Social environment as a cause of litter loss in laboratory mouse: A behavioural study

Perinatal mortality is a widespread problem in laboratory mouse breeding and is often manifested by the loss of the entire litter within the first days of life. High mortality is an animal health and welfare concern that violates the 3R principles of reduction and refinement. High pup mortality is often considered “normal” in mouse breeding and the underlying causes are poorly understood. This study investigated the role of the social environment on pup survival and parental behaviour in C57BL/6 mice. Before parturition, multiparous females were allocated to three treatments: single-housing (SH, n=54) or group-housing in trios of two females and a male, with group-housing further divided into trios with (GH1, n=20) or without (GH0, n=35) the presence of another litter. Mouse behaviour was recorded from 24h before to 24h after parturition. Mouse breeding performance (offspring survival and weight) was analysed using logistic and generalized linear models, and behaviours using logistic and multivariable linear models. We confirmed previous findings of high mortality rates for all treatments, but the highest rates were found in GH1 where half of the litters were lost entirely. Social environment had an impact on breeding performance. On the one hand, the presence of adult cagemates in GH0 did not affect litter survival nor pup body weight at 20 days. Adult cagemates shared the work of breeding by performing nest building before and after litter birth, and parental care after birth. GH0 and GH1 dams were less frequently seen performing nest building before and after parturition than SH dams. GH0 and GH1 dams were also less frequently seen inside the nest and performing parental behaviour after parturition than were SH dams. On the other hand, the risks for litter and pup loss were dramatically increased by 2.3 and 1.8 times, respectively, in GH1 compared to GH0. Parturition lasted longer in GH1 than in GH0 treatment. While dam behaviour did not differ between GH1 and GH0, GH1 adult cagemates spent less time performing parental care than did GH0 cagemates. Plausible reasons for the higher mortality in the presence of another litter are insufficient parental care, competition for milk access, poor nest quality, and crushing of newborns by older pups in the nest. This study indicates that being born in a cage where there is already an older litter, so-called reproductive asynchrony, is a major risk factor for litter loss.The authors would like to thank Paula Sofia Vilares Gouveia and Sara Capas Peneda who participated in the behavioural analyses, and all the staff at the Biological Support Unit of the Babraham Institute for their interest and support in the project and the care of the animals. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/CVT-WEL/1202/2014 (POCI-01- 0145-FEDER-016591)

Outsourcing with debt financing

This paper investigates the effect of capital structure on a firm’s choice between vertical integration and outsourcing. We model the production decision in a Principal-Agent framework and show that suppliers use debt as a strategic instrument to collect the surplus from outsourcing as their wealth constraint or limited liability ensures them more attractive compensation schemes. Investigating the buyer’s capital structure, we find that outsourcing with risky debt is more likely to occur for high values of the outsourcing surplus.info:eu-repo/semantics/publishedVersio

A longitudinalidade e a integralidade no cuidado às crianças menores de um ano: avaliação de cuidadores

Objective: This study aimed to evaluate the attributes longitudinality and comprehensive care in Family Health Units in Vitória da Conquista, Bahia, Brazil. Method: quantitative, cross-sectional study with data collected through the use of the Brazilian version of Primary Care Assessment Tool. This instrument covers the essential attributes of the Primary Health Care, including longitudinality and comprehensive care. We interviewed 271 caretakers of children under one year old who use the health facilities, from January to June 2012. Results: longitudinality scores were high (3.07±0.53), demonstrating good experience of caretakers regarding the actions derived from this attribute. On the other hand, the scores for comprehensive care related to available services and services provided were low (2.83±0.36 and 2.81±0.98). Such results demonstrate little awareness of caretakers related to available services, as well as services provided to children by health facilities. Conclusions: Family Health Strategy is a reference for most health needs of the child; it promotes the relationship between caretakers and health professionals, and enables the knowledge about children health status. However, despite the high coverage of the Family Health Strategy in the county, some children´s health actions are not experienced by caretakers. Managers and health professionals should have the priorities for child health in their agendas, as well as planning and implementation of actions which are related to the child health needs.Objetivo: avaliar os atributos longitudinalidade e integralidade da atenção em Unidades de Saúde da Família em Vitória da Conquista, Bahia, Brasil. Método: pesquisa quantitativa, transversal com dados coletados mediante uso do Instrumento de Avaliação da Atenção Primária, versão nacional Primary Care Assessment Tool. Este instrumento contempla os atributos essenciais da APS, dentre eles a longitudinalidade e a integralidade da atenção. Foram entrevistados 271 cuidadores de crianças menores de um ano, usuários dos serviços, no período de janeiro a junho de 2012. Resultados: a longitudinalidade apresentou escore elevado (3,07±0,53), demonstrando boa experiência dos cuidadores com as ações derivadas desse atributo. Por outro lado, os escores para integralidade, tanto para serviços disponíveis quanto para serviços prestados, foram baixos (2,83±0,36 e 2,81±0,98). Tais resultados apontam pouca percepção dos cuidadores sobre serviços disponíveis, como também serviços prestados à criança pelas unidades de saúde. Conclusões: A ESF constitui referência para a maioria das necessidades de saúde da criança, favorece a relação entre cuidadores e profissionais, além de possibilitar o conhecimento da situação de saúde desse público. Entretanto, apesar da alta cobertura da estratégia no município, algumas ações em saúde voltadas às crianças não são vivenciadas pelos cuidadores. Aos gestores e profissionais de saúde que atuam com esta clientela, cabe a sensibilização sobre as prioridades dentro de suas agendas, como também o planejamento e a implementação de ações que estejam dentro das necessidades de saúde da população infantil

A mitotic recombination map proximal to the APC locus on chromosome 5q and assessment of influences on colorectal cancer risk

Mitotic recombination is important for inactivating tumour suppressor genes by copy-neutral loss of heterozygosity (LOH). Although meiotic recombination maps are plentiful, little is known about mitotic recombination. The APC gene (chr5q21) is mutated in most colorectal tumours and its usual mode of LOH is mitotic recombination.

Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in key disease regions, such as the pontine and dentate nuclei. Hsp90 inhibition has shown promising outcomes in some neurodegenerative diseases, but nothing is known about its effects in MJD. Chronic treatment of CMVMJD mice with Hsp90 inhibitor 17-DMAG resulted in a delay in the progression of their motor coordination deficits and, at 22 and 24 weeks of age, was able to rescue the uncoordination phenotype to wild-type levels; in parallel, a reduction in neuropathology was observed in treated animals. We observed limited induction of heat-shock proteins with treatment, but found evidence that 17-DMAG may be acting through autophagy, as LC3-II (both at mRNA and protein levels) and beclin-1 were induced in the brain of treated animals. This resulted in decreased levels of the mutant ataxin-3 and reduced intranuclear aggregation of this protein. Our data validate this novel mouse model as a relevant tool for the study of MJD pathogenesis and for pre-clinical studies, and show that Hsp90 inhibition is a promising therapeutic strategy for MJD.We would like to thank to Dr. Henry Paulson for providing the anti-ataxin-3 serum, Dr. Monica Sousa for the pCMV vector and to Eng. Lucilia Goreti Pinto, Lu s Martins, Miguel Carneiro and Celina Barros for technical assistance. This work was supported by Fundacao para a Ciencia e Tecnologia through the projects FEDER/FCT, POCI/SAU-MMO/60412/2004 and PTDC/SAU-GMG/64076/2006. This work was supported by Fundacao para a Ciencia e Tecnologia through fellowships SFRH/BPD/91562/2012 to A.S-F., SFRH/BD/78388/2011 to S. D-S., SFRH/BD/51059/2010 to A.N-C., and SFRH/BPD/79469/2011 to A.T-C.

The use of religious/spiritual coping among patients with cancer undergoing chemotherapy treatment

OBJECTIVE: to investigate the use of religious/spiritual coping among people with cancer undergoing chemotherapy. METHODS: a quantitative, descriptive and cross-sectional study of 101 patients undergoing intravenous chemotherapy in an oncology outpatients center in a public hospital in Minas Gerais, made in the first semester of 2011. For data collection, an interview was held, using a questionnaire for characterizing the sample and the Brief Spiritual/Religious Coping Scale. RESULTS: all subjects made use of religious/spiritual coping (mean=3.67; sd=0.37); the younger individuals, those with no religion and those who consider spiritual support unimportant tend to use coping negatively; individuals who would like to receive spiritual support and who participate in support groups for cancer patients, on the other hand, use coping positively. CONCLUSIONS: the study reinforces that religious/spiritual coping is an important strategy for coping with cancer, and contributes to an understanding of the same as a useful tool for spiritual care

Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model

One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential