Perceptions and experiences of nursing students communicating with people living with dementia: The validation, emotion, reassure, activity (VERA) communication skills framework.

BACKGROUND: There is an increased risk with advancing age that degenerative conditions such as dementia will affect a person's capacity to communicate. Thus, there is increased possibility that nursing students will be caring for this client group and will need to have the skills to communicate effectively. The Validation, Emotion, Reassure, Activity (VERA) framework is a communication tool developed for this purpose. OBJECTIVES: This pilot study explored nursing students' perceptions and experiences of communicating with people with dementia incorporating the VERA communication skills framework. METHODS: Using a descriptive qualitative approach, second year undergraduate general nursing students were eligible for inclusion if they were assigned to complete their 4-week clinical placement in the designated research site and were willing to participate. Students allocated to the designated research site (n = 6) in semester 1 received standard communication skills as part of the undergraduate programme and students allocated (n = 10) in semester 2 received 2.5 h of additional communication skills based on the VERA framework. Data were analysed using framework analysis as described by Ritchie & Spencer. RESULTS: The findings showed that students in both groups had initial reservations about communicating with people living with dementia. They employed several strategies including nonverbal techniques, distraction, reminiscence and life story work. However, students who received the VERA communication training felt more prepared to engage in these strategies because of the VERA training. CONCLUSION: With increasing numbers of people with dementia accessing health care, it is crucial that future nursing staff are equipped to meet the specific care needs of this population; which includes effective communication. The VERA framework can be useful to structure communication for nursing students. IMPLICATION FOR PRACTICE: The VERA training may be considered a useful framework for increasing undergraduate nursing students' knowledge and confidence in advance of clinical placements in older person's services. Nursing staff should continue to support students on clinical placements which involve caring for people with dementia and be cognisant of the trepidation students may have when first meeting this client group.

14-3-3θ Does Not Protect against Behavioral or Pathological Deficits in Alzheimer's Disease Mouse Models.

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with synaptic dysfunction and dendritic spine loss and the pathologic hallmarks of ß-amyloid (Aß) plaques and hyperphosphorylated tau tangles. 14-3-3 proteins are a highly conserved family of proteins whose functions include regulation of protein folding, neuronal architecture, and synaptic function. Additionally, 14-3-3s interact with both Aß and tau, and reduced levels of 14-3-3s have been shown in the brains of AD patients and in AD mouse models. Here, we examine the neuroprotective potential of the 14-3-3θ isoform in AD models. We demonstrate that 14-3-3θ overexpression is protective and 14-3-3θ inhibition is detrimental against oligomeric Aß-induced neuronal death in primary cortical cultures. Overexpression of 14-3-3θ using an adeno-associated viral (AAV) vector failed to improve performance on behavioral tests, improve Aß pathology, or affect synaptic density in the J20 AD mouse model. Similarly, crossing a second AD mouse model, the AppNL-G-F knock-in (APP KI) mouse, with 14-3-3θ transgenic mice failed to rescue behavioral deficits, reduce Aß pathology, or impact synaptic density in the APP KI mouse model. 14-3-3θ is likely partially insolubilized in the APP models, as demonstrated by proteinase K digestion. These findings do not support increasing 14-3-3θ expression as a therapeutic approach for AD.

A Glucose-Only Model to Extract Physiological Information from Postprandial Glucose Profiles in Subjects with Normal Glucose Tolerance.

BACKGROUND: Current mathematical models of postprandial glucose metabolism in people with normal and impaired glucose tolerance rely on insulin measurements and are therefore not applicable in clinical practice. This research aims to develop a model that only requires glucose data for parameter estimation while also providing useful information on insulin sensitivity, insulin dynamics and the meal-related glucose appearance (GA). METHODS: The proposed glucose-only model (GOM) is based on the oral minimal model (OMM) of glucose dynamics and substitutes the insulin dynamics with a novel function dependant on glucose levels and GA. A Bayesian method and glucose data from 22 subjects with normal glucose tolerance are utilised for parameter estimation. To validate the results of the GOM, a comparison to the results of the OMM, obtained by using glucose and insulin data from the same subjects is carried out. RESULTS: The proposed GOM describes the glucose dynamics with comparable precision to the OMM with an RMSE of 5.1 ± 2.3 mg/dL and 5.3 ± 2.4 mg/dL, respectively and contains a parameter that is significantly correlated to the insulin sensitivity estimated by the OMM (r = 0.7) Furthermore, the dynamic properties of the time profiles of GA and insulin dynamics inferred by the GOM show high similarity to the corresponding results of the OMM. CONCLUSIONS: The proposed GOM can be used to extract useful physiological information on glucose metabolism in subjects with normal glucose tolerance. The model can be further developed for clinical applications to patients with impaired glucose tolerance under the use of continuous glucose monitoring data.

