Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters

<p>Abstract</p> <p>Background</p> <p>The branched chain amino acid leucine is a potent stimulator of insulin secretion. Used in combination with glucose it can increase the insulin response and the post exercise re-synthesis of glycogen in man. Decreased plasma amino acid concentrations have been reported after intravenous or per oral administration of leucine in man as well as after a single per oral dose in horses. In man, a negative correlation between the insulin response and the concentrations of isoleucine, valine and methionine have been shown but results from horses are lacking. This study aims to determine the effect of repeated per oral administration with a mixture of glucose and leucine on the free amino acid profile and the insulin response in horses after glycogen-depleting exercise.</p> <p>Methods</p> <p>In a crossover design, after a glycogen depleting exercise, twelve Standardbred trotters received either repeated oral boluses of glucose, 1 g/kg body weight (BW) at 0, 2 and 4 h with addition of leucine 0.1 g/kg BW at 0 and 4 h (GLU+LEU), or repeated boluses of water at 0, 2 and 4 h (CON). Blood samples for analysis of glucose, insulin and amino acid concentrations were collected prior to exercise and over a 6 h post-exercise period. A mixed model approach was used for the statistical analyses.</p> <p>Results</p> <p>Plasma leucine, isoleucine, valine, tyrosine and phenylalanine concentrations increased after exercise. Post-exercise serum glucose and plasma insulin response were significantly higher in the GLU+LEU treatment compared to the CON treatment. Plasma leucine concentrations increased after supplementation. During the post-exercise period isoleucine, valine and methionine concentrations decreased in both treatments but were significantly lower in the GLU+LEU treatment. There was no correlation between the insulin response and the response in plasma leucine, isoleucine, valine and methionine.</p> <p>Conclusions</p> <p>Repeated post-exercