During the early postpartum period dairy cows mobilize fat and muscle to support lactation. This is associated with alterations in blood metabolite and hormone profiles which in turn influence milk yield and fertility. This study developed models to determine how metabolic traits, milk yield and body condition score were inter-related at different times in the periparturient period and to compare these relationships in primiparous (PP, n=188) and multiparous (MP, n=312) cows. Data from four previous studies which included information on blood metabolic parameters, parity, milk yield, body condition score and diet were collated into a single dataset. Coefficients of polynomial equations were calculated for each trait between -1 week pre-calving and week +7 postpartum using residual maximum likelihood modelling. The completed dataset was used in a multiple correlation model to determine how the best fit curves were related to each other over time. PP cows had higher concentrations of insulin-like growth factor-I and lower beta-hydroxybutyrate concentrations throughout, higher leptin concentrations pre-partum and both the peak in non-esterified fatty acids and the nadir in urea concentration occurred earlier after calving. These differences were associated with significantly lower milk production. Leptin concentrations fell at calving and were related to body condition score. Insulin was negatively correlated with yield in MP cows only. In MP cows the relationship between insulin-like growth factor-I and yield switched from negative to positive between weeks +4 and +7. Both beta-hydroxybutyrate and urea were positively related to yield in PP cows. In contrast, in MP cows beta-hydroxybutyrate was negatively correlated with yield and urea was strongly related to body condition score but not yield. These results suggest that there are differences in the control of tissue mobilization between PP and MP cows which may promote nutrient partitioning into growth as well as milk during the first lactation.

Rationale: Vascular smooth muscle cell (VSMC) proliferation causes intimal thickening in atherosclerosis andrestenosis. Previously, we demonstrated that Wnt/␤-catenin signaling upregulates VSMC proliferation in vitro.Objective: We examined this pathway in vivo and investigated the involvement of specific Wnt proteins in VSMC proliferation. Methods and Results:Left carotid arteries of TOPgal (␤-catenin signaling reporter) transgenic mice were ligated to induce intimal thickening. ␤-Catenin signaling was induced in the media and intima at 3 and 28 days after ligation, respectively, and was associated with VSMC proliferation and cyclin D1 expression. In vitro, a Wnt agonist promoted mouse VSMC proliferation, whereas Wnt inhibitory factor (WIF)-1 retarded platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation. Microarray analysis and quantitative PCR detected a significant induction of Wnt2 and Wnt4 mRNA in PDGF-BB-treated (proliferating) VSMCs compared to quiescent VSMCs. Western blotting revealed this increase was only translated into protein for Wnt4. Specific silencing RNA knockdown of Wnt4, but not Wnt2, significantly reduced VSMC proliferation. Recombinant Wnt4, but not Wnt2, significantly increased VSMC proliferation by Ϸ2-fold and silencing RNA knockdown revealed this is via Frizzled 1. Immunohistochemistry showed that increased Wnt4 protein correlated with VSMC proliferation and cyclin D1 expression (P<0.05 and P<0.001, respectively) during intimal thickening after rat carotid artery injury. Importantly, we also showed that intimal thickening and VSMC proliferation after carotid artery ligation was significantly retarded in Wnt4 ؉/؊ compared to Wnt4 ؉/؉ mice. nappropriate vascular smooth muscle cell (VSMC) activation plays a key role in pathologies that involve intimal thickening, such as atherosclerosis and restenosis after angioplasty and vein grafting. 1,2 Intimal thickening occurs as a result of augmented VSMC proliferation, in addition to increased VSMC migration, extracellular matrix synthesis and phenotypic change. 3 Recently, we and others have proposed that the Wnt/␤-catenin pathway is a novel regulator of VSMC proliferation and thereby intimal thickening. 4 -10 The Wnt family (comprised of 19 secreted, lipid-modified glycoproteins) plays a crucial role not only in the regulation of embryogenesis and development, but also in cell proliferation, differentiation, polarity, migration, and invasion (see review 11 ). Wnt proteins activate downstream signaling pathways (in a paracrine and autocrine manner) after binding to cell surface Frizzled (Fzd) receptors. 12 Abnormal Wnt signaling is associated with many human diseases, including cancer and degenerative diseases 11 ; however, the involvement of Wnt signaling in atherosclerosis and restenosis remains to be fully elucidated. ConclusionsAlthough Wnt signaling via ␤-catenin has a recognized role in controlling the proliferation of cells in human cancers, 13 its role in VSMCs has only recently been considered. We previously showed that ...

The relationships between insulin-like growth factor-I (IGF-I) and the fertility and milk yield of Holstein-Friesian dairy cows were investigated. The concentration of IGF-I in blood was measured weekly from one week before to 12 weeks after calving in 177 multiparous cows and at four times during this period in 142 primiparous cows; the concentration of IGF-I in milk was measured in 50 of the multiparous cows. The plasma concentrations of IGF-I were higher in the primiparous than in the multiparous animals. In the primiparous cows, high concentrations of IGF-I before calving were associated with longer calving to conception intervals. Conversely, in the multiparous cows low concentrations of IGF-I before and after calving were associated with a failure to conceive, despite repeated services. Multiparous cows with IGF-I concentrations of greater than 25 ng/ml in the week after calving were 11 times more likely to conceive to first service than those with lower concentrations. Concentrations of IGF-I greater than 50 ng/ml at first service increased the likelihood of conception five-fold. Cows with higher peak milk yields had lower plasma concentrations of IGF-I and took longer to return to ovarian cyclicity. The negative relationship between milk yield and return to cyclicity was stronger in the multiparous cows (P < 0.002) than in the primiparous cows (P < 0.04). The concentrations of IGF-I in milk followed a different pattern and were not associated with the changes in plasma IGF-I or fertility.

Results from 4 studies were combined (representing a total of 500 lactations) to investigate the relationships between metabolic parameters and fertility in dairy cows. Information was collected on blood metabolic traits and body condition score at 1 to 2 wk prepartum and at 2, 4, and 7 wk postpartum. Fertility traits were days to commencement of luteal activity, days to first service, days to conception, and failure to conceive. Primiparous and multiparous cows were considered separately. Initial linear regression analyses were used to determine relationships among fertility, metabolic, and endocrine traits at each time point. All metabolic and endocrine traits significantly related to fertility were included in stepwise multiple regression analyses alone (model 1), including peak milk yield and interval to commencement of luteal activity (model 2), and with the further addition of dietary group (model 3). In multiparous cows, extended calving to conception intervals were associated prepartum with greater concentrations of leptin and lesser concentrations of nonesterified fatty acids and urea, and postpartum with reduced insulin-like growth factor-I at 2 wk, greater urea at 7 wk, and greater peak milk yield. In primiparous cows, extended calving to conception intervals were associated with more body condition and more urea prepartum, elevated urea postpartum, and more body condition loss by 7 wk. In conclusion, some metabolic measurements were associated with poorer fertility outcomes. Relationships between fertility and metabolic and endocrine traits varied both according to the lactation number of the cow and with the time relative to calving.

BackgroundA reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC). Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES) of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting.MethodsPatients with advanced NSCLC due to receive first-line palliative chemotherapy were randomized to usual care with or without NMES. They were asked to undertake 30 minute sessions of NMES, ideally daily, but as a minimum, three times weekly. For NMES to be considered acceptable, it was predetermined that ≥80% of patients should achieve this minimum level of adherence. Qualitative interviews were held with a subset of patients to explore factors influencing adherence. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Quadriceps muscle strength, thigh lean mass, and physical activity level were assessed at baseline and after three cycles of chemotherapy.Results49 patients (28 male, median (IQR) age 69 (64−75) years) participated. Of 30 randomized to NMES, 18 were eligible for the primary endpoint, of whom 9 (50% [90% CI, 29 to 71]) met the minimum level of adherence. Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy. There were no serious adverse events related to NMES, nor significant differences in quadriceps muscle strength, thigh lean mass or physical activity level between groups.ConclusionsNMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.Trial RegistrationCurrent Controlled Trials ISRCTN 42944026 www.controlled-trials.com/ISRCTN42944026

The psychological adjustment of healthy siblings was investigated in relation to their attitudes and perceptions about their brother's or sister's chronic physical disorder, to their mothers' awareness of these attitudes and perceptions, and to three other maternal factors (maternal distress, maternal social support, and amount of care demanded by the physical disorder). Sixty-two well siblings and mothers of children with a range of chronic physical disorders completed standardised questionnaires. The majority of siblings did not appear to have adjustment problems, although the sample had slightly increased rates of emotional symptoms compared to the general population. Mothers rated well siblings as having more negative attitudes and perceptions about the physical disorder than reported by siblings themselves. A multiple regression analysis indicated that better sibling adjustment was associated with higher maternal awareness of their attitudes and perceptions. These findings support Varni and Wallander's (1998) model that emphasises the role of relationship and attitude variables in child adjustment to chronic physical disorder. The implications of these findings for clinical practice are discussed.

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Poor reproductive success compromises the long‐term viability of captive Asian elephant populations. A questionnaire was designed to assess the importance of reproductive behavior and husbandry factors on breeding success. This was circulated to a number of institutions, zoos, and circuses in Asia, Europe, and North America, all of which kept Asian elephants. The aims were to compare Asian elephant breeding success in different institutions, establish possible causes for any differences, and make recommendations for improving the welfare and breeding success of the animals. The results showed that breeding success in most of the zoos was notably lower and the percentages of stillbirths and infant mortality were relatively higher when compared with those of the institutions in Asia. Female elephants in zoos appeared to reach sexual maturity and reproduce earlier than those in the Asian establishments. However, zoo elephants produced fewer young per female. The different facilities and husbandry methods used are described. Recommendations are made for both short‐ and long‐term changes that could be used to modify existing practices to improve the welfare and breeding success of captive Asian elephants. Zoo Biol 17:311–332, 1998. © 1998 Wiley‐Liss, Inc.