14-3-3 mitigates alpha-synuclein aggregation and toxicity in the in vivo preformed fibril model.

Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies that pathologically define a group of disorders known as synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies. αSyn is hypothesized to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it can template the misfolding of endogenous αsyn upon cell internalization. 14-3-3 proteins are a family of highly expressed brain proteins that are neuroprotective in multiple PD models. We have previously shown that 14-3-3θ acts as a chaperone to reduce αsyn aggregation, cell-to-cell transmission, and neurotoxicity in the in vitro pre-formed fibril (PFF) model. In this study, we expanded our studies to test the impact of 14-3-3s on αsyn toxicity in the in vivo αsyn PFF model. We used both transgenic expression models and adenovirus associated virus (AAV)-mediated expression to examine whether 14-3-3 manipulation impacts behavioral deficits, αsyn aggregation, and neuronal counts in the PFF model. 14-3-3θ transgene overexpression in cortical and amygdala regions rescued social dominance deficits induced by PFFs at 6 months post injection, whereas 14-3-3 inhibition by transgene expression of the competitive 14-3-3 peptide inhibitor difopein in the cortex and amygdala accelerated social dominance deficits. The behavioral rescue by 14-3-3θ overexpression was associated with delayed αsyn aggregation induced by PFFs in these brain regions. Conversely, 14-3-3 inhibition by difopein in the cortex and amygdala accelerated αsyn aggregation and reduction in NECAB1-positive neuron counts induced by PFFs. 14-3-3θ overexpression by AAV in the substantia nigra (SN) also delayed αsyn aggregation in the SN and partially rescued PFF-induced reduction in tyrosine hydroxylase (TH)-positive dopaminergic cells in the SN. 14-3-3 inhibition in the SN accelerated nigral αsyn aggregation and enhanced PFF-induced reduction in TH-positive dopaminergic cells. These data indicate a neuroprotective role for 14-3-3θ against αsyn toxicity in vivo.

Bayesian parameter estimation in the oral minimal model of glucose dynamics from non-fasting conditions using a new function of glucose appearance.

BACKGROUND AND OBJECTIVE: The oral minimal model (OMM) of glucose dynamics is a prominent method for assessing postprandial glucose metabolism. The model yields estimates of insulin sensitivity and the meal-related appearance of glucose from insulin and glucose data after an oral glucose challenge. Despite its success, the OMM approach has several weaknesses that this paper addresses. METHODS: A novel procedure introducing three methodological adaptations to the OMM approach is proposed. These are: (1) the use of a fully Bayesian and efficient method for parameter estimation, (2) the model identification from non-fasting conditions using a generalised model formulation and (3) the introduction of a novel function to represent the meal-related glucose appearance based on two superimposed components utilising a modified structure of the log-normal distribution. The proposed modelling procedure is applied to glucose and insulin data from subjects with normal glucose tolerance consuming three consecutive meals in intervals of four hours. RESULTS: It is shown that the glucose effectiveness parameter of the OMM is, contrary to previous results, structurally globally identifiable. In comparison to results from existing studies that use the conventional identification procedure, the proposed approach yields an equivalent level of model fit and a similar precision of insulin sensitivity estimates. Furthermore, the new procedure shows no deterioration of model fit when data from non-fasting conditions are used. In comparison to the conventional, piecewise linear function of glucose appearance, the novel log-normally based function provides an improved model fit in the first 30 min of the response and thus a more realistic estimation of glucose appearance during this period. The identification procedure is implemented in freely accesible MATLAB and Python software packages. CONCLUSIONS: We propose an improved and freely available method for the identification of the OMM which could become the future standardard for the oral minimal modelling method of glucose dynamics.

Circulating lipids in men with type 2 diabetes following 3 days on a carbohydrate-free diet versus 3 days of fasting.

OBJECTIVE: We have been interested in determining the effects of dietary changes on fuel metabolism and regulation in men with type 2 diabetes mellitus (T2DM). In this study, the changes in 24-hr circulating lipid profiles were determined when the major fuel source was endogenous versus exogenous fat. METHODS: Seven males with T2DM were randomized in a crossover design with a 4-week washout period. A standard mixed (control) diet (30%fat:15%protein:55%carbohydrate) was provided initially. Subsequently, a 72-hr (3-day) fast, or a high fat (85%), 15% protein, essentially carbohydrate-free (CHO-free) diet was provided for 72 hr. Triacylglycerol (TAG), non-esterified fatty acids (NEFA), ß-hydroxybutyrate (bHB), and insulin-like growth factor-binding protein-1 (IGFBP-1) profiles were determined during the last 24 hr of intervention, as well as during the control diet. RESULTS: Regardless of the amount of dietary fat (30% vs 85%) and differences in 24-hr profiles, TAG, NEFA, and bHB all returned to the previous basal concentrations within 24 hr. TAGs and NEFAs changed only modestly with fasting; bHB was elevated and increasing. The IGFBP-1 profile was essentially unchanged with either diet but increased with fasting. CONCLUSION: A CHO-free diet resulted in a large increase in TAG and NEFA versus the control diet; however, both were cleared by the following morning. A negative NEFA profile occurred with the control diet. Thus, mechanisms are present to restore lipid concentrations to their original AM concentrations daily. Fasting resulted in stable concentrations, except for a continuing increase in bHB. Glucose and insulin, common fuel regulators, could not explain the results.

007 (x2)-3-3: 14-3-3 Targeted Compounds as Double Agents.

14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an exciting possibility of designing other 14-3-3 compounds to regulate critical 14-3-3 interactions.

ß-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3ß/tau cascade.

The brain noradrenergic system is critical for normal cognition and is affected at early stages in Alzheimer's disease (AD). Here, we reveal a previously unappreciated direct role of norepinephrine signaling in connecting ß-amyloid (Aß) and tau, two key pathological components of AD pathogenesis. Our results show that Aß oligomers bind to an allosteric site on α2A adrenergic receptor (α2AAR) to redirect norepinephrine-elicited signaling to glycogen synthase kinase 3ß (GSK3ß) activation and tau hyperphosphorylation. This norepinephrine-dependent mechanism sensitizes pathological GSK3ß/tau activation in response to nanomolar accumulations of extracellular Aß, which is 50- to 100-fold lower than the amount required to activate GSK3ß by Aß alone. The significance of our findings is supported by in vivo evidence in two mouse models, human tissue sample analysis, and longitudinal clinical data. Our study provides translational insights into mechanisms underlying Aß proteotoxicity, which might have strong implications for the interpretation of Aß clearance trial results and future drug design and for understanding the selective vulnerability of noradrenergic neurons in AD.

Telling a 'good or white lie': The views of people living with dementia and their carers.

OBJECTIVE: A common symptom of cognitive decline in people living with dementia, or people with memory problems, the cause of which has not yet been diagnosed, is the person repeatedly asking for loved ones who are deceased or making statements that are incorrect. Carers are then faced with a dilemma, do they avoid and distract or 'correct' the person and tell the 'truth', or tell a lie. This paper explores the concept of lying from the perspective of people living with dementia in the community and their informal/unpaid carers. METHODS: A descriptive qualitative study utilising focus groups to collect the data was conducted. Three focus group's with a purposive sample of people with memory problems (n = 14) and three focus group's with informal/unpaid carers (n = 18) were undertaken. Qualitative content analysis was used to analyse the data. RESULTS: All participants considered that blatant lying with the intention to deceive and do harm is not acceptable. However, telling a 'good lie' or 'white lie' to alleviate distress was in certain circumstances considered acceptable. The intention behind the 'lie' in their view had to be to do good, and the informal/unpaid carer telling the lie had to really 'know the person' and be cognisant of family preferences. Some informal/unpaid carers acknowledged that it may be acceptable for health care professionals to tell a 'good lie' or 'small lie' in certain circumstances. However, health professionals need to 'know the person' and need to consider informal/family caregivers' wishes. CONCLUSION: Lying was only considered acceptable in the context of knowing the person and when done with the intention not to harm or deceive, undertaken with empathy, and only for the purpose of mitigating the person living with dementia's distress.

Complex noradrenergic dysfunction in Alzheimer's disease: Low norepinephrine input is not always to blame.

The locus coeruleus-noradrenergic (LC-NA) system supplies the cerebral cortex with norepinephrine, a key modulator of cognition. Neurodegeneration of the LC is an early hallmark of Alzheimer's disease (AD). In this article, we analyze current literature to understand whether NA degeneration in AD simply leads to a loss of norepinephrine input to the cortex. With reported adaptive changes in the LC-NA system at the anatomical, cellular, and molecular levels in AD, existing evidence support a seemingly sustained level of extracellular NE in the cortex, at least at early stages of the long course of AD. We postulate that loss of the integrity of the NA system, rather than mere loss of NE input, is a key contributor to AD pathogenesis. A thorough understanding of NA dysfunction in AD has a large impact on both our comprehension and treatment of this devastating disease.

The amyloid precursor protein modulates α2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.

The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A-adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α2AAR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblastoma neuro-2A cells and primary superior cervical ganglion neurons, where APP is highly expressed, the lack of APP leads to a dramatic increase in plasma membrane recruitment of endogenous arrestin 3 following α2AAR activation. Concomitantly, agonist-induced internalization of α2AAR is significantly enhanced in these neuronal cells. Our study provided the first evidence that APP fine tunes GPCR signaling and trafficking. Given the important role of α2AAR in controlling norepinephrine release and response, this novel regulation of α2AAR by APP may have an impact on modulation of noradrenergic activity and sympathetic tone.-Zhang, F., Gannon, M., Chen, Y., Zhou, L., Jiao, K., Wang, Q. The amyloid precursor protein modulates α2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment.

The ghrelin and leptin responses to short-term starvation vs a carbohydrate-free diet in men with type 2 diabetes; a controlled, cross-over design study.

BACKGROUND: We recently have reported the 24-hour glucose, insulin and glucagon responses to a 72-hour fast compared to a 72-hour macronutrient-sufficient, carbohydrate-free diet in men with type 2 diabetes. The 72-hour time period was used because it is the time required for the major metabolic adjustments to a lack of food to be instituted. As part of that study, ghrelin and leptin responses were monitored. METHODS: Twenty-four-hour total ghrelin and overnight fasting leptin concentrations were determined in males with type 2 diabetes when ingesting a standard, mixed meal diet (control), followed by a carbohydrate-free diet for 72 h or were starved for 72 h, using a crossover design. RESULTS: A rise in ghrelin concentration before and a decrease after meals was present when the standard diet was ingested. However, in contrast to literature reports in normal subjects, a circadian variation was not apparent. Meal related changes were absent with starvation. A carbohydrate-free diet resulted in a daylong decrease in ghrelin. It also resulted in a 19 % decrease in the overnight fasting leptin concentration. Leptin was decreased 54 % with total starvation. CONCLUSION: Ingestion of a typical mixed-meal diet results in meal-related changes in ghrelin similar to those reported in normal subjects, although the circadian rhythm was not apparent. Except for the lack of meal-related changes, starvation did not change the concentration. A carbohydrate-free, high fat diet resulted in a daylong suppression of ghrelin. The leptin concentration was decreased by both the carbohydrate-free diet and starvation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01469104.

Spinophilin Is Indispensable for the α2B Adrenergic Receptor-Elicited Hypertensive Response.

The α2 adrenergic receptor (AR) subtypes are important for blood pressure control. When activated, the α2A subtype elicits a hypotensive response whereas the α2B subtype mediates a hypertensive effect that counteracts the hypotensive response by the α2A subtype. We have previously shown that spinophilin attenuates the α2AAR-dependent hypotensive response; in spinophilin null mice, this response is highly potentiated. In this study, we demonstrate that spinophilin impedes arrestin-dependent phosphorylation and desensitization of the α2BAR subtype by competing against arrestin binding to this receptor subtype. The Del301-303 α2BAR, a human variation that shows impaired phosphorylation and desensitization and is linked to hypertension in certain populations, exhibits preferential interaction with spinophilin over arrestin. Furthermore, Del301-303 α2BAR-induced ERK signaling is quickly desensitized in cells without spinophilin expression, showing a profile similar to that induced by the wild type receptor in these cells. Together, these data suggest a critical role of spinophilin in sustaining α2BAR signaling. Consistent with this notion, our in vivo study reveals that the α2BAR-elicited hypertensive response is diminished in spinophilin deficient mice. In arrestin 3 deficient mice, where the receptor has a stronger binding to spinophilin, the same hypertensive response is enhanced. These data suggest that interaction with spinophilin is indispensable for the α2BAR to elicit the hypertensive response. This is opposite of the negative role of spinophilin in regulating α2AAR-mediated hypotensive response, suggesting that spinophilin regulation of these closely related receptor subtypes can result in distinct functional outcomes in vivo. Thus, spinophilin may represent a useful therapeutic target for treatment of hypertension.

Noradrenergic dysfunction in Alzheimer's disease.

The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed.

Gynecomastia and drugs: a critical evaluation of the literature.

PURPOSE: A large number of medications have been implicated in the genesis of gynecomastia. However, gynecomastia is common in men, asymptomatic, increases with age, and is considered to be due to an increased estradiol/testosterone ratio. This complicates the interpretation of medication-related gynecomastia. Therefore, we have reviewed the literature in order to assess the data relating gynecomastia onset with utilization of specific medications. METHODS: The literature was searched in PubMed and the Ovid/Medline databases from the 1946 to January 2015 with the search terminology of "gynecomastia, drugs/medications." A few other articles were found and included. RESULTS: One hundred ten publications were reviewed. Sixty-three were single case reports. There were 24 population-based studies of which 8 were HIV-infected patients treated with antiretroviral agents. Among the case reports, 49 were for individual medications, and 2 were reports of antineoplastic or antiretroviral drug regimens. In the great majority, mastodynia with or without breast enlargement was present and referred to as gynecomastia. Generally, hormonal profiles could not explain the breast enlargement. The pain/tenderness and breast enlargement resolved spontaneously over time. CONCLUSION: Many different medications have been associated with the presence of "gynecomastia." Generally, it presents as a syndrome characterized by a single painful/tender breast (mastodynia) associated with breast enlargement and is transient. We suggest that these cases be referred to as an acute gynecomastia syndrome. This syndrome also occurs independent of medication use. Thus, in an individual patient, whether it is medication induced often remains uncertain. The pathogenesis remains unknown.

Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes.

OBJECTIVE: Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet. Improvement typically occurs soon after diet implementation. This rapid response could result from low fuel supply (calories), lower carbohydrate content of the weight-loss diet, and/or weight loss per se. To differentiate these effects, glucose, insulin, C-peptide and glucagon were determined during the last 24 h of a 3-day period without food (severe calorie restriction) and a calorie-sufficient, carbohydrate-free diet. RESEARCH DESIGN: Seven subjects with untreated type 2 diabetes were studied. A randomized-crossover design with a 4-week washout period between arms was used. METHODS: Results from both the calorie-sufficient, carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55% carbohydrate, 15% protein and 30% fat. RESULTS: The overnight fasting glucose concentration decreased from 196 (standard diet) to 160 (carbohydrate-free diet) to 127 mg/dl (fasting). The 24 h glucose and insulin area responses decreased by 35% and 48% on day 3 of the carbohydrate-free diet, and by 49% and 69% after fasting. Overnight basal insulin and glucagon remained unchanged. CONCLUSIONS: Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations. Carbohydrate restriction per se could account for 71% of the reduction. Insulin could not entirely explain the glucose responses. In the absence of carbohydrate, the net insulin response was 28% of the standard diet. Glucagon did not contribute to the metabolic adaptations observed.

α(2A) adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction.

Accumulation of amyloid ß (Aß) peptides in the brain is the key pathogenic factor driving Alzheimer's disease (AD). Endocytic sorting of amyloid precursor protein (APP) mediated by the vacuolar protein sorting (Vps10) family of receptors plays a decisive role in controlling the outcome of APP proteolytic processing and Aß generation. Here we report for the first time to our knowledge that this process is regulated by a G protein-coupled receptor, the α(2A) adrenergic receptor (α(2A)AR). Genetic deficiency of the α(2A)AR significantly reduces, whereas stimulation of this receptor enhances, Aß generation and AD-related pathology. Activation of α(2A)AR signaling disrupts APP interaction with a Vps10 family receptor, sorting-related receptor with A repeat (SorLA), in cells and in the mouse brain. As a consequence, activation of α(2A)AR reduces Golgi localization of APP and concurrently promotes APP distribution in endosomes and cleavage by ß secretase. The α(2A)AR is a key component of the brain noradrenergic system. Profound noradrenergic dysfunction occurs consistently in patients at the early stages of AD. α(2A)AR-promoted Aß generation provides a novel mechanism underlying the connection between noradrenergic dysfunction and AD. Our study also suggests α(2A)AR as a previously unappreciated therapeutic target for AD. Significantly, pharmacological blockade of the α(2A)AR by a clinically used antagonist reduces AD-related pathology and ameliorates cognitive deficits in an AD transgenic model, suggesting that repurposing clinical α(2A)R antagonists would be an effective therapeutic strategy for AD.

Interaction of ingested leucine with glycine on insulin and glucose concentrations.

The majority of individual amino acids increase insulin and attenuate the plasma glucose response when ingested with glucose. Objective. To determine whether ingestion of two amino acids simultaneously, with glucose, would result in an additive effect. Leucine (Leu) and glycine (Gly) were chosen because they were two of the most potent glucose-lowering amino acids when given individually. Materials and Methods. Nine subjects received test items on four separate days. The first was a water control, then 25 g glucose, or Leu + Gly (1 mmol/kg fat-free mass each) ±25 g glucose, in random order. Glucose, insulin, and glucagon were measured frequently for 2.5 hours. Net areas were calculated. Results. The glucose area response decreased by 66%. The insulin area response increased by 24% after ingestion of Leu + Gly + glucose compared to ingestion of glucose alone. The decrease in glucose response was not additive; the increase in insulin response was far less than additive when compared to previously published individual amino acid results. The glucagon concentration remained unchanged. Conclusion. There is an interaction between Leu and Gly that results in a markedly attenuated glucose response. This occurred with a very modest increase in insulin response. Changes in glucagon response could not explain the results. The mechanism is unknown.

Exploration of the meaning of connectedness for older people in long-term care in context of their quality of life: a review and commentary.

BACKGROUND: A link between 'quality of life' and 'connectedness' is emerging in the literature. However, there has been little debate on what 'connectedness' means and how it can be fostered in long-term care settings. This review examines the meaning of 'connectedness' in long-term care. AIM: This paper critically examines the meaning of 'connectedness' in the context of its contribution to the quality of life of older people living in long-term care settings. METHOD: Key databases (CINAHL, PsychInfo and Medline) were searched systematically. Fourteen papers and two book chapters met the inclusion criterion of papers exploring 'connectedness for older people in residential care'. CONCLUSIONS: The experience of connectedness for older people in long-term care settings is linked with quality of life and successful ageing. Fundamental prerequisites of connectedness for older people are: self-awareness, meaningful relationships with family and friends, involvement in meaningful activities and connections with wider society. However, barriers to these prerequisites are evident for many residents in long-term care settings. IMPLICATIONS FOR PRACTICE: Register and Herman (Advances in Nursing Science, 33, 2010, 53) identify six connections that combine to generate connectedness for older people. These connections are representative of the factors associated with increased quality of life for residents living in long-term care settings. The six connections are helpful in identifying areas to focus on when planning person-centred care.

Ingestion of leucine + phenylalanine with glucose produces an additive effect on serum insulin but less than additive effect on plasma glucose.

Most individual amino acids stimulate insulin secretion and attenuate the plasma glucose response when ingested with glucose. We determined whether ingestion of two amino acids simultaneously with glucose would result in an additive effect on the glucose area response compared with ingestion of amino acids individually. Leucine and phenylalanine were chosen because they were two of the most potent glucose-lowering amino acids when given individually. Eight healthy subjects were studied on four separate days. Test meals were given at 0800. The first meal was a water control. Subjects then received 25 g glucose or leucine + phenylalanine (1 mmol/kg fat free body mass each) ±25 g glucose in random order. Glucose, insulin and glucagon were measured frequently for 2.5 hours thereafter. Net areas under the curves were calculated using the mean fasting value as baseline. The insulin response to leucine + phenylalanine was additive. In contrast, the decrease in glucose response to leucine + phenylalanine + glucose was less than additive compared to the individual amino acids ingested with glucose. Interestingly, the insulin response to the combination was largely due to the leucine component, whereas the glucose response was largely due to the phenylalanine component. Glucose was unchanged when leucine or phenylalanine, alone or in combination, was ingested without glucose. This trial is registered with ClinicalTrials.gov NCT01471509.