Impact of Parenteral Nutrition Versus Fasting on Hepatic Bile Acid Production and Transport in a Rabbit Model of Prolonged Critical Illness

Cholestatic liver dysfunction frequently occurs during critical illness. Administration of parenteral nutrition (PN) is thought to aggravate this. Underlying mechanisms are not clear.status: publishe

FGF19 Regulates Cell Proliferation, Glucose and Bile Acid Metabolism via FGFR4-Dependent and Independent Pathways

Fibroblast growth factor 19 (FGF19) is a hormone-like protein that regulates carbohydrate, lipid and bile acid metabolism. At supra-physiological doses, FGF19 also increases hepatocyte proliferation and induces hepatocellular carcinogenesis in mice. Much of FGF19 activity is attributed to the activation of the liver enriched FGF Receptor 4 (FGFR4), although FGF19 can activate other FGFRs in vitro in the presence of the coreceptor βKlotho (KLB). In this report, we investigate the role of FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v) which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation

What do older people do when sitting and why? Implications for decreasing sedentary behaviour

Background and Objectives: Sitting less can reduce older adults’ risk of ill health and disability. Effective sedentary behavior interventions require greater understanding of what older adults do when sitting (and not sitting), and why. This study compares the types, context, and role of sitting activities in the daily lives of older men and women who sit more or less than average. Research Design and Methods: Semistructured interviews with 44 older men and women of different ages, socioeconomic status, and objectively measured sedentary behavior were analyzed using social practice theory to explore the multifactorial, inter-relational influences on their sedentary behavior. Thematic frameworks facilitated between-group comparisons. Results: Older adults described many different leisure time, household, transport, and occupational sitting and non-sitting activities. Leisure-time sitting in the home (e.g., watching TV) was most common, but many non-sitting activities, including “pottering” doing household chores, also took place at home. Other people and access to leisure facilities were associated with lower sedentary behavior. The distinction between being busy/not busy was more important to most participants than sitting/not sitting, and informed their judgments about high-value “purposeful” (social, cognitively active, restorative) sitting and low-value “passive” sitting. Declining physical function contributed to temporal sitting patterns that did not vary much from day-to-day. Discussion and Implications: Sitting is associated with cognitive, social, and/or restorative benefits, embedded within older adults’ daily routines, and therefore difficult to change. Useful strategies include supporting older adults to engage with other people and local facilities outside the home, and break up periods of passive sitting at home

Factors influencing quality of life following lower limb amputation for peripheral arterial occlusive disease: a systematic review of the literature

Background: The majority of lower limb amputations are undertaken in people with peripheral arterial occlusive disease,\ud and approximately 50% have diabetes. Quality of life is an important outcome in lower limb amputations; little is known\ud about what influences it, and therefore how to improve it.\ud Objectives: The aim of this systematic review was to identify the factors that influence quality of life after lower limb\ud amputation for peripheral arterial occlusive disease.\ud Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science and Cochrane databases were searched to identify\ud articles that quantitatively measured quality of life in those with a lower limb amputation for peripheral arterial occlusive\ud disease. Articles were quality assessed by two assessors, evidence tables summarised each article and a narrative\ud synthesis was performed.\ud Study design: Systematic review.\ud Results: Twelve articles were included. Study designs and outcome measures used varied. Quality assessment scores\ud ranged from 36% to 92%. The ability to walk successfully with a prosthesis had the greatest positive impact on quality\ud of life. A trans-femoral amputation was negatively associated with quality of life due to increased difficulty in walking\ud with a prosthesis. Other factors such as older age, being male, longer time since amputation, level of social support and\ud presence of diabetes also negatively affected quality of life.\ud Conclusion: Being able to walk with a prosthesis is of primary importance to improve quality of life for people with lower\ud limb amputation due to peripheral arterial occlusive disease. To further understand and improve the quality of life of this\ud population, there is a need for more prospective longitudinal studies, with a standardised outcome measure

What aspects of periods are most bothersome for women reporting heavy menstrual bleeding? Community survey and qualitative study

Background: Heavy menstrual bleeding is a common symptom amongst women of reproductive age, yet questions remain about why some women experience this as a problem while others do not. We investigated the concerns of women who reported heavy menstrual bleeding on questionnaire. Methods: A cross-sectional postal survey and qualitative interviews were carried out amongst a community-based sample of women in Lothian, Scotland. 906 women aged 25 to 44 reported heavy or very heavy periods in response to a postal survey of 2833 women registered with 19 general practices. Amongst those who had reported heavy menstrual bleeding, analysis was carried out of responses to the free text questionnaire item, "What bothers you most about your periods?" In addition, 32 of these women participated in qualitative interviews and their accounts were analysed to explore how menstrual symptoms and 'problems' with periods were experienced. Results: Even amongst this subgroup of women, selected on the basis of having reported their periods as heavy in the survey, pain was the aspect of their periods that 'most bothered' them, followed by heaviness, mood changes or tiredness, and irregularity or other issues of timing. Interviewees' accounts similarly suggested that a range of menstrual symptoms were problematic and some women did not disentangle which was worst. Judgements of periods as a problem were based on the impact of menstrual symptoms on daily life and this was contingent on social circumstances such as type of paid work and other responsibilities. Although women spoke readily of whether their periods were a problem, there was less clarity in accounts of whether or not menstrual loss was 'heavy'; women said they made judgements based on what was normal for them, degree of difficulty in containing blood loss and pattern of loss. Conclusion: Women with heavy periods are bothered by a range of menstrual symptoms and their impact on everyday life. Clinical emphasis should be on clarifying the presenting problem and providing help and advice for this, as well as on excluding serious disease. Sometimes simple approaches, such as help with analgesia, may be all that is required

Shared decision-making – Rhetoric and reality: Women’s experiences and perceptions of adjuvant treatment decision-making for breast cancer

This interview-based study uses phenomenology as a theoretical framework and thematic analysis to challenge existing explanatory frameworks of shared decision-making, in an exploration of women’s experiences and perceptions of shared decision-making for adjuvant treatment in breast cancer. Three themes emerged are as follows: (1) women’s desire to participate in shared decision-making, (2) the degree to which shared decision-making is perceived to be shared and (3) to what extent are women empowered within shared decision-making. Studying breast cancer patients’ subjective experiences of adjuvant treatment decision-making provides a broader perspective on patient participatory role preferences and doctor–patient power dynamics within shared decision-making for breast cancer

Characteristics of a protocol to collect objective physical activity/sedentary behaviour data in a large study : seniors USP (understanding sedentary patterns)

The Seniors USP study measured sedentary behaviour (activPAL3, 9 day wear) in older adults. The measurement protocol had three key characteristics: enabling 24-hour wear (monitor location, waterproofing); minimising data loss (reducing monitor failure, staff training, communication); and quality assurance (removal by researcher, confidence about wear). Two monitors were not returned; 91% (n=700) of returned monitors had 7 valid days of data. Sources of data loss included monitor failure (n=11), exclusion after quality assurance (n=5), early removal for skin irritation (n=8) or procedural errors (n=10). Objective measurement of physical activity and sedentary behaviour in large studies requires decisional trade-offs between data quantity (collecting representative data) and utility (derived outcomes that reflect actual behaviour). Keywords: methodology; accelerometer; adherence; data loss; activPAL; postur

Development of the Epilepsy Risk Awareness scale (ERA scale) for people with epilepsy

Purpose: Quality of life in people with epilepsy depends on balancing protection from risks and avoiding unnecessary restrictions. The Epilepsy Risk Awareness Checklist (ERAC) was developed to summarise an individual’s safety, health care and quality of life and to facilitate communication between professionals. Although effective, the existing Checklist required quantification and shortening to increase its utility, particularly as a longitudinal tool for measuring and communicating changes over time. Methods: 5 clinical experts, 3 people with epilepsy and 5 carers assessed the importance of each item on the ERAC questionnaire in a two-round Delphi survey. The refined Epilepsy Risk Awareness scale (ERA scale) was piloted in 30 patients to obtain an overall and sub-scale score for personal safety, health care, and quality of life domains, and was compared with the validated Seizure Severity Scale and Epilepsy Self-Management Scale. Results: ERAC was shortened from 69 to 48 items to take 15–20 min for completion. Pilot results showed good internal consistency for the overall ERA scale, for the Personal Safety and Health Care subscales, but less for the Quality of Life subscale. There was strong association between ERA scale and the Epilepsy Self- Management Scale, but little relationship with Seizure Severity Scale scores, which focus on individual seizures. User ratings were high. Conclusions: The ERA scale has been shortened and quantified to provide an objective measure of the risks and safety profile in people with epilepsy. The scale will be further tested for intra-rater variability and utility

Aged PROP1 Deficient Dwarf Mice Maintain ACTH Production

Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD) that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH) deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1null (Prop1-/-) and the Ames dwarf (Prop1df/df) mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism