Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

Beliefs about inevitable decline among home-living older adults at risk of malnutrition: a qualitative study.

BACKGROUND: Approximately 14% of free-living adults aged ≥65 years are at risk of malnutrition. Malnutrition screen and treat interventions in primary care are few, show mixed results, and the advice given is not always accepted and followed. We need to better understand the experiences and contexts of older adults when aiming to develop interventions that are engaging, optimally persuasive and relevant. METHODS: Using the Person-based Approach, we carried out 23 semi-structured interviews with purposively selected adults ≥65 years with chronic health or social conditions associated with malnutrition risk. Thematic analysis informed the development of key principles to guide planned intervention development. RESULTS: We found that individuals' beliefs about an inevitable decline in appetite and eating in older age compound the many and varied physical and physiological barriers that they experience. Also, we found that expectations of decline in appetite and physical ability may encourage resignation, reduce self-efficacy to overcome barriers, and reduce motivation to address weight loss and/or recognise it as an issue that needs to be addressed. Fear of loss of independence may also reduce the likelihood of asking general practitioners for advice. CONCLUSIONS: The key findings identified include a sense of resignation, multiple different barriers to eating and a need for independence, each underpinned by the expectation of a decline in older adulthood. Interventions need to address misperceptions about the inevitability of decline, highlight how and why diet recommendations are somewhat different from recommendations for the general population, and suggest easy ways to increase food intake that address common barriers.

Education Coupled With In-Situ High Fidelity Simulation Improves Medical-Surgical RN Code Blue Comfort Levels.

Pediatric, cardiopulmonary arrest is a rare event outside intensive care units in children's hospitals. Medical-surgical RNs rarely are involved in code situations and are often uncomfortable in performing necessary tasks. We implemented a multi-disciplinary educational plan, coupled with in-situ high-fidelity simulation, aimed at improving medical-surgical, RN comfort levels during codes. 260 medical surgical RNs on 10 separate hospital units parficipated. Pre and post intervention surveys were collected and compared. Results revealed a significant increase in the proportion of RNs responding "very comfortable" in all categories. Education, coupled with in-situ high-fidelity simulation, is an effective tool to increase RN comfortable levels during codes.

Taurolidine locks significantly reduce the incidence of catheter-related blood stream infections in high-risk patients on home parenteral nutrition.

Emerging evidence suggests taurolidine reduces the risk of repeated episodes of catheter related blood stream infections (CRBSI) in a subgroup of patients receiving home parenteral nutrition (HPN). We defined 3 indications where taurolidine could be considered and retrospectively analysed data from patients who were treated over a 10 year period to examine the validity of these criteria. Twenty-two patients were identified from a total HPN population of 81, representing 33.2 years of experience. The overall CRBSI rate pre- and post-taurolidine usage was reduced from 5.71 to 0.99 infections per 1000 patient parenteral nutrition days (P-value <0.0001), with reductions identified in each smaller subgroup, confirming previous reports of a significant reduction in infections when taurolidine is used as secondary prophylaxis and providing initial data suggesting the benefit of its use as primary prophylaxis.

Oedema is associated with clinical outcome following emergency abdominal surgery.

INTRODUCTION: Oedema is observed frequently following surgery and may be associated with worse outcomes. To date, no study has investigated the role of oedema in the emergency surgical patient. This study assesses the incidence of oedema following emergency abdominal surgery and the value of early postoperative oedema measurement in predicting clinical outcome. METHODS: A prospective cohort study of patients undergoing emergency abdominal surgery at a university unit over a two-month period was undertaken. Nutritional and clinical outcome data were collected and oedema was measured in the early postoperative period. Predictors of oedema and outcomes associated with postoperative oedema were identified through univariate and multivariate analysis. RESULTS: Overall, 55 patients (median age: 66 years) were included in the study. Postoperative morbidity included ileus (n=22) and sepsis (n=6) with 12 deaths at follow-up. Postoperative oedema was present in 19 patients and was associated with prolonged perioperative fasting (107 vs 30 hours, p=0.009) but not with body mass index (24 kg/m(2) vs 27 kg/m(2), p=0.169) or preadmission weight loss (5% vs 3%, p=0.923). On multivariate analysis, oedema was independently associated with gastrointestinal recovery (B=6.91, p=0.038), artificial nutritional support requirement (odds ratio: 6.91, p=0.037) and overall survival (χ(2) =13.1, df=1, p=0.001). CONCLUSIONS: Generalised oedema is common after emergency abdominal surgery and appears to independently predict gastrointestinal recovery, the need for artificial nutritional support and survival. Oedema is not associated with commonly applied markers of nutritional status such as body mass index or recent weight loss. Measurement of oedema offers utility in identifying those at risk of poor clinical outcome or those requiring artificial nutritional support following emergency abdominal surgery.

The 'not so short-bowel syndrome': potential health problems in patients with an ileostomy.

AIM: The study aimed to determine whether an ileostomy compromises nutritional, hydration and electrolyte status and bone mineral density. METHOD: Body weight, body mass index (BMI) and fat and lean body mass (LBM) were measured in 60 patients with an ileostomy [14 small-bowel resection (SBR); 46 non-small-bowel resection (NSBR)] and in 60 age- and sex-matched normal controls. Measurement of plasma sodium, potassium, calcium, magnesium, urea and creatinine and 24-h urinary output of water, Na, K, Ca and Mg was made in 45 NSBR and 14 SBR ileostomists and in all the controls. Forty-six NSBR and 13 SBR ileostomists had bone mineral density (BMD) measurements of lumbar spine (LS) and femoral neck (FN). RESULTS: The body weight of ileostomists was less than controls [median 67.8 (36.4-115.1) vs 77.7 (48.0-103.3) kg; P < 0.05]. BMI was also less [25.0 (14.3-43.0) vs 27.3 (20.2-32.2) kg/m(2) ; P < 0.05] with a lower LBM [47.8 (19.3-73.0) vs 52.9 (34.0-73.8) kg; P < 0.05]. The 24-h urinary output of the ileostomists was lower than for controls [1380 (430-4690) vs 2000 (840-4440) ml/24 h; P < 0.05] suggesting some degree of dehydration. In 62.7% of ileostomists 24-h urinary Na excretion was < 100 mmol/day vs 16.7% of controls, and ileostomists with lower urinary Na were more likely than ileostomists with normal Na excretion to have a low BMI [23.9 (14.3-33.0) vs 28.4 (16.6-43.0) kg/m(2) ; P < 0.001] and LBM [44.1 (19.3-73.0) vs 59.5 (36.6-67.9) kg; P < 0.001]. The respective 24-h output of Ca was [2.2 (0-6.1) vs 4.7 (0-13) mmol; P < 0.001] and Mg was [2.0 (0-13.7) vs 3.9 (1.2-5.4) mmol; P < 0.001], and BMD Z-score LS was -0.15 (-2.0 to 5.2) vs 0.3 (-2.5 to 2.1), Z-score FN -0.5 (-1.9 to 3.1) vs 0.2 (-1.2 to 1.4), both P < 0.05. CONCLUSION: Patients with an ileostomy tend to have low body weight, BMI, LBM and BMD. They also tend to have low urine volumes, and some are depleted of Na, Ca and Mg. Abnormalities are greater in those with a lower urinary Na and measuring this will identify ileostomists at risk of Na depletion who will be benefitted by Na supplements.

Complications of emergency refeeding in anorexia nervosa: case series and review.

The refeeding syndrome is common among patients with anorexia nervosa. It may be lethal and has many manifestations. We report a case series of 14 anorexic patients admitted for feeding to a single British centre. There was a high prevalence of the refeeding syndrome, with three cases requiring higher dependency unit support and one death. We present a review of the refeeding syndrome in anorectics and highlight our impression that infection among such patients may be serious and under-recognised.

Improving peri-operative fluid management in a large teaching hospital: pragmatic studies on the effects of changing practice.

Concerns about the over-prescription of peri-operative fluids, particularly normal saline, culminated in the recent publication of UK national guidelines on fluid prescription during and after surgery. A working group comprising members of the nutrition support team, surgeons, anaesthetists and pharmacists therefore sought to reduce the overall levels of fluid prescription and to limit normal saline usage in our large Teaching Hospital by producing written local fluid prescribing guidelines and holding a series of fluid prescription education sessions for consultants and junior staff. Ideally, the success of such measures would have been determined by studies on fluid balance, body weight and/or measured body water in large numbers of individual patients in a large cluster-randomised controlled trial. However, this would have proved logistically difficult and very costly especially as it is notoriously difficult to rely on the accuracy of daily fluid balance charts in large numbers of patients on busy post-operative surgical wards. We therefore undertook a pragmatic study, comparing historical data on fluid type/volume prescribed (from both individual and ward level pharmacy records), oedema status and clinical outcomes from 2002 with two prospective audits of similar data carried out during 2008 and 2009. Our data showed that in the comparable, elective surgical patients within each audit, there was a decline in total intravenous fluids prescribed over the first 5 post-operative days from 21·1 litres per patient in 2002 to 14·2 litres per patient in 2009 (P<0·05), while pharmacy records showed that the proportion of 0·9% saline supplied declined from 60% to 35% of all fluids supplied to the surgical wards involved, with a concomitant increase in the use of 4%/0·18% dextrose-saline and Hartmann's solution. Alongside these changes in fluid prescribing, the number of patients with clinically apparent oedema declined from 53% in 2002 to 36% in 2009; gut function returned more quickly (6 d in 2002 v. 4 d in 2009, P<0·05) and the length of stay improved from 13 d in 2002 to 10 d in 2009, P<0·05). Although we accept that other factors might have contributed to the observed changes in these clinical parameters, we believe that the measures to reduce fluid and saline administration were the major contributors to these improved clinical outcomes.

Notch signaling is not essential in sonic hedgehog-activated medulloblastoma.

Dysregulated signal transduction through the notch pathway has been noted in human and mouse medulloblastoma studies. Gamma secretase inhibitors (GSIs) impair notch signaling by preventing the cleavage of transmembrane notch proteins into their active intracellular domain fragments. Previous studies have shown that GSI treatment caused apoptosis and impaired medulloblastoma cell engraftment in xenograft systems. In this study, we used in vivo genetic and pharmacologic approaches to quantify the contribution of notch signaling to sonic hedgehog (shh)-activated mouse medulloblastoma models. In contrast to prior in vitro studies, pharmacologic inhibition of notch pathways did not reduce the efficiency of medulloblastoma xenotransplantation nor did systemic therapy impact tumor size, proliferation, or apoptosis in genetically engineered mouse medulloblastoma models. The incidence and pathology of medulloblastomas driven by the SmoA1 transgene was unchanged by the bi-allelic absence of Notch1, Notch2, or Hes5 genes. These data show that notch signaling is not essential for the initiation, engraftment, or maintenance of sonic hedgehog pathway-driven medulloblastomas.

Impact of oedema on recovery after major abdominal surgery and potential value of multifrequency bioimpedance measurements.

BACKGROUND: The consequences of generalized oedema following major abdominal surgery are under-recognized, and its causes are poorly understood. METHODS: Thirty-eight patients (21 men and 17 women) were observed for the occurrence of oedema after major abdominal surgery. Oedema formation was related to fluid balance, changes in whole-body bioimpedance (Z) measured at four frequencies (5, 50, 100 and 200 kHz), and clinical outcome. RESULTS: The 20 patients who developed oedema were older than those who did not (mean(s.d.) 73(9) versus 63(14) years; P = 0.007). Fluid intake over the first 5 days after surgery was similar in both groups, but those with oedema excreted less total fluid (16.9(2.4) versus 19.7(3.5) litres; P = 0.022). Oedema was associated with a delay in tolerating solid food (P = 0.001) and opening bowels (P = 0.020), a prolonged hospital stay (median 17 (range 8-59) versus 9 (range 4-27) days; P = 0.001) and more postoperative complications (13 of 20 versus four of 18 patients; P = 0.011). The preoperative ratio of whole-body impedance at 200 kHz to that at 5 kHz was higher in those who subsequently developed oedema (0.81(0.03) versus 0.78(0.02); P = 0.015). CONCLUSION: The development of oedema after major abdominal surgery is associated with increased morbidity. Age and reduced ability to excrete administered fluid load are significant aetiological factors and bioimpedance analysis can potentially identify patients at risk.

Risk factors for interstage death after the Norwood procedure.

Operative survival after the Norwood procedure has significantly improved during the past 10 years. However, there remains attrition among Norwood survivors before reaching planned second-stage palliation. The purpose of this study was to evaluate potential risk factors for interstage mortality among Norwood survivors. All patients undergoing the Norwood procedure at the Medical University of South Carolina from January 1996 through January 2001 were retrospectively reviewed. Patient and procedural variables were examined as potential risk factors for interstage mortality. Among 50 Norwood survivors, 8 (16%) died prior to second-stage palliation. The mean age at death was 102 +/- 72 days (median, 61; range, 35-208). By multivariate analysis, the presence of an arrhythmia in the postoperative period (p = 0.02) and decreased ventricular function at hospital discharge (p = 0.05) were identified as risk factors for interstage mortality. There remains a significant risk for interstage mortality among Norwood survivors. Patients with postoperative arrhythmias and/or decreased ventricular function at discharge are at increased risk for interstage death after Norwood procedure. More frequent follow-up and aggressive medical management of arrhythmia or decreased function may be warranted for these high-risk patients.

Early hormonal therapy stabilizes hemodynamics during donor procurement.

BACKGROUND: Hemodynamic instability has been implicated in the loss of otherwise transplantable organs. We examined the hypothesis that administration of hormonal therapy early during donor management would stabilize hemodynamics and increase the number of organs procured. METHODS: We retrospectively analyzed 133 consecutive donor records from a single organ procurement organization. Controls (C) received no early hormonal therapy. A steroid group (S) received methylprednisolone only and a combination hormonal therapy group (CH) received thyroxine, methylprednisolone, dextrose, and insulin at the start of donor management (t(0h)). Adrenergic support was adjusted to maintain mean arterial blood pressure (MAP) at > or =60 mm Hg. Doses of adrenergic agents were assessed at t(0h), 4 hours (t(4h)), and just prior to procurement (t(proc)). RESULTS: Baseline characteristics were similar in all groups. Dosages of adrenergic agents decreased over time in all groups. A significant decrease in adrenergic requirements was seen in the CH group compared with the C group at t(4h) and t(proc). A trend toward decreased adrenergic requirements was noted in S compared with C at t(4h) and t(proc). Slightly more total organs were procured from S and CH compared with C. CONCLUSIONS: Significantly less adrenergic support was required with early use of CH. A similar (although nonsignificant) reduction was seen with S. The benefit(s) of CH vs corticosteroids alone remains uncertain and requires further study.

Laboratory markers predict bone loss in Crohn's disease: relationship to blood mononuclear cell function and nutritional status.

BACKGROUND: Crohn's disease is associated with reduced bone density. The power of simple markers of systemic inflammation to identify higher rates of bone loss, in Crohn's disease, is uncertain. This relationship and the role of circulating (peripheral blood) mononuclear cells were investigated in a case-control study. METHODS: Urinary deoxypyridinoline/creatinine and serum osteocalcin concentrations were compared in male and premenopausal females with "active" Crohn's disease (C-reactive protein > or = 10 and/or erythrocyte sedimentation rate > or = 20) (n = 22) and controls with "quiescent" Crohn's disease (C-reactive protein < 10 and erythrocyte sedimentation rate < 20) (n = 21). No patients were receiving corticosteroid therapy. Production of tumour necrosis factor-alpha, interferon-gamma and prostaglandin E(2) by peripheral blood mononuclear cells were measured. RESULTS: Active Crohn's disease was associated with a higher deoxypyridinoline/creatinine (P = 0.02) and deoxypyridinoline/creatinine:osteocalcin ratio (P =0.01) compared with quiescent Crohn's disease, but similar osteocalcin (P = 0.24). These were not explained by vitamin D status, dietary intake or nutritional status. However, production of interferon-gamma by concanavalin A-stimulated peripheral blood mononuclear cells was lower in active Crohn's disease (P = 0.02) and correlated negatively with the deoxypyridinoline/creatinine:osteocalcin ratio (r = -0.40, P = 0.004). CONCLUSION: In Crohn's disease, raised C-reactive protein and erythrocyte sedimentation rate may indicate higher rates of bone loss and, if persistent, the need to assess bone mass even where disease symptoms are mild. This may be partly explained by altered production of interferon-gamma by peripheral blood mononuclear cells.

Essential fatty acid status in paediatric Crohn's disease: relationship with disease activity and nutritional status.

BACKGROUND: Active paediatric Crohn's disease is associated with nutritional deficiencies and altered nutrient intake. The availability of essential fatty acids (linoleic and alpha-linolenic acids) or their derivatives (arachidonic and eicosapentaenoic acids) may alter in plasma and cell membrane phospholipid in protein-energy malnutrition in children and in Crohn's disease in adults. AIM: To investigate the relationship of fatty acid phospholipid profiles with disease activity and nutritional status in paediatric Crohn's disease. METHODS: The fatty acid (proportionate) composition of plasma and erythrocyte phosphatidylcholine was determined in 30 patients (10.3-17.0 years) stratified into active and quiescent Crohn's disease (paediatric Crohn's disease activity index) and high and low body mass (body mass index centile). RESULTS: In plasma phosphatidylcholine, active disease activity was associated with a lower level of alpha-linolenic acid compared with that in quiescent disease (P < 0.05). A body mass index below the 50th centile was associated with active Crohn's disease, low linoleic and alpha-linolenic acids and high arachidonic acid (P < 0.05) in plasma phosphatidylcholine, and low alpha-linolenic acid in erythrocyte phosphatidylcholine. These findings could not be explained through differences in habitual dietary fat intake. CONCLUSION: In paediatric Crohn's disease, a low body mass index centile and high disease activity are associated with altered profiles of essential fatty acids and their derivatives, which may reflect altered metabolic demand.