Comparative molecular genomic analyses of a spontaneous rhesus macaque model of mismatch repair-deficient colorectal cancer.

Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

A single dominant locus restricts retrovirus replication in YBR/Ei mice.

Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the anti-virus response in susceptible mice. Virus control is unrelated to virus-neutralizing antibodies, cytotoxic CD8+ T cells, NK cells, and NK T cells, which are the best characterized mechanisms of resistance to retroviruses. We identified a single, dominant locus that controls the resistance mechanism, which we provisionally named attenuation of virus titers (Avt) and mapped to the distal region of chromosome 18. IMPORTANCE Elucidation of the mechanism that mediates resistance to retroviruses is of fundamental importance to human health, as it will ultimately lead to knowledge of the genetic differences among individuals in susceptibility to microbial infections.

Excess potential years of working life lost in six countries from Latin America and Europe in 2020 and 2021.

OBJECTIVE: This descriptive study aimed to measure the excess all-cause mortality potential years of working life lost (PYWLL) in the working-age population of six Ibero-American countries in 2020 and 2021. METHODS: This study was based on all-cause deaths for the age group 15-69 years for men and women in six countries: Colombia, Costa Rica, México, Peru, Portugal and Spain. The expected PYWLL was the average value determined from the previous 5 years (2015-2019). To estimate the excess of PYWLL, the expected PYWLL was subtracted from the observed PYWLL values for 2020 and 2021, separately. RESULTS: In the four Latin American countries, the excess PYWLL per death was approximately double (between 12 and 16 years) that of the two European countries (between 3 and 9 years). CONCLUSIONS: The loss of working-age individuals will probably have a profound social and economic recovery impact, affecting families and communities. The informal employment and labour market structures may be contributing to the adverse effects of the pandemic in the region. Investing in universal, comprehensive and sustainable health and social protection systems in the Latin American countries is crucial to build resilience against current and future crises.

Labour market participation after sickness absence due to cancer: a dynamic cohort study in Catalonia (Spain).

BACKGROUND: The consequences of cancer on working until retirement age remain unclear. This study aimed to analyse working life considering all possible labour market states in a sample of workers after sickness absence (SA) due to cancer and to compare their working life paths to those of a sample of workers without SA and with an SA due to other diseases. METHODS: This was a retrospective dynamic cohort study among social security affiliates in Catalonia from 2012-2018. Cases consisted of workers with an SA due to cancer between 2012-2015 (N = 516) and were individually age- and sex-matched with those of affiliates with an SA due to other diagnoses and workers without an SA. All workers (N = 1,548, 56% women) were followed up from entry into the cohort until the end of 2018 to characterise nine possible weekly labour states. Sequence analysis, optimal matching, and multinomial logistic regression were used to identify and assess the probability of future labour market participation patterns (LMPPs). All analyses were stratified by sex. RESULTS: Compared with workers with an SA due to cancer, male workers with no SA and SA due to other causes showed a lower probability of being in the LMPP of death (aRRR 0.02, 95% CI: 0.00‒0.16; aRRR 0.17, 95% CI: 0.06‒0.46, respectively) and, among women, a lower probability of permanent disability and death (aRRR 0.24, 95% CI: 0.10‒0.57; aRRR 0.39, 95% CI: 0.19‒0.83, respectively). Compared to workers with SA due to cancer, the risk of early retirement was lower among workers with no SA (women, aRRR 0.60, 95% CI: 0.22‒1.65; men, aRRR 0.64, 95% CI: 0.27‒1.52), although these results were not statistically significant. CONCLUSIONS: Workplaces, many of which have policies common to all diagnoses, should be modified to the needs of cancer survivors to prevent an increasing frequency of early retirement and permanent disability when possible. Future studies should assess the impact of cancer on premature exit from the labour market among survivors, depending on cancer localisation and type of treatment.

LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses.

LRRC8 family proteins on the plasma membrane play a critical role in cellular osmoregulation by forming volume-regulated anion channels (VRACs) necessary to prevent necrotic cell death. We demonstrate that intracellular LRRC8 proteins acting within lysosomes also play an essential role in cellular osmoregulation. LRRC8 proteins on lysosome membranes generate large lysosomal volume-regulated anion channel (Lyso-VRAC) currents in response to low cytoplasmic ionic strength conditions. When a double-leucine L706L707 motif at the C terminus of LRRC8A was mutated to alanines, normal plasma membrane VRAC currents were still observed, but Lyso-VRAC currents were absent. We used this targeting mutant, as well as pharmacological tools, to demonstrate that Lyso-VRAC currents are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis. Thus, Lyso-VRACs allow lysosomes of mammalian cells to act as the cell`s "bladder." When Lyso-VRAC current was selectively eliminated, the extent of necrotic cell death to sustained stress was greatly increased, not only in response to hypoosmotic stress, but also to hypoxic and hypothermic stresses. Thus Lyso-VRACs play an essential role in enabling cells to mount successful homeostatic responses to multiple stressors.

Naked (N) mutant mice carry a nonsense mutation in the homeobox of Hoxc13.

Loss of function mutations in HOXC13 have been associated with Ectodermal Dysplasia-9, Hair/Nail Type (ECTD9) in consanguineous families, characterized by sparse to complete absence of hair and nail dystrophy. Here we characterize the spontaneous mouse mutation Naked (N) as a terminal truncation in the Hoxc13 (homeobox C13) gene. Similar to previous reports for homozygous Hoxc13 knock-out (KO) mice, homozygous N/N mice exhibit generalized alopecia with abnormal nails and a short lifespan. However, in contrast to Hoxc13 heterozygous KO mice, N/+ mice show generalized or partial alopecia, associated with loss of hair fibres, along with normal lifespan and fertility. Our data point to a lack of nonsense-mediated Hoxc13 transcript decay and the presence of the truncated mutant protein in N/N and N/+ hair follicles, thus suggesting a dominant-negative mutation. To our knowledge, this is the first report of a semi-dominant and potentially dominant-negative mutation affecting Hoxc13/HOXC13. Furthermore, recreating the N mutant allele in mice using CRISPR/Cas9-mediated genome editing resulted in the same spectrum of deficiencies as those associated with the spontaneous Naked mutation, thus confirming that N is indeed a Hoxc13 mutant allele. Considering the low viability of the Hoxc13 KO mice, the Naked mutation provides an attractive new model for studying ECTD9 disease mechanisms.

[Excess mortality in 2020 in the working-age population of nine Latin American countriesExcesso de mortalidade na população em idade ativa em nove países da América Latina no ano de 2020]. / Exceso de mortalidad en población en edad de trabajar en nueve países de Latinoamérica, año 2020.

Objective: Estimate the impact of the COVID-19 pandemic in 2020, through excess all-cause mortality and potential years of productive life lost (YPLL) in the working-age population, in selected Latin American and Caribbean countries. Methods: Study based on data on deaths from all causes from age 15 to 69 years, mainly from national institutes of statistics. Estimates of expected deaths were based on reported deaths from 2015 to 2019. Excess mortality was estimated using the P indicator, standardized mortality ratio (SMR), and potential YPLL up to age 70 years. Results: Excess deaths in Brazil, Bolivia, Chile, Colombia, Costa Rica, Cuba, the Dominican Republic, Mexico, and Peru totaled 426 978 (279 591 men and 147 438 women), representing a potential loss of 5 710 048 (3 738 775 in men and 1 971 273 in women) years of productive life. Observed mortality was significantly higher than expected in all countries except the Dominican Republic. Conclusions: COVID-19 in the working-age population will have a profound impact on socio-economic conditions. Timely counting of excess deaths is useful and can be used as an early warning system to monitor the magnitude of COVID-19 outbreaks. Monitoring of excess mortality in working-age people by the Ibero-American Observatory on Safety and Health at Work enables more accurate assessment of the social and economic burden of COVID-19.

Objetivo: Estimar o impacto da pandemia de COVID-19 durante o ano de 2020, por meio do excesso de mortalidade por todas as causas e dos anos produtivos de vida perdidos (APrVP) na população em idade ativa, em uma seleção de países da América Latina e do Caribe. Métodos: Estudo baseado em dados de óbitos por todas as causas entre 15 e 69 anos, principalmente dos Institutos Nacionais de Estatística. Os óbitos esperados foram estimados a partir daqueles registrados entre 2015 e 2019. O excesso de mortalidade foi estimado por meio do indicador P, da razão de mortalidade padronizada (RMP) e dos APrVP até os 70 anos. Resultados: O excesso de óbitos no Brasil, na Bolívia, no Chile, na Colômbia, na Costa Rica, em Cuba, no México, no Peru e na República Dominicana totalizou 426 978 (279 591 em homens e 147 438 em mulheres), o que representou uma perda de 5 710 048 (3 738 775 em homens e 1 971 273 em mulheres) APrVP. A mortalidade observada foi significativamente maior do que o esperado em todos os países, exceto na República Dominicana. Conclusões: O impacto da COVID-19 na população em idade ativa terá um impacto profundo na situação socioeconómica. O cálculo oportuno do excesso de mortes é útil e pode ser usado como um sistema de alerta precoce para monitorar a magnitude dos surtos de COVID-19. O monitoramento do excesso de mortalidade em pessoas em idade ativa, realizado pelo Observatório Ibero-Americano de Segurança e Saúde no Trabalho, permite avaliar com mais precisão a carga social e econômica da COVID-19.

Monitoring Self-Perceived Occupational Health Inequities in Central America, 2011 and 2018.

Objectives. To analyze changes in occupational health inequity between 2011 and 2018 among workers in Central America. Methods. Data were collected by face-to-face interviews at the workers' homes for the 2 Central America Working Conditions Surveys (n = 12 024 in 2011 and n = 9030 in 2018). We estimated health inequity gaps by means of absolute and relative population attributable risks and the weighted Keppel index. We stratified all analyses by gender. Results. Between 2011 and 2018, the proportion of workers reporting poor self-perceived health decreased both in women (from 32% to 29%) and men (from 33% to 30%). However, the health inequity gaps remained wide in the 4 stratifiers. Measured by the Keppel index, health inequity gaps between countries increased from 22% to 39% in women and from 20% to 29% in men. Conclusions. While health improved between 2011 and 2018, health inequity gaps remained wide. Wider health inequity gaps were observed between countries than by gender, age, occupation, or education. Public Health Implications. This first benchmark of occupational health inequities in Central America could be useful when developing and evaluating the impact of public policies on work.

Informal employment and poor self-perceived health in Latin America and the Caribbean: a gender-based comparison between countries and welfare states in a pooled analysis of 176,786 workers.

BACKGROUND: More than half of the working population in Latin American and Caribbean (LAC) countries is engaged in informal employment. The few previous studies indicate that this employment condition could have negative consequences for workers' health. The aim of the present study was to estimate the association between self-perceived health and informality in LAC countries according to gender and welfare state type. METHODS: The cross-sectional study based on different working conditions and health national surveys was carried out in 13 LAC countries between 2012 and 2018. A sample of 176,786 workers was selected from these surveys. The association between health and informality was estimated using Poisson regression. Finally, a random effects meta-analysis was carried out by country. All results were stratified by sex and type of welfare state (statalist or familialist). RESULTS: Informal workers reported significantly worse health than formal workers, for both women (1.28 [95% CI 1.14-1.43]) and men (1.30 [1.12-1.50]). This difference was broader and more significant in countries with statalist welfare state regimes, among both women (1.40 [1.22-1.60]) and men (1.51 [1.30-1.74]), than in familialist regime countries (1.19 [1.03-1.38] and 1.24 [1.03-1.49], respectively). CONCLUSIONS: This study provides strong evidence of the association between informal employment and worker health. Welfare states appear to have a modifying effect on this association. The transition from the informal to the formal labour market in LAC is essential to improving the health of the population.

MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

Health inequity in workers of Latin America and the Caribbean.

BACKGROUND: Latin America and the Caribbean (LAC) is the world's most inequitable region in terms of wealth distribution. The full scale of social inequalities in health has been hidden by the lack of reliable data. This study aimed to measure and compare health inequalities in the working population within and between 15 countries of LAC. METHODS: A sample of 180,163 workers aged 18 years and older was drawn from the most recent national surveys of working conditions or health in 15 LAC countries. Poor self-perceived health (P-SPH) was used as a health indicator, and age, education level, and occupational category as inequality stratifiers. We calculated four measures: absolute and relative population-attributable risks, the Kuznets and weighted Keppel indexes. RESULTS: P-SPH prevalence ranged from 9% in men from Uruguay to 50% in women from Nicaragua. It was higher in women than in men in most countries. A clear gradient was shown, in which young people in non-manual skilled jobs and high education had the lowest prevalence. Nearly 45% of cases that reported P-SPH among men and 35% among women could be avoided if all the groups received a higher level of education. Also, approximately 42% of P-SPH reported by men and 31% by women could be avoided if they all shared the working and employment conditions of non-manual skilled jobs. CONCLUSIONS: Wide health inequalities were found between occupational and educational groups in LAC. However, country borders appear to be an even more important stratifier in the production of health inequalities. Urgent interventions to improve worker's health are needed in countries where prevalence of poor self-perceived health is high. Strengthening occupational health surveillance system in LAC countries should become a priority, in order to track the interventions to reduce occupational health inequity.

Sickness absence trajectories following labour market participation patterns: a cohort study in Catalonia (Spain), 2012-2014.

BACKGROUND: Previous studies have focused on the relationship between employment pathways and health-related outcomes based on cross-sectional or longitudinal approaches. However, little is known about the cumulative effects of employment status mobility on sickness absence (SA) over time. The aim of the present study was to examine the association between prior labour market participation (LMP) patterns and SA trajectories from a life-course perspective. METHODS: This cohort study was based on a sample of 11,968 salaried workers living in Catalonia and affiliated with the Spanish Social Security system, who accumulated more than 15 days on SA in at least one quarter during 2012-2014. Individuals were grouped into three different working life stages: early (18-25 years), middle (26-35 years), and late (36-45 years). To identify LMP patterns, we applied sequence analysis and cluster analysis (2002-2011), and we used latent class growth modelling to identify SA trajectories (2012-2014). Finally, we applied multinomial logistic regression models to assess the relationship between LMP patterns and SA trajectories. RESULTS: The analyses yielded six LMP patterns: stable employment (value range: 63-81%), increasing employment (5-22%), without long-term coverage (7-8%), decreasing employment (4-10%), fluctuant employment (13-14%), and steeply decreasing employment (7-9%). We also identified four SA trajectories: low stable (83-88%), decreasing (5-9%), increasing (5-11%), and high stable (7-16%). However, the only significant association we identified for LMP patterns and SA trajectories was among young men, for whom an increasing employment pattern was significantly associated with a lower risk for increased days on SA (adjusted odds ratio: 0.21; 95% confidence interval: 0.05-0.96). CONCLUSIONS: SA trajectories are generally not related to prior 10-year LMP patterns at any stage of working life. To disentangle this relationship, future research might benefit from considering working life transitions with a quality-of-work approach framed with contextual factors closer to the SA course.

Correction to: Sickness absence trajectories following labour market participation patterns: a cohort study in Catalonia (Spain), 2012-2014.

An amendment to this paper has been published and can be accessed via the original article.

Working conditions and absence from work during pregnancy in a cohort of healthcare workers.

OBJECTIVES: To assess the relationship between exposure to occupational risk factors during pregnancy and absence from work using two different social benefits. METHOD: Three working pregnancy trajectories (WPT) were identified in a cohort of 428 pregnant workers from a healthcare institution (period 2010-2014), based on absence days and using cluster analysis. WPT1 included absences mainly covered by sickness absence benefit (32.0% of women), WPT2 included absences covered by pregnancy occupational risk (POR) benefit (28.3%) and WPT3 were pregnant workers with few absences (39.9%). Exposure to occupational risk factors was assessed by experts and association with trajectories was analysed using logistic regression. Relative risks (RR) and their 95% CIs were adjusted for age, type of contract and shift work. RESULTS: WPT2 was associated with exposure to physical (RR=1.86, 95%CI 1.17 to 2.97), safety (RR=2.10, 95%CI 1.61 to 2.73), ergonomic (RR=2.52, 95%CI 1.89 to 3.36) and psychosocial (RR=1.79, 95%CI 1.31 to 2.46) factors, and with exposure level. For physicians, WPT1 was associated with safety risks (RR=3.13, 95%CI 1.22 to 7.99), WPT2 with chemical and ergonomic for administrative/technical support (RR=12.20, 95%CI 1.69 to 88.09; RR=14.09, 95%CI 1.34 to 148.61, respectively), with safety and ergonomic risks for nursing aides (RR=1.84, 95%CI 1.12 to 3.02; RR=3.94, 95% CI 2.38 to 6.53, respectively), and with physical (RR=1.72, 95%CI 1.04 to 2.86), safety (RR=2.21, 95%CI 1.62 to 3.03), ergonomic (RR=2.02, 95%CI 1.44 to 2.86) and psychosocial factors (RR=1.96, 95%CI 1.32 to 2.90) for nurses. CONCLUSIONS: Absences from work covered by POR benefit show a consistent relationship with exposure to occupational risks. Sickness absence is the most frequent benefit used by pregnant workers. Current social benefits are apparently used adequately for protecting women from occupational exposures. Future studies are needed to clarify this further.

A hospital occupational diseases unit: an experience to increase the recognition of occupational disease.

BACKGROUND: Under-reporting and recognition of occupational diseases is a problem in countries with workers' compensation schemes. OBJECTIVE: To describe the role of a public hospital Occupational Disease Unit (ODU) in Barcelona that resulted in improved reporting and official recognition of occupational diseases from 2010 to 2017. METHODS: Hospital physicians referred possible cases of work-related disease to the ODU, where in-depth medical evaluations were then performed, and a detailed report addressing causation was generated. Patients with confirmed cases of occupational disease were counselled and followed while pursuing official recognition and benefits claims by the Spanish Social Security System. RESULTS: Between 2010 and 2017, 149 cases were referred to the ODU for evaluation. Of these, 80 (53.7%) were confirmed to have an occupational disease, 54 (67.5%) patients pursued official recognition, and to date 26 (48.1%) have been recognized by the Social Security System. The recognition rate varied by diagnosis group (p=0.003), and was highest for skin diseases (71.4%) and cancer (66.7%), and lowest for hearing loss (29.4%) and musculoskeletal disorders (16.7%). CONCLUSIONS: A hospital ODU can improve reporting and official recognition of occupational diseases that otherwise might not have been recognized. Expanding this experience to other Spanish and European hospitals could improve the efficiency of workers' compensation schemes and better support preventive policies.

[Proposed indicators for occupational health surveillance in Latin America and the CaribbeanProposta de indicadores para vigilância em saúde ocupacional na América Latina e Caribe]. / Propuesta de indicadores para la vigilancia de la salud ocupacional en América Latina y el Caribe.

This article proposes a set of common basic indicators for occupational health surveillance in the region of Latin America and the Caribbean and identifies the sources of data that are available for their measurement. To this end, consensus was built among members of the Expert Network on Working, Employment, and Health Conditions Surveys (RED ECoTES) in two stages. In the first stage, a preliminary list of indicators was agreed upon; in the second stage, data sources and their characteristics were identified to help determine the feasibility of measuring the actual value of each indicator in 20 countries of the region. The proposed set of basic indicators, together with their definitions, is composed of 13 indicators in four areas: employment conditions (three indicators), working conditions (four indicators), resources and preventive activities (two indicators), and health (four indicators). The primary sources of data available in the region for calculating these indicators were: permanent household surveys; surveys on conditions of work, employment, and health; vital statistics; and reporting systems for occupational injuries. Data are available in the region for many of the proposed indicators, but a sizable number of those having to do with working conditions and preventive activities are not available in most countries. For effective occupational health surveillance in the region, surveys on conditions of work, employment, and health must be vigorously promoted in each country.

Neste artigo é proposto um conjunto básico de indicadores comuns para vigilância em saúde ocupacional na América Latina e Caribe, com a identificação das fontes de dados disponíveis para mensuração destes indicadores. A Rede Latino-Americana de Especialistas em Inquéritos sobre Condições de Trabalho, Emprego e Saúde (REDE ECoTES) conduziu um processo de decisão por consenso em duas etapas. A primeira etapa consistiu da seleção inicial dos indicadores e a segunda etapa compreendeu a identificação das fontes de dados e suas características, com o propósito de facilitar comprovar a viabilidade do cálculo efetivo de cada indicador em 20 países da Região. É proposto um conjunto básico de indicadores e respectivas definições contendo 13 indicadores distribuídos em quatro dimensões: condições de emprego (três indicadores), condições de trabalho (quatro indicadores) e recursos e atividades de prevenção (dois indicadores) e saúde (quatro indicadores). As principais fontes disponíveis na Região para determinar os indicadores são: as pesquisas permanentes de domicílios, as pesquisas sobre as condições de trabalho, emprego e saúde, as estatísticas vitais e os sistemas de notificação de acidentes de trabalho. Existem dados disponíveis para o cálculo de um número relevante dos indicadores propostos. Porém, a maioria dos países não dispõe de dados para calcular um número importante dos indicadores relacionados às condições de trabalho e atividades de prevenção. A vigilância efetiva em saúde ocupacional requer um firme incentivo às pesquisas sobre as condições de emprego, trabalho e saúde em cada país da Região.

Leucine-rich repeat containing 8A (LRRC8A)-dependent volume-regulated anion channel activity is dispensable for T-cell development and function.

BACKGROUND: Leucine-rich repeat containing 8A (LRRC8A) is an ubiquitously expressed transmembrane protein with 17 leucine-rich repeats (LRRs) at its C-terminal end and is an essential component of the volume-regulated anion channel (VRAC), which controls cellular volume. A heterozygous mutation in LRRC8A that truncates the 2 terminal LRRs was reported in a patient with agammaglobulinemia and absent B cells and was demonstrated to exert a dominant negative effect on T- and B-cell development in mice. Lrrc8a-/- mice have severely defective T-cell development and function. It is not known whether the T- and B-cell defects caused by LRRC8A deficiency are caused by loss of VRAC activity. OBJECTIVE: We sought to determine whether VRAC activity is required for normal T-cell development and function. METHODS: VRAC activity was examined by using patch-clamp analysis. Flow cytometry was used to examine T-cell development. T-cell proliferation, cytokine secretion, and antibody titers were measured by using standard techniques. RESULTS: We demonstrate that the spontaneous mouse mutant ébouriffé (ebo/ebo) harbors a homozygous 2-bp frameshift mutation in Lrrc8a that truncates the 15 terminal LRRs of LRRC8A. The Lrrc8aebo mutation does not affect protein expression but drastically diminishes VRAC activity in T cells. ebo/ebo mice share features with Lrrc8a-/- mice that include curly hair, infertility, reduced longevity, and kidney abnormalities. However, in contrast to Lrrc8a-/- mice, ebo/ebo mice have normal T-cell development and function and intact antibody response to T-dependent antigen. CONCLUSION: LRRC8A-dependent VRAC activity is dispensable for T-cell development and function.

The Length of Working Life in Spain: Levels, Recent Trends, and the Impact of the Financial Crisis.

While there has been considerable debate about extending the length of working life, relatively little is known about this issue. We use data from the Spanish Continuous Working Life Sample for 2004-2013 to calculate period working life tables, which in turn allows us to assess the impact of the financial crisis on working life expectancy in Spain. Before the recession hit, working life expectancy in Spain was around 38 years for males and 33 years for females. The recession had a tremendous impact on the Spanish labor market, but the effects differed considerably by gender and occupational category. Men working in skilled non-manual jobs were less affected, while men working in unskilled manual jobs lost close to 14 years of working life expectancy. Women were less affected than men. With working life expectancy decreasing, the average proportion of lifetime spent in unemployment and outside the labor market increased markedly, whereas the average number of years spent in retirement changed only a little. When we decompose losses in working life expectancy by age group, we find that economic fluctuations affect both older and younger workers. This result suggests that policies that focus on retirement ages only are incomplete. We also compare our findings to the results obtained by Sullivans method, which is based on prevalence rates rather than the incidence-based working life table approach. We find that the use of Sullivans approach does not accurately reflect the levels of and the trends in working life expectancy.

Influence of paid maternity leave on return to work after childbirth.

BACKGROUND: Paid maternity leave (ML) has been associated with better health outcomes in mothers and newborns. However, its protective role in mothers' employment after childbirth remains unclear. OBJECTIVE: To assess the association between paid ML and being employed 1-year after childbirth. METHODS: As part of the INfancia y Medio Ambiente (INMA) cohort study, 507 Spanish women employed at 12th week of pregnancy, were asked about their employment status and job characteristics at 32nd week of pregnancy. One year after childbirth, they were re-interviewed about their employment status and if they had taken paid ML. Incidence of maternal employment 1-year after childbirth was estimated. Crude and adjusted associations with paid ML were assessed by logistic regression, and characterized by odds ratios (ORs) with associated 95% CIs. RESULTS: Information was obtained from 398 women. Of those, 290 (72.9%) were employed 1-year after childbirth. Incidence of maternal employment was lower for those who: i) didn't take paid ML, ii) were younger than 27 years; iii) had temporary contract, iv) had part-time jobs, v) reported less-favoured familiar social class, and vi) left the job before 32 weeks of pregnancy. Being employed 1-year after childbirth was more common in those who took paid ML (OR 2.7, 95%CI 1.6-4.5), also after adjusting for staying at work until advanced stages of pregnancy (OR 1.8, 95%CI 1.0-3.1). CONCLUSIONS: Taking paid ML seems to be associated with higher maternal employment rates 1-year after childbirth. Therefore, our findings suggest that protection of maternity might positively influence women's labour market participation after childbirth.