Expression of glucocorticoid receptor, mineralocorticoid receptor, and 11beta-hydroxysteroid dehydrogenase 1 and 2 in the fetal and postnatal ovine hippocampus: ontogeny and effects of prenatal glucocorticoid exposure

To determine the expression of glucocorticoid metabolizing and action genes in the hippocampus of fetal, neonatal, and adult sheep. Pregnant ewes (or their fetuses) received intramuscular injections of saline or betamethasone (BETA, 0-5 mg/kg) at 104, 111, 118, and/or 125 days of gestation (dG). Hippocampal tissue was collected prior to (75, 84, and 101 dG), during (109 and 116 dG), or after (121, 132, and 146 dG; 6 and 12 postnatal weeks; 3.5 years of age) saline or BETA injections. Hippocampal glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11beta-hydroxysteroid dehydrogenase (11betaHSD)1 and 11betaHSD2 mRNA levels were determined using qRT-PCR. Control animals late in gestation demonstrated a decrease in mRNA encoding GR and 11betaHSD1, whereas 11betaHSD2 was undetectable, consistent with a damping of the negative feedback influence of circulating or locally produced cortisol on the hypothalamic-pituitary-adrenal (HPA) axis. BETA-administration had transient effects on fetal GR and MR, and early in postnatal life (12 weeks of age) 11betaHSD1 mRNA was increased. Hippocampal MR mRNA was elevated in adult offspring exposed to either one or four doses of maternal BETA (P<0.001). Four courses of maternal BETA increased 11betaHSD2 (P<0.05) but not 11betaHSD1 mRNA levels. Late in gestation a reduction in hippocampal GR and 11betaHSD1 mRNA suggests lessening of glucocorticoid negative feedback, facilitating increased preterm HPA activity and parturition. Adult offspring of BETA-treated mothers demonstrated increased MR and 11betaHSD2 mRNA, therefore it appears that exposure of fetus to high levels of synthetic glucocorticoids may have long-lasting effects on the hippocampal expression of HPA-related genes into adulthood.     

Loss of agouti-related peptide does not significantly impact the phenotype of murine POMC deficiency

The hypothalamic melanocortin system is unique among neuropeptide systems controlling energy homeostasis, in that both anorexigenic proopiomelanocortin (POMC)-derived and orexigenic Agouti related-peptide (AgRP)-derived ligands act at the same receptors, namely melanocortin 3 and 4 receptors (MC3/4R). AgRP clearly acts as a competitive antagonist at MC3R and MC4R but may also have an inverse agonist action at these receptors. The physiological relevance of this remains uncertain. We generated a mouse lacking both POMC and AgRP [double knockout (DKO) mouse]. Phenotyping was performed in the absence and presence of glucocorticoids, and the response to central peptide administration was studied. The phenotype of DKO mice is indistinguishable from that of mice lacking Pomc alone, with both exhibiting highly similar degrees of hyperphagia and increased body length, fat, and lean mass compared with wild-type controls. After a 24-h fast, there was no difference in the refeeding response between Pomc(-/-) and DKO mice. Similarly, corticosterone supplementation caused an equivalent increase in food intake and body weight in both genotypes. Although the central administration of [Nle?, d-Phe?]-α-MSH to DKO mice caused a decrease in food intake and an increase in brown adipose tissue Ucp1 expression, both of which could be antagonized with the coadministration of AgRP, there was no effect of AgRP alone. These data suggest AgRP acts predominantly as a melanocortin antagonist. If AgRP has significant melanocortin-independent actions, these are of insufficient magnitude in vivo to impact any of the detailed phenotypes we have measured under a wide variety of conditions.     

Standards of care in day hospitals and day centres: a comparison of services for older people with dementia

BACKGROUND: Current policy in England emphasises the importance of caring for highly dependent older people for as long as possible at home. It is therefore crucial that day care services are effective and widely available. AIM: To compare the type and standard of care provided for older people with dementia in day centre and day hospital settings. METHODS: A cross-sectional postal survey design was employed. Representatives from three-quarters of identified specialist day care services for older people with dementia in the North West of England provided information on a range of indicators including: basic structural features; delivery of care; service content; and quality measures. RESULTS: Day hospitals tended to have more day care places and a greater number of attendees, but lower occupancy rates than day centres. Day hospitals reported higher standards of care in relation to systematic assessment and care planning, promotion of rehabilitation, carer involvement and individualised provision of care. They were also more likely to employ building design features to encourage independence and choice for people with dementia. A higher proportion of day centres provided services exclusively to older people with dementia and a greater proportion of staff in day centres had undergone specific training in caring for people with dementia. Day centres were also more likely to have effective transport arrangements in place. CONCLUSION: The standards developed for the study were sufficiently reliable to allow for an acceptable estimate of quality. Day centres and day hospitals appeared to perform two distinct, but complementary functions. These results provide key material for shaping the provision of day care for older people with dementia, especially given the absence of national standards in this area.     

The needs of older people with dementia in residential care

BACKGROUND: People with dementia often move into care homes as their needs become too complex or expensive for them to remain in their own homes. Little is known about how well their needs are met within care homes. METHOD: The aim of this study was to identify the unmet needs of people with dementia in care and the characteristics associated with high levels of needs. Two hundred and thirty-eight people with dementia were recruited from residential care homes nationally. Needs were identified using the Camberwell Assessment of Needs for the Elderly (CANE). RESULTS: Residents with dementia had a mean of 4.4 (SD 2.6) unmet and 12.1 (SD 2.6) met needs. Environmental and physical health needs were usually met. However, sensory or physical disability (including mobility problems and incontinence) needs, mental health needs, and social needs, such as company and daytime activities, were often unmet. Unmet needs were associated with psychological problems, such as anxiety and depression, but not with severity of dementia or level of dependency. CONCLUSION: Mental health services and residential home staff need to be aware that many needs remain unmet and much can be done to improve the quality of life of the residents with dementia.     

An intervention study to reduce adverse pregnancy outcomes as a result of syphilis in Mozambique

OBJECTIVES: To create and evaluate an alternative screening approach among pregnant women in order to reduce adverse pregnancy outcome as a result of syphilis in Mozambique. METHODS: Four suburban antenatal clinics, two "control" and two "intervention" clinics, were compared regarding syphilis screening and treatment. Pregnant women with positive rapid plasma reagin (RPR) test (n = 929) were enrolled, 453 in the intervention and 476 in the control clinics. In control clinics the normal routine regarding syphilis screening was followed for 383 women remaining for follow up. In intervention clinics nurse midwives were trained to perform the RPR test. RPR seropositive cases were immediately treated on site by the nurse midwives and the partners were invited to come any afternoon for treatment. In the third trimester (around 30 weeks) a new RPR test was performed and all women with positive RPR test results were again treated and the partners were invited to come for treatment. RESULTS: At delivery, the drop out rate was 15.7% in the intervention and 20.1% in the control group. The perinatal mortality was significantly higher in the control group than in the intervention group, 3.4% v 1.3% (p = 0.030). At delivery the intervention group had significantly more negative RPR results--40.9% v 24.2% (p = 0.000). CONCLUSION: More active training of nurse midwives in antenatal care to perform on site RPR tests, to give syphilis treatment, and to notify partners results in improved perinatal outcome and more seronegative parturient women.     

减病原体ABO通用血浆的输注指证和成本效益

ABO不相容输注错误仍是主要危险之一,来自英国输血严重风险(SHOT)的血液预警计划累积的资料显示,超过70%的严重危险来自错误血液的输注.ABO通用血液的供应将简化后勤、降低安全保障成本和消除由ABO不相容引起的输血错误.