Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Individually ventilated caging (IVC) systems for rodents are increasingly common in laboratory animal facilities. However, the impact of such substantial change in housing conditions on animal physiology and behavior is still debated. Most importantly, there arise the questions regarding reproducibility and comparison of previous or new phenotypes between the IVC and open cages. The present study was set up for detailed and systematic comparison of behavioral phenotypes in male and female mice of three widely used inbred strains (C57BL/6JRccHsd, DBA/2JRccHsd, 129S2/SvHSd) after being kept in two housing environments (IVC and open cages) for 6?weeks (since 4?weeks of age) before behavioral testing. The tests addressed exploratory, anxiety-like and stress-related behavior (light-dark box, open field, forced swim test, stress-induced hyperthermia), social approach and species-specific behavior (nest building, marble burying). In all tests, large and expected strain differences were found. Somewhat surprisingly, the most striking effect of environment was found for basal body temperature and weight loss after one night of single housing in respective cages. In addition, the performance in light-dark box and open field was affected by environment. Several parameters in different tests showed significant interaction between housing and genetic background. In summary, the IVC housing did not invalidate the well-known differences between the mouse strains which have been established by previous studies. However, within the strains the results can be influenced by sex and housing system depending on the behavioral tasks applied. The bottom-line is that the environmental conditions should be described explicitly in all publications.Peer reviewe

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice

ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease

Anthropometric measures in relation to Basal Cell Carcinoma: a longitudinal study

BACKGROUND: The relationship between anthropometric indices and risk of basal cell carcinoma (BCC) is largely unknown. We aimed to examine the association between anthropometric measures and development of BCC and to demonstrate whether adherence to World Health Organisation guidelines for body mass index, waist circumference, and waist/hip ratio was associated with risk of BCC, independent of sun exposure. METHODS: Study participants were participants in a community-based skin cancer prevention trial in Nambour, a town in southeast Queensland (latitude 26°S). In 1992, height, weight, and waist and hip circumferences were measured for all 1621 participants and weight was remeasured at the end of the trial in 1996. Prevalence proportion ratios were calculated using a log-binomial model to estimate the risk of BCC prior to or prevalent in 1992, while Poisson regression with robust error variances was used to estimate the relative risk of BCC during the follow-up period. RESULTS: At baseline, 94 participants had a current BCC, and 202 had a history of BCC. During the 5-year follow-up period, 179 participants developed one or more new BCCs. We found no significant association between any of the anthropometric measures or indices and risk of BCC after controlling for potential confounding factors including sun exposure. There was a suggestion that short-term weight gain may increase the risk of developing BCC for women only. CONCLUSION: Adherence to World Health Organisation guidelines for body mass index, waist circumference and waist/hip ratio is not significantly associated with occurrence of basal cell carcinomas of the skin

Factors associated with tocolytic hospitalizations in Taiwan: evidence from a population-based and longitudinal study from 1997 to 2004

<p>Abstract</p> <p>Background</p> <p>The use of tocolytic hospitalization in antenatal care is controversial and worthy of more research. We investigated individual, institutional, and area factors that affect the use of tocolytic hospitalizations in Taiwan where fertility has rapidly declined.</p> <p>Methods</p> <p>Longitudinal data from the 1996 to 2004 National Health Insurance Research Database in Taiwan were used to identify tocolytic hospitalizations. The probit model was used to estimate factors associated with tocolytic hospitalizations.</p> <p>Results</p> <p>The decline in fertility was significantly associated with the probability of tocolytic hospitalizations. Several physician and institutional factors-including physician's age, hospital ownership, accreditation status, bed size, and teaching status-were also significantly correlated to the dependent variables.</p> <p>Conclusions</p> <p>The provision of inpatient tocolysis is influenced not only by clinical considerations but also by physician, institutional, and area factors unrelated to clinical need. Fertility declines in Taiwan may have led obstetricians/gynecologists to provide more tocolysis to make up for their lost income. If the explanation is further validated, reimbursement policies may need to be reviewed to correct for overuse of inpatient tocolysis. The correlation could also be explained by the increasing use of artificial reproductive technologies and higher social value of newborns. In addition, the physician and institutional variations observed in the study indicate potential misuse of inpatient tocolysis that warrant further investigation.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Fractures in myelomeningocele

BACKGROUND: In patients with myelomeningocele (MMC), a high number of fractures occur in the paralyzed extremities, affecting mobility and independence. The aims of this retrospective cross-sectional study are to determine the frequency of fractures in our patient cohort and to identify trends and risk factors relevant for such fractures. MATERIALS AND METHODS: Between March 1988 and June 2005, 862 patients with MMC were treated at our hospital. The medical records, surgery reports, and X-rays from these patients were evaluated. RESULTS: During the study period, 11% of the patients (n = 92) suffered one or more fractures. Risk analysis showed that patients with MMC and thoracic-level paralysis had a sixfold higher risk of fracture compared with those with sacral-level paralysis. Femoral-neck z-scores measured by dual-energy X-ray absorptiometry (DEXA) differed significantly according to the level of neurological impairment, with lower z-scores in children with a higher level of lesion. Furthermore, the rate of epiphyseal separation increased noticeably after cast immobilization. Mainly patients who could walk relatively well were affected. CONCLUSIONS: Patients with thoracic-level paralysis represent a group with high fracture risk. According to these results, fracture and epiphyseal injury in patients with MMC should be treated by plaster immobilization. The duration of immobilization should be kept to a minimum (<4 weeks) because of increased risk of secondary fractures. Alternatively, patients with refractures can be treated by surgery, when nonoperative treatment has failed

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

The development and preliminary psychometric properties of two positive psychology outcome measures for people with dementia: the PPOM and the EID-Q.

Background: Positive psychology research in dementia care has largely been confined to the qualitative literature because of the lack of robust outcome measures. The aim of this study was to develop positive psychology outcome measures for people with dementia. Methods: Two measures were each developed in four stages. Firstly, literature reviews were conducted to identify and operationalise salient positive psychology themes in the qualitative literature and to examine existing measures of positive psychology. Secondly, themes were discussed within a qualitative study to add content validity for identified concepts (n = 17). Thirdly, draft measures were submitted to a panel of experts for feedback (n = 6). Finally, measures were used in a small-scale pilot study (n = 33) to establish psychometric properties. Results: Salient positive psychology themes were identified as hope, resilience, a sense of independence and social engagement. Existing measures of hope and resilience were adapted to form the Positive Psychology Outcome Measure (PPOM). Due to the inter-relatedness of independence and engagement for people with dementia, 28 items were developed for a new scale of Engagement and Independence in Dementia Questionnaire (EID-Q) following extensive qualitative work. Both measures demonstrated acceptable internal consistency (α = .849 and α = .907 respectively) and convergent validity. Conclusions: Two new positive psychology outcome measures were developed using a robust four-stage procedure. Preliminary psychometric data was adequate and the measures were easy to use, and acceptable for people with dementia

The Role of Health Systems Factors in Facilitating Access to Psychotropic Medicines: A Cross-Sectional Analysis of the WHO-AIMS in 63 Low- and Middle-Income Countries

In a cross-sectional analysis of WHO-AIMS data, Ryan McBain and colleagues investigate the associations between health system components and access to psychotropic drugs in 63 low and middle income countries