25-Hydroxyvitamin D status, light exposure and sleep quality in UK dwelling South Asian and Caucasian postmenopausal women.

There is a lack of research into 25-hydroxyvitamin D (25(OH)D) status, light exposure and sleep patterns in South Asian populations. In addition, results of research studies are conflicting as to whether there is an association between 25(OH)D status and sleep quality. We investigated 25(OH)D status, self-reported and actigraphic sleep quality in n = 35 UK dwelling postmenopausal women (n = 13 South Asians, n = 22 Caucasians), who kept daily sleep diaries and wore wrist-worn actiwatch (AWL-L) devices for 14 days. A subset of n = 27 women (n = 11 South Asian and n = 16 Caucasian) also wore a neck-worn AWL-L device to measure their light exposure. For 25(OH)D concentration, South Asians had a median ± IQR of 43.8 ± 28.2 nmol/L, which was significantly lower than Caucasians (68.7 ± 37.4 nmol/L)(P = 0.001). Similarly, there was a higher sleep fragmentation in the South Asians (mean ± SD 36.9 ± 8.9) compared with the Caucasians (24.7 ± 7.1)(P = 0.002). Non-parametric circadian rhythm analysis of rest/activity patterns showed a higher night-time activity (L5) (22.6 ± 14.0 vs. 10.5 ± 4.4; P = 0.0008) and lower relative amplitude (0.85 ± 0.07 vs. 0.94 ± 0.02; P < 0.0001) in the South Asian compared with the Caucasian women. More South Asians (50%) met the criteria for sleep disorders (PSQI score >5) than did Caucasians (27%) (P = 0.001, Fishers Exact Test). However, there was no association between 25(OH)D concentration and any sleep parameter measured (P > 0.05) in either ethnic group. South Asians spent significantly less time in illuminance levels over 200 lx (P = 0.009) than did Caucasians. Overall, our results show that postmenopausal South Asian women have lower 25(OH)D concentration than Caucasian women. They also have higher sleep fragmentation, as well as a lower light exposure across the day. This may have detrimental implications for their general health and further research into sleep quality and light exposure in the South Asian ethnic group is warranted.

Work-family conflicts and subsequent sleep medication among women and men: a longitudinal registry linkage study.

Work and family are two key domains of life among working populations. Conflicts between paid work and family life can be detrimental to sleep and other health-related outcomes. This study examined longitudinally the influence of work-family conflicts on subsequent sleep medication. Questionnaire data were derived from the Helsinki Health Study mail surveys in 2001-2002 (2929 women, 793 men) of employees aged 40-60 years. Data concerning sleep medication were derived from the Finnish Social Insurance Institution's registers covering all prescribed medication from 1995 to 2007. Four items measured whether job responsibilities interfered with family life (work to family conflicts), and four items measured whether family responsibilities interfered with work (family to work conflicts). Cox proportional hazard models were fitted, adjusting for age, sleep medication five years before baseline, as well as various family- and work-related covariates. During a five-year follow-up, 17% of women and 10% of men had at least one purchase of prescribed sleep medication. Among women, family to work conflicts were associated with sleep medication over the following 5 years after adjustment for age and prior medication. The association remained largely unaffected after adjusting for family-related and work-related covariates. Work to family conflicts were also associated with subsequent sleep medication after adjustment for age and prior medication. The association attenuated after adjustment for work-related factors. No associations could be confirmed among men. Thus reasons for men's sleep medication likely emerge outside their work and family lives. Concerning individual items, strain-based ones showed stronger associations with sleep medication than more concrete time-based items. In conclusion, in particular family to work conflicts, but also work to family conflicts, are clear determinants of women's sleep medication.

The organ donor crisis: the missed organ donor potential from the accident and emergency departments.

The critical shortage of cadaveric donor organs for transplant purposes is a worldwide concern. The disparity between the number of cadaveric organs donated for transplant purposes and those patients awaiting transplant operations continues to widen. This article reports on the findings of an audit of deaths undertaken in 10 accident and emergency (A&E) departments in North Thames region, UK. The audit itself was borne out of informal anecdotal accounts from colleagues working in the A&E department who suggested that there was a potential pool of organ and tissue donors that were not being realized. The article discusses how those audit findings helped shape the current A&E education strategy in the North Thames region. The result has been that the North Thames region has seen a dramatic increase in the number of referrals from the A&E departments, resulting in solid organ transplantation. Although the results are very encouraging, the program is still very much in its infancy and a long way from the desired 100% referral rate. In order to maximize the number of organs from the potential donor pool, the transplant community needs to focus more attention toward donation from the A&E departments.

Investigating couples' sleep: an evaluation of actigraphic analysis techniques.

'Blip' analysis, fast wavelet transformations (FWT) and correlation analysis have all been used to actigraphically assess the impact one person is having on another's sleep, yet no review exists as to the differences between, and applicability of, these methods for investigating couples' sleep. Using actigraphy data and audio sleep diaries collected from 18 couples, this paper provides such a review. This paper constructs and assesses two novel, analytical methods: Lotjonen's sleep/wake algorithm, and the partner impact on sleep wake analysis (PISWA). Both 'blip' analysis and correlation suggest that the strongest relationship between bed partners occurs on an epoch-to-epoch basis. However, 'blips' deal strictly with onset of movement and fail to incorporate strength and duration of movement. Conversely, correlation analysis incorporates some elements of strength and duration of movement but makes identification of onset problematic. FWT offer useful 'relativistic' pattern recognition, identifying onset, strength and duration of movement, but are difficult to quantify. Although audio diary data support the potential of Lotjonen's sleep/wake algorithm to identify sleep non-movement, sleep movement, wake non-movement (or quiet wakefulness) and wake movement, the problem remains that this method also relies on visualization. Of most promise, we argue, is the PISWA, which examines 'impact' of bed partners through incorporating elements of 'blip' analysis and the sleep/wake algorithm.

Pension prospects of minority ethnic groups: inequalities by gender and ethnicity.

Minority ethnic groups have low income in later life from private pensions, partly due to shorter employment records in Britain since migration. Yet disadvantage and discrimination in the labour market, as well as differences in cultural norms concerning women's employment, may lead to persistence of ethnic variation in private pension acquisition. Little is known about the pension arrangements made by men and women in minority ethnic groups during the working life. This paper examines the extent of ethnic disadvantage in private pension scheme arrangements and analyses variation according to gender and specific ethnic group, using three years of the British Family Resources Survey, which provides information on over 97,000 adults aged 20-59, including over 5,700 from ethnic minorities. Both men and women in minority ethnic groups were less likely to have private pension coverage than their white counterparts but the extent of the difference was most marked for Pakistanis and Bangladeshis. Ethnicity interacted with gender, so that Blacks showed the least gender inequality in private pension arrangements, reflecting the relatively similar full-time employment rates of Black men and women. A minority ethnic disadvantage in private pension coverage, for both men and women, remained after taking account of age, marital and parental status, years of education, employment variables, class and income. The research suggests that minority ethnic groups - especially women - will be disproportionately dependent on means-tested benefits in later life, due to the combined effects of low private pension coverage and the policy of shifting pension provision towards the private sector.

Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation.

The patterning of skeletal muscle is thought to depend upon signals provided by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the absence of innervation. Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, is required to establish this AChR prepattern. The zone of AChR expression in muscle lacking motor axons is wider than normal, indicating that neural signals refine this muscle-autonomous prepattern. Neuronal Neuregulin-1, however, is not involved in this refinement process, nor indeed in synapse-specific AChR gene expression. Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation.

ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons.

The connections formed between sensory and motor neurons (MNs) play a critical role in the control of motor behavior. During development, the axons of proprioceptive sensory neurons project into the spinal cord and form both direct and indirect connections with MNs. Two ETS transcription factors, ER81 and PEA3, are expressed by developing proprioceptive neurons and MNs, raising the possibility that these genes are involved in the formation of sensory-motor connections. Er81 mutant mice exhibit a severe motor discoordination, yet the specification of MNs and induction of muscle spindles occurs normally. The motor defect in Er81 mutants results from a failure of group Ia proprioceptive afferents to form a discrete termination zone in the ventral spinal cord. As a consequence there is a dramatic reduction in the formation of direct connections between proprioceptive afferents and MNs. ER81 therefore controls a late step in the establishment of functional sensory-motor circuitry in the developing spinal cord.

Understanding income inequalities in health among men and women in Britain and Finland.

The aims of this study were to investigate whether the relationship between income and self-perceived health is similar for men and women in two contrasting welfare states, Britain and Finland; whether the relationship between income and health is accounted for by employment status, education, and occupational social class; and whether the association differs when using alternative ways of measuring income: gross individual and net household equivalent income. Among British and Finnish men, low household and low individual income were related to poor health, even after adjusting for employment status, education, and social class. The adjusted relationship between individual income and health was stronger for British than Finnish men. Among British and Finnish women, net household equivalent income was strongly related to health, but after adjusting for employment status, education, and social class this relationship became weaker for British women and practically disappeared for Finnish women. For British women the association between income and health differed strongly depending on the income measure used; gross individual income had almost no effect on health. These results indicate that the association between health and income has no threshold in the sense that only people in poverty have poorer health than others. In further studies of income and health, household equivalent income should be used as the principal measure of income with adjustments for employment status, and men and women should be studied separately.

Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity.

The homeobox gene Hb9, like its close relative MNR2, is expressed selectively by motor neurons (MNs) in the developing vertebrate CNS. In embryonic chick spinal cord, the ectopic expression of MNR2 or Hb9 is sufficient to trigger MN differentiation and to repress the differentiation of an adjacent population of V2 interneurons. Here, we provide genetic evidence that Hb9 has an essential role in MN differentiation. In mice lacking Hb9 function, MNs are generated on schedule and in normal numbers but transiently acquire molecular features of V2 interneurons. The aberrant specification of MN identity is associated with defects in the migration of MNs, the emergence of the subtype identities of MNs, and the projection of motor axons. These findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs.

Selective agenesis of the dorsal pancreas in mice lacking homeobox gene Hlxb9.

The initial stages of pancreatic development occur early during mammalian embryogenesis, but the genes governing this process remain largely unknown. The homeodomain protein Pdx1 is expressed in the developing pancreatic anlagen from the approximately 10-somite stage, and mutations in the gene Pdx1 prevent the development of the pancreas. The initial stages of pancreatic development, however, still occur in Pdx1-deficient mice. Hlxb9 (encoding Hb9; ref. 6) is a homeobox gene that in humans has been linked to dominant inherited sacral agenesis and we show here that Hb9 is expressed at early stages of mouse pancreatic development and later in differentiated beta-cells. Hlxb9 has an essential function in the initial stages of pancreatic development. In absence of Hlxb9 expression, the dorsal region of the gut epithelium fails to initiate a pancreatic differentiation program. In contrast, the ventral pancreatic endoderm develops but exhibits a later and more subtle perturbation in beta-cell differentiation and in islet cell organization. Thus, dorsally Hlxb9 is required for specifying the gut epithelium to a pancreatic fate and ventrally for ensuring proper endocrine cell differentiation.

Gender differences in health in later life: the new paradox?

This paper examines gender differences in health, based on data from over 14,000 men and women aged 60 and above from 3 years of the British General Household Survey, 1992-1994. There is little difference between the sexes in the reporting of self-assessed health and limiting longstanding illness, but older women are substantially more likely to experience functional impairment in mobility and personal self-care than men of the same age. These findings persist after controlling for the differential social position of men and women according to their marital status, social class, income and housing tenure. The results reveal a paradox in health reporting among older people; for a given level of disability, women are less likely to assess their health as being poor than men of the same age after accounting for structural factors. Older women's much higher level of functional impairment co-exists with a lack of gender difference in self-assessed health.

Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression.

Motor function depends on the formation of selective connections between sensory and motor neurons and their muscle targets. The molecular basis of the specificity inherent in this sensory-motor circuit remains unclear. We show that motor neuron pools and subsets of muscle sensory afferents can be defined by the expression of ETS genes, notably PEA3 and ER81. There is a matching in PEA3 and ER81 expression by functionally interconnected sensory and motor neurons. ETS gene expression by motor and sensory neurons fails to occur after limb ablation, suggesting that their expression is coordinated by signals from the periphery. ETS genes may therefore participate in the development of selective sensory-motor circuits in the spinal cord.

Use of health services by children and young people according to ethnicity and social class: secondary analysis of a national survey.

OBJECTIVE: To assess whether equity is achieved in use of general practitioner, outpatient, and inpatient services by children and young people according to their ethnic group and socioeconomic background. DESIGN: Secondary analysis of the British general household survey, 1991-94. SUBJECTS: 20 473 children and young people aged between 0 and 19 years. MAIN OUTCOME MEASURES: Consultations with a general practitioner within a two week period, outpatient attendances within a three month period, and inpatient stays during the past year. RESULTS: There were no significant class differences in the use of health services by children and young people, and there was little evidence of variation in use of health services according to housing tenure and parental work status. South Asian children and young people used general practitioner services more than any other ethnic group after controlling for socioeconomic background and perceived health status, but the use of hospital outpatient and inpatient services was significantly lower for children and young people from all minority ethnic groups compared with the white population. CONCLUSIONS: Our results differ from previous studies, which have reported significant class differences in use of health services for other age groups. We found no evidence that children and young people's use of health services varied according to their socioeconomic status, suggesting that equity has been achieved. A child or young person's ethnic origin, however, was clearly associated with use of general practitioner and hospital services, which could imply that children and young people from minority ethnic groups receive a poorer quality of health care than other children and young people.

Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase.

Cell division, cell motility and the formation and maintenance of specialized structures in differentiated cells depend directly on the regulated dynamics of the actin cytoskeleton. To understand the mechanisms of these basic cellular processes, the signalling pathways that link external signals to the regulation of the actin cytoskeleton need to be characterized. Here we identify a pathway for the regulation of cofilin, a ubiquitous actin-binding protein that is essential for effective depolymerization of actin filaments. LIM-kinase 1, also known as KIZ, is a protein kinase with two amino-terminal LIM motifs that induces stabilization of F-actin structures in transfected cells. Dominant-negative LIM-kinasel inhibits the accumulation of the F-actin. Phosphorylation experiments in vivo and in vitro provide evidence that cofilin is a physiological substrate of LIM-kinase 1. Phosphorylation by LIM-kinase 1 inactivates cofilin, leading to accumulation of actin filaments. Constitutively active Rac augmented cofilin phosphorylation and LIM-kinase 1 autophosphorylation whereas phorbol ester inhibited these processes. Our results define a mechanism for the regulation of cofilin and hence of actin dynamics in vivo. By modulating the stability of actin cytoskeletal structures, this pathway should play a central role in regulating cell motility and morphogenesis.

Health-related social mobility: a comparison of currently employed men and women in Britain and Finland.

Selective health-related social mobility has been suggested as one possible explanation for health inequalities. The aim of this paper is to examine the size and significance of the contribution which health-related social mobility makes to social class differences in health. We do this by examining the association between intergenerational social mobility and health among currently employed men and women in Britain and Finland. We used comparable nationally representative interview surveys from Britain and Finland. The British data is derived from the General Household Survey for 1988 and 1989, and the Finnish data from the 1986 Survey on Living Conditions. Health measures included limiting long-standing illness and self-assessed health as below good. Social mobility was measured comparing the respondent's class of origin (father's occupation) with his/her class of destination (own current occupation). Social structural changes and related social mobility have been more dramatic in Finland than in Britain during the last few decades. Downward mobility has been relatively rare, and mobility has taken place predominantly upwards. In Finland downward mobility from upper non-manual to manual worker was associated with a somewhat higher risk of limiting long-standing illness than expected among men as well as women. However, there was no statistically significant interaction effect on health between the respondent's father's occupational class and his/her own current class. In Britain, neither self-assessed health nor limiting long-standing illness were related to social mobility. Some weak evidence for health-related downward social mobility was found for currently employed Finnish men and women, but not for their British counterparts. Moreover, the evidence is weaker for self-assessed health than for limiting long-standing illness. Where social mobility may have been health-related, it concerns very rare and small groups; therefore health inequalities among the currently employed cannot be explained by intergenerational health-related social mobility.

Comparing inequalities in women's and men's health: Britain in the 1990s.

Data on over 20,000 women and men aged 20-59 are analysed from the British General Household Survey for 1991 and 1992, showing the importance of separately analysing educational qualifications, occupational class and employment status for both women and men. Own occupational class and employment status are the key structural factors associated with limiting long-standing illness, but educational qualifications are particularly good predictors of women's self-assessed health. Class inequalities in health are less pronounced among women who are not in paid work. Women's limiting long-standing illness relates solely to their own labour market characteristics, whereas self-assessed health relates to wider aspects of women's everyday lives, including their household material conditions, and for married women, their partner's occupational class and employment status. Men's unemployment has adverse consequences for the health of their wives, which occurs through the mechanism of the family living in disadvantaged material circumstances. Women's labour market position and role in the family have undergone substantial changes since the 1970s. Approaches to measuring inequalities in women's health need to reflect changes in women's employment participation and changes in marital status and living arrangements.

MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure.

MLP is a LIM-only protein of terminally differentiated striated muscle cells, where it accumulates at actin-based structures involved in cytoarchitecture organization. To assess its role in muscle differentiation, we disrupted the MLP gene in mice. MLP (-/-) mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Ultrastructural analysis revealed dramatic disruption of cardiomyocyte cytoarchitecture. At birth, these hearts were not hypertrophic, but already abnormally soft, with cell-autonomous and MLP-sensitive alterations in cytoarchitecture. Thus, MLP promotes proper cardiomyocyte cytoarchitecture, whose perturbation can lead to dilated cardiomyopathy. In vivo analysis revealed that MLP-deficient mice reproduce the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans, providing the first model for this condition in a genetically manipulatable organism.

Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis.

The characteristic shapes and positions of each individual body muscle are established during the process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary myotubes are arranged in small parallel bundles, each myotube spanning the forming muscles from end to end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle morphogenesis. We have cloned muscle ankyrin repeat protein (MARP) as a gene induced in adult rat skeletal muscle by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and D.H. Presky. 1995. J. Biol. Chem. 270:10236-10245) and is identical to rat cardiac ankyrin repeat protein. (Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey, and K.R. Chien. 1997. Development. 124:793-804). In denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also expressed in large blood vessels and in cardiac muscle, where it was further induced by cardiac hypertrophy. During embryonic development, MARP was expressed in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript exclusively accumulates at the end regions of primary myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in adjacent prospective tendon mesenchyme, suggesting that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both MARP mRNA and protein are controlled by rapid degradation mechanisms characteristic of regulatory early response genes. The results establish the existence of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon mesenchyme to forming muscle and from activated muscle interstitial cells to denervated muscle fibers.