated linkage. Results In multiple logistic regression, neonatal mortality was associated with: number of prenatal visits less than 7 (OR=3.80;CI:1,66-8,70); gestational age less than 37 weeks (OR=4.77;CI:1.48-15.38), Apgar score less than 7 at the 1st minute (OR=4.25;CI:1.84-9.81) and the 5th minute (OR=5.72,CI:2.24-14.60) and presence of congenital anomaly (OR=14.39;IC:2.72-76.09). Conclusion Neonatal mortality in infants with low birth weight is associated with avoidable factors through adequate attention to prenatal care, childbirth and infants.


A comparison of frailty of primary neurons, embryonic, and aging mouse cortical layers.

Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and superficial layers, were treated either with Aβ1-42, okadaic acid, or kainic acid. Second, whole E14 and E17 embryonic cortices, and third, in vitro separated deep and superficial layers of young and old C57BL/6J mice, were treated identically. We observed that E14 and E17 neurons in culture were prone to death after the Aβ and particularly the kainic acid treatment. This was also the case for the superficial layers of the aged cortex, but not for the embryonic, the young cortex, and the deep layers of the aged cortex. Thus, the aged superficial layers appeared to be preferentially vulnerable against Aβ and kainic acid. This pattern of vulnerability corresponds to enhanced accumulation of senile plaques in the superficial cortical layers with aging and Alzheimer's disease.

Inverse association between circulating vitamin D and mortality-dependent on sex and cause of death?

BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS: The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Dispersal strategies, few dominating or many coexisting: the effect of environmental spatial structure and multiple sources of mortality.

Interspecific competition, life history traits, environmental heterogeneity and spatial structure as well as disturbance are known to impact the successful dispersal strategies in metacommunities. However, studies on the direction of impact of those factors on dispersal have yielded contradictory results and often considered only few competing dispersal strategies at the same time. We used a unifying modeling approach to contrast the combined effects of species traits (adult survival, specialization), environmental heterogeneity and structure (spatial autocorrelation, habitat availability) and disturbance on the selected, maintained and coexisting dispersal strategies in heterogeneous metacommunities. Using a negative exponential dispersal kernel, we allowed for variation of both species dispersal distance and dispersal rate. We showed that strong disturbance promotes species with high dispersal abilities, while low local adult survival and habitat availability select against them. Spatial autocorrelation favors species with higher dispersal ability when adult survival and disturbance rate are low, and selects against them in the opposite situation. Interestingly, several dispersal strategies coexist when disturbance and adult survival act in opposition, as for example when strong disturbance regime favors species with high dispersal abilities while low adult survival selects species with low dispersal. Our results unify apparently contradictory previous results and demonstrate that spatial structure, disturbance and adult survival determine the success and diversity of coexisting dispersal strategies in competing metacommunities.

Female-biased mortality in experimentally parasitized Alpine Swift Apus melba nestlings

1. Sex-biased mortality in adult vertebrates is often attributed to lower immunocompetence and higher parasite susceptibility of males. Although sex-specific mortality has also been reported during growth, the importance of sex-specific immunocompetence and parasite susceptibility in explaining male-biased mortality remains ambiguous in growing individuals because of potentially confounding sources of mortality such as sexual dimorphism. 2. Here, we investigated sex-specific susceptibility to the blood-sucking louse fly Crataerina melbae and sex differences in cell-mediated immunity in a bird species that is sexually monomorphic both in size and plumage coloration at the nestling stage, the Alpine Swift, Apus melba. 3. For this purpose, we manipulated ectoparasite loads by adding or removing flies to randomly chosen nests in two years, and injected nestlings with mitogenic phytohaemagglutinin (PHA) in another year. 4. There were no significant differences between male and female offspring in immune response towards PHA, parasite load, and parasite-induced decrease in growth rate. Secondary sex ratios were however biased toward males in parasitized broods, and this was explained by a greater mortality of females in parasitized than deparasitized broods. 5. Our findings are in contrast to the widely accepted hypothesis that males suffer a greater cost of parasitism. We discuss alternative hypotheses accounting for female-specific mortality.

Association between valvular surgery and mortality among patients with infective endocarditis complicated by heart failure.

