Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State

BACKGROUND: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. AIM: To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)₂D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. MATERIAL AND METHODS: We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. RESULTS: Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. CONCLUSIONS: Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.&lt;p&gt;&lt;/p&gt; Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.&lt;p&gt;&lt;/p&gt; Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.&lt;p&gt;&lt;/p&gt; Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Animal abuse and intimate partner violence: researching the link and its significance in Ireland - a veterinary perspective

Research on domestic violence has established a substantial association between intimate partner abuse and the abuse of children within the home. It is only recently however, that researchers have demonstrated the correlation between non-accidental injury in animals, and abuse of women by their intimate male partners. A growing body of evidence suggests that animal abuse can be an early indicator for other forms of violent behaviour. This research includes the responses of a sample of 23 women using refuge services in the Republic of Ireland. It investigates the connection between domestic violence and animal abuse, and ascertains if there is sufficient support service for animals and people relevant to domestic abuse. In the survey population, 57% of women reported witnessing one or more forms of abuse, or threats of abuse, of their pets. Five of which were reported to have resulted in the death of the pet. Eighty seven per cent of women felt a facility to accommodate pets would have made their decision to leave the family home easier. Four women disclosed that lack of such a service and concern for the welfare of their companion animals caused them to remain in their abusive relationships for longer than they felt appropriate. Nine families placed pets in the care of family or friends, one woman is unaware of the fate of her pet, while the pets of six families remained with the abusive male after his partner entered a refuge. The majority of women felt unable to talk to anyone about their fears for their pets' welfare. Many felt that there is no service which can provide temporary accommodation for womens' pets while they are in refuge. The results obtained support those found elsewhere in larger studies in the USA and UK, and demonstrate an association of animal abuse in households where there is reported domestic violence

BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse

The BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage. There was a reduction in follicles number of BRE mutant (BRE(−/−)) mice. It was attributed to increase the follicular atresia in ovaries, as a result of retarded follicular development. We established that cell proliferation was inhibited, while apoptosis was markedly increased in the granulosa cells in the absence of BRE. In addition, expressions of γ-H2AX (marker for showing DNA double-strand breaks) and DNA damage-relevant genes are both upregulated in BRE(−/−) mice. In sum, these results suggest that the absence of BRE, deficiency in DNA damage repair, causes increased apoptosis in granulosa cells, which in turn induces follicular atresia in BRE(−/−) mice

The association between family and community social capital and health risk behaviours in young people: an integrative review

Background: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These ‘risky’ behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice.&lt;p&gt;&lt;/p&gt; Methods: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form.&lt;p&gt;&lt;/p&gt; Results: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent–child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk.&lt;p&gt;&lt;/p&gt; Conclusions: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.&lt;p&gt;&lt;/p&gt

The Safe Use of a PTEN Inhibitor for the Activation of Dormant Mouse Primordial Follicles and Generation of Fertilizable Eggs

Primordial ovarian follicles, which are often present in the ovaries of premature ovarian failure (POF) patients or are cryopreserved from the ovaries of young cancer patients who are undergoing gonadotoxic anticancer therapies, cannot be used to generate mature oocytes for in vitro fertilization (IVF). There has been very little success in triggering growth of primordial follicles to obtain fertilizable oocytes due to the poor understanding of the biology of primordial follicle activation.We have recently reported that PTEN (phosphatase and tensin homolog deleted on chromosome ten) prevents primordial follicle activation in mice, and deletion of Pten from the oocytes of primordial follicles leads to follicular activation. Consequently, the PTEN inhibitor has been successfully used in vitro to activate primordial follicles in both mouse and human ovaries. These results suggest that PTEN inhibitors could be used in ovarian culture medium to trigger the activation of primordial follicle. To study the safety and efficacy of the use of such inhibitors, we activated primordial follicles from neonatal mouse ovaries by transient treatment with a PTEN inhibitor bpV(HOpic). These ovaries were then transplanted under the kidney capsules of recipient mice to generate mature oocytes. The mature oocytes were fertilized in vitro and progeny mice were obtained after embryo transfer.Long-term monitoring up to the second generation of progeny mice showed that the mice were reproductively active and were free from any overt signs or symptoms of chronic illnesses. Our results indicate that the use of PTEN inhibitors could be a safe and effective way of generating mature human oocytes for use in novel IVF techniques

Obstetric and perinatal factors as predictors of child behaviour at 5 years

Objective To identify whether obstetric and perinatal factors are independent predictors of child behaviour at 5 years. Methodology The Mater University Study of Pregnancy (MUSP) is a prospective cohort study of 8556 mothers enrolled in early pregnancy. The relationship of obstetric and perinatal factors, maternal lifestyle, age and gender of the child, and social disadvantage were examined as predictors of child behaviour in 5005 children completing a modified child behaviour checklist at 5 years. This checklist contained three independent groups of behaviour: externalizng, internalizing and SAT (social, attentional and thought problems). Results In the initial analysis a limited number of associations were present. After adjusting for measures of social disadvantage, only number of antenatal admissions was associated with child behaviour in all three scales, while maternal cigarette smoking in pregnancy and male gender were associated with externalising and SAT behaviours. Conclusions Most common epidemiologic obstetric and perinatal risk factors were not independent predictors of behaviour problems in children at 5 years

Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging

<p>Abstract</p> <p>Background</p> <p>Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ).</p> <p>Methods</p> <p>Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes.</p> <p>Results</p> <p>Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes.</p> <p>Conclusion</p> <p>Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.</p

Is mitral valve repair superior to replacement for chronic ischemic mitral regurgitation with left ventricular dysfunction?

<p>Abstract</p> <p>Background</p> <p>This study was undertaken to compare mitral valve repair and replacement as treatments for ischemic mitral regurgitation (IMR) with left ventricular dysfunction (LVD). Specifically, we sought to determine whether the choice of mitral valve procedure affected survival, and discover which patients were predicted to benefit from mitral valve repair and which from replacement.</p> <p>Methods</p> <p>A total of 218 consecutive patients underwent either mitral valve repair (MVP, n = 112) or mitral valve replacement (MVR, n = 106). We retrospectively reviewed the clinical material, operation methods, echocardiography check during operation and follow-up. Patients details and follow-up outcomes were compared using multivariate and Kaplan-Meier analyses.</p> <p>Results</p> <p>No statistical difference was found between the two groups in term of intraoperative data. Early mortality was 3.2% (MVP 2.7% and MVR 3.8%). At discharge, Left ventricular end-systolic and end-diastolic diameter and left ventricular ejection fraction (LVEF) were improved more in the MVP group than MVR group (P < 0.05), however, in follow-up no statistically significant difference was observed between the MVR and MVP group (P > 0.05). Follow-up mitral regurgitation grade was significantly improved in the MVR group compared with the MVP group (P < 0.05). The Kaplan-Meier survival estimates at 1, 3, and 5 years were simlar between MVP and MVR group. Logistic regression revealed poor survival was associated with old age(#75), preoperative renal insufficiency and low left ventricular ejection fraction (< 30%).</p> <p>Conclusion</p> <p>Mitral valve repair is the procedure of choice in the majority of patients having surgery for severe ischemic mitral regurgitation with left ventricular dysfunction. Early results of MVP treatment seem to be satisfactory, but several lines of data indicate that mitral valve repair provided less long-term benefit than mitral valve replacement in the LVD patients.</p

Stability of Yellow Fever Virus under Recombinatory Pressure as Compared with Chikungunya Virus

Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4×106 in BHK-21 (vertebrate) cells and ∼1.05×105 in C710 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely