The Neurotrophins and Their Role in Alzheimer’s Disease

Besides being essential for correct development of the vertebrate nervous system the neurotrophins also play a vital role in adult neuron survival, maintenance and regeneration. In addition they are implicated in the pathogenesis of certain neurodegenerative diseases, and may even provide a therapeutic solution for some. In particular there have been a number of studies on the involvement of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in the development of Alzheimer’s disease. This disease is of growing concern as longevity increases worldwide, with little treatment available at the moment to alleviate the condition. Memory loss is one of the earliest symptoms associated with Alzheimer’s disease. The brain regions first affected by pathology include the hippocampus, and also the entorhinal cortex and basal cholinergic nuclei which project to the hippocampus; importantly, all these areas are required for memory formation. Both NGF and BDNF are affected early in the disease and this is thought to initiate a cascade of events which exacerbates pathology and leads to the symptoms of dementia. This review briefly describes the pathology, symptoms and molecular processes associated with Alzheimer’s disease; it discusses the involvement of the neurotrophins, particularly NGF and BDNF, and their receptors, with changes in BDNF considered particularly in the light of its importance in synaptic plasticity. In addition, the possibilities of neurotrophin-based therapeutics are evaluated

Use of indirect calorimetry to evaluate utilization of energy in lactating Jersey dairy cattle consuming common coproducts

The use of coproducts as an alternative feed source is a common practice when formulating dairy rations. A study using 12 multiparous (79 ± 16 d in milk; mean ± standard deviation) lactating Jersey cows was conducted over 5 mo to evaluate the effects of dried distillers grains with solubles (DDGS) or canola meal on milk and gas production. A replicated 4 × 4 Latin square design was used to compare 4 dietary treatments. Treatments comprised a control (CON) containing no coproducts, a treatment diet containing 10% (dry matter basis) lowfat DDGS (LFDG), a treatment diet containing 10% high-fat DDGS (HFDG), and a 10% canola meal (CM) treatment. The crude fat content of the LFDG, HFDG, and CM treatments was 6.05 ± 0.379, 10.0 ± 0.134, and 3.46 ± 0.085%, respectively. Coproducts were included in partial replacement for corn and soybean meal. Indirect headbox-style calorimeters were used to estimate heat production. Dry matter intake and milk yield were similar between all treatments, averaging 17.4 ± 0.56 kg/d and 24.0 ± 0.80 kg, respectively. Milk urea N was affected by treatment and was highest in CON (20.6 mg/dL; 18.0, 19.9, and 18.1 ± 0.62 mg/dL in LFDG, CM, and HFDG, respectively). Heat production per unit of metabolic body weight tended to be affected by treatment and was lowest for CON, and diets containing coproducts were not different (192, 200, 215, and 204 ± 5.91 kcal/kg of metabolic body weight for CON, LFDG, CM, and HFDG, respectively). The concentration of metabolizable energy was affected by dietary treatment; specifically, HFDG did not differ from CON but was greater than LFDG and CM (2.58, 2.46, 2.29, and 2.27 ± 0.09 Mcal/kg for HFDG, CON, LFDG, and CM, respectively). The concentration of net energy balance (milk plus tissue) tended to be affected by dietary treatment; HFDG did not differ from either CON or LFDG, but it was higher than CM (1.38, 1.36, 1.14, and 1.06 ± 0.11 Mcal/kg for HFDG, CON, LFDG, and CM, respectively). Results of this study indicate that milk production and dry matter intake were not affected by feeding common coproducts and that differences may result in whole-animal energy use; fat content of DDGS is a major factor affecting this

Core competencies for pain management: results of an interprofessional consensus summit.

ObjectiveThe objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported.MethodsAn interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached.ResultsThe consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain.ConclusionsThese competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain

Cellular Hypertrophy and Increased Susceptibility to Spontaneous Calcium-Release of Rat Left Atrial Myocytes Due to Elevated Afterload

Atrial remodeling due to elevated arterial pressure predisposes the heart to atrial fibrillation (AF). Although abnormal sarcoplasmic reticulum (SR) function has been associated with AF, there is little information on the effects of elevated afterload on atrial Ca2+-handling. We investigated the effects of ascending aortic banding (AoB) on Ca2+-handling in rat isolated atrial myocytes in comparison to age-matched sham-operated animals (Sham). Myocytes were either labelled for ryanodine receptor (RyR) or loaded with fluo-3-AM and imaged by confocal microscopy. AoB myocytes were hypertrophied in comparison to Sham controls (P<0.0001). RyR labeling was localized to the z-lines and to the cell edge. There were no differences between AoB and Sham in the intensity or pattern of RyR-staining. In both AoB and Sham, electrical stimulation evoked robust SR Ca2+-release at the cell edge whereas Ca2+ transients at the cell center were much smaller. Western blotting showed a decreased L-type Ca channel expression but no significant changes in RyR or RyR phosphorylation or in expression of Na+/Ca2+ exchanger, SR Ca2+ ATPase or phospholamban. Mathematical modeling indicated that [Ca2+]i transients at the cell center were accounted for by simple centripetal diffusion of Ca2+ released at the cell edge. In contrast, caffeine (10 mM) induced Ca2+ release was uniform across the cell. The caffeine-induced transient was smaller in AoB than in Sham, suggesting a reduced SR Ca2+-load in hypertrophied cells. There were no significant differences between AoB and Sham cells in the rate of Ca2+ extrusion during recovery of electrically-stimulated or caffeine-induced transients. The incidence and frequency of spontaneous Ca2+-transients following rapid-pacing (4 Hz) was greater in AoB than in Sham myocytes. In conclusion, elevated afterload causes cellular hypertrophy and remodeling of atrial SR Ca2+-release

Process evaluation of appreciative inquiry to translate pain management evidence into pediatric nursing practice

Background Appreciative inquiry (AI) is an innovative knowledge translation (KT) intervention that is compatible with the Promoting Action on Research in Health Services (PARiHS) framework. This study explored the innovative use of AI as a theoretically based KT intervention applied to a clinical issue in an inpatient pediatric care setting. The implementation of AI was explored in terms of its acceptability, fidelity, and feasibility as a KT intervention in pain management. Methods A mixed-methods case study design was used. The case was a surgical unit in a pediatric academic-affiliated hospital. The sample consisted of nurses in leadership positions and staff nurses interested in the study. Data on the AI intervention implementation were collected by digitally recording the AI sessions, maintaining logs, and conducting individual semistructured interviews. Data were analysed using qualitative and quantitative content analyses and descriptive statistics. Findings were triangulated in the discussion. Results Three nurse leaders and nine staff members participated in the study. Participants were generally satisfied with the intervention, which consisted of four 3-hour, interactive AI sessions delivered over two weeks to promote change based on positive examples of pain management in the unit and staff implementation of an action plan. The AI sessions were delivered with high fidelity and 11 of 12 participants attended all four sessions, where they developed an action plan to enhance evidence-based pain assessment documentation. Participants labeled AI a 'refreshing approach to change' because it was positive, democratic, and built on existing practices. Several barriers affected their implementation of the action plan, including a context of change overload, logistics, busyness, and a lack of organised follow-up. Conclusions Results of this case study supported the acceptability, fidelity, and feasibility of AI as a KT intervention in pain management. The AI intervention requires minor refinements (e.g., incorporating continued follow-up meetings) to enhance its clinical utility and sustainability. The implementation process and effectiveness of the modified AI intervention require evaluation in a larger multisite study

The Effects of Aging on the Regulation of T-Tubular i Ca by Caveolin in Mouse Ventricular Myocytes

Aging is associated with diminished cardiac function in males. Cardiac excitation-contraction coupling in ventricular myocytes involves Ca influx via the Ca current (ICa) and Ca release from the sarcoplasmic reticulum, which occur predominantly at t-tubules. Caveolin-3 regulates t-tubular ICa, partly through protein kinase A (PKA), and both ICa and caveolin-3 decrease with age. We therefore investigated ICa and t-tubule structure and function in cardiomyocytes from male wild-type (WT) and caveolin-3-overexpressing (Cav-3OE) mice at 3 and 24 months of age. In WT cardiomyocytes, t-tubular ICa-density was reduced by ~50% with age while surface ICa density was unchanged. Although regulation by PKA was unaffected by age, inhibition of caveolin-3-binding reduced t-tubular ICa at 3 months, but not at 24 months. While Cav-3OE increased cardiac caveolin-3 protein expression ~2.5-fold at both ages, the age-dependent reduction in caveolin-3 (WT ~35%) was preserved in transgenic mice. Overexpression of caveolin-3 reduced t-tubular ICa density at 3 months but prevented further ICa loss with age. Measurement of Ca release at the t-tubules revealed that the triggering of local Ca release by t-tubular ICa was unaffected by age. In conclusion, the data suggest that the reduction in ICa density with age is associated with the loss of a caveolin-3-dependent mechanism that augments t-tubular ICa density

Cardiac-specific overexpression of caveolin-3 preserves t-tubular I _Ca during heart failure in mice

New findingsWhat is the central question of this study? What is the cellular basis of the protection conferred on the heart by overexpression of caveolin-3 (Cav-3 OE) against many of the features of heart failure normally observed in vivo? What is the main finding and its importance? Cav-3 overexpression has little effect in normal ventricular myocytes but reduces cellular hypertrophy and preserves t-tubular ICa , but not local t-tubular Ca2+ release, in heart failure induced by pressure overload in mice. Thus Cav-3 overexpression provides specific but limited protection following induction of heart failure, although other factors disrupt Ca2+ release.AbstractCaveolin-3 (Cav-3) is an 18&nbsp;kDa protein that has been implicated in t-tubule formation and function in cardiac ventricular myocytes. During cardiac hypertrophy and failure, Cav-3 expression decreases, t-tubule structure is disrupted and excitation-contraction coupling (ECC) is impaired. Previous work has suggested that Cav-3 overexpression (OE) is cardio-protective, but the effect of Cav-3 OE on these cellular changes is unknown. We therefore investigated whether Cav-3 OE in mice is protective against the cellular effects of pressure overload induced by 8&nbsp;weeks' transverse aortic constriction (TAC). Cav-3 OE mice developed cardiac dilatation, decreased stroke volume and ejection fraction, and hypertrophy and pulmonary congestion in response to TAC. These changes were accompanied by cellular hypertrophy, a decrease in t-tubule regularity and density, and impaired local Ca2+ release at the t-tubules. However, the extent of cardiac and cellular hypertrophy was reduced in Cav-3 OE compared to WT mice, and t-tubular Ca2+ current (ICa ) density was maintained. These data suggest that Cav-3 OE helps prevent hypertrophy and loss of t-tubular ICa following TAC, but that other factors disrupt local Ca2+ release

Levels of second hand smoke in pubs and bars by deprivation and food-serving status: a cross-sectional study from North West England

BACKGROUND: The UK government proposed introducing partial smokefree legislation for England with exemptions for pubs and bars that do not prepare and serve food. We set out to test the hypothesis that pubs from more deprived areas and non food-serving pubs have higher levels of particulate air pollution. METHODS: We conducted a cross sectional study in four mainly urban areas of the North West of England. We recruited a stratified random sample of 64 pubs divided into four groups based on whether their local population was affluent or deprived (using a UK area based deprivation measure), and whether or not they served food. The timing of air quality monitoring stratified to ensure similar distribution of monitoring by day of the week and time of evening between groups. We used a portable air quality monitor to collect fine particle (PM(2.5)) levels over a minimum of 30 minutes in areas where smoking was allowed,, and calculated mean time-time weighted average PM(2.5 )levels. RESULTS: Mean PM(2.5 )was 285.5 μg/m(3 )(95% CI 212.7 to 358.3). Mean levels in the four groups were: affluent food-serving pubs (n = 16) 188.1 μg/m(3 )(95%CI 128.1 to 248.1); affluent non food-serving (n = 16) 186.8 μg/m(3 )(95%CI 118.9 to 254.3); deprived food-serving (n = 17) 399.4 μg/m(3 )(95%CI 177.7 to 621.2); and deprived non food-serving (n = 15) 365.7 μg/m(3 )(195.6 to 535.7). Levels were higher in pubs in deprived communities: mean 383.6 μg/m(3 )(95% CI 249.2 to 518.0) vs 187.4 μg/m(3 )(144.8 to 229.9); geometric mean 245.2 μg/m(3 )vs 151.2 μg/m(3 )(p = 0.03). There was little difference in particulate levels between food and non food-serving pubs. CONCLUSION: This study adds to the evidence that the UK government’s proposals for partial smokefree legislation in England would offer the least protection to the most heavily exposed group - bar workers and customers in non food-serving pubs in deprived areas. The results suggest these proposals would work against the UK government’s stated aim to reduce health inequalities