Context Heart failure (HF) is the most common complication of infective endocarditis. However, clinical characteristics of HF in patients with infective endocarditis, use of surgical therapy, and their associations with patient outcome are not well described.Objectives To determine the clinical, echocardiographic, and microbiological variables associated with HF in patients with definite infective endocarditis and to examine variables independently associated with in-hospital and 1-year mortality for patients with infective endocarditis and HF, including the use and association of surgery with outcome.Design, Setting, and Patients The International Collaboration on Endocarditis-Prospective Cohort Study, a prospective, multicenter study enrolling 4166 patients with definite native- or prosthetic-valve infective endocarditis from 61 centers in 28 countries between June 2000 and December 2006.Main Outcome Measures In-hospital and 1-year mortality.Results Of 4075 patients with infective endocarditis and known HF status enrolled, 1359 (33.4% [95% CI, 31.9%-34.8%]) had HF, and 906 (66.7% [95% CI, 64.2%-69.2%]) were classified as having New York Heart Association class III or IV symptom status. Within the subset with HF, 839 (61.7% [95% CI, 59.2%-64.3%]) underwent valvular surgery during the index hospitalization. In-hospital mortality was 29.7% (95% CI, 27.2%-32.1%) for the entire HF cohort, with lower mortality observed in patients undergoing valvular surgery compared with medical therapy alone (20.6% [95% CI, 17.9%-23.4%] vs 44.8% [95% CI, 40.4%-49.0%], respectively; P < .001). One-year mortality was 29.1% (95% CI, 26.0%-32.2%) in patients undergoing valvular surgery vs 58.4% (95% CI, 54.1%-62.6%) in those not undergoing surgery (P < .001). Cox proportional hazards modeling with propensity score adjustment for surgery showed that advanced age, diabetes mellitus, health care-associated infection, causative microorganism (Staphylococcus aureus or fungi), severe HF (New York Heart Association class III or IV), stroke, and paravalvular complications were independently associated with 1-year mortality, whereas valvular surgery during the initial hospitalization was associated with lower mortality.Conclusion In this cohort of patients with infective endocarditis complicated by HF, severity of HF was strongly associated with surgical therapy and subsequent mortality, whereas valvular surgery was associated with lower in-hospital and 1-year mortality.

Thyroid cancer mortality and incidence: a global overview.

In most areas of the world, thyroid cancer incidence has been appreciably increasing over the last few decades, whereas mortality has steadily declined. We updated global trends in thyroid cancer mortality and incidence using official mortality data from the World Health Organization (1970-2012) and incidence data from the Cancer Incidence in Five Continents (1960-2007). Male mortality declined in all the major countries considered, with annual percent changes around -2/-3% over the last decades. Only in the United States mortality declined up to the mid 1980s and increased thereafter. Similarly, in women mortality declined in most countries considered, with APCs around -2/-5% over the last decades, with the exception of the UK, the United States and Australia, where mortality has been declining up to the late 1980s/late 1990s to level off (or increase) thereafter. In 2008-2012, most countries had mortality rates (age-standardized, world population) between 0.20 and 0.40/100,000 men and 0.20 and 0.60/100,000 women, the highest rates being in Latvia, Hungary, the Republic of Moldova and Israel (over 0.40/100,000) for men and in Ecuador, Colombia and Israel (over 0.60/100,000) for women. In most countries, a steady increase in the incidence of thyroid cancer (mainly papillary carcinomas) was observed in both sexes. The declines in thyroid cancer mortality reflect both variations in risk factor exposure and changes in the diagnosis and treatment of the disease, while the increases in the incidence are likely due to the increase in the detection of this neoplasm over the last few decades.

Myocardial infarct size and mortality depend on the time of day-a large multicenter study.

BACKGROUND: Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry. METHODS: This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods. RESULTS: 6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00. DISCUSSION: As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Growth arrest-specific gene 6 » (Gas6) as an intra-hospital mortality predictor for patients in septic shock

Aim: Gas6 is known to be elevated in sepsis, correlating with the severity of infection and¦organ failure. We aimed to investigate the performance of Gas6 plasma levels at¦admission to predict the risk of mortality in a cohort of septic patients.¦Methods: We used prospectively collected data and plasma samples from the "Sepsis¦Cohorte Romande". Gas6 level was measured by ELISA at admission and expressed in¦percentage relative to its level in a pool of normal plasma.¦Results: Non-survivors (n=21) presented higher Gas6 levels than survivors (n=73) (median¦258% vs 164%, IQR 194 and 117 respectively) (p=0.0027). Gas6 correlated positively with¦different cytokines and was the best mortality predictor, as shown by the ROC curves area.¦In patients with septic shock (n=66), using 249% as a cut-off value, Gas6 measurement¦had a specificity of 67% and a sensitivity of 81% for predicting mortality. ROC curve area¦was 0.75. Positive and negative predictive values were 57% and 87%, respectively.¦Conclusion: Thus, Gas6 plasma level at admission might be a useful tool to predict¦mortality in patients with septic shock. Although Gas6 hold promise as an early sepsis¦marker, its precise implication in sepsis remains to be elucidated. Our observation should¦be further investigated in larger prospective clinical trials.

Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development.

The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS.

GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function.

GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8-/- mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na+ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations.

Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study.

OBJECTIVES: We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS: A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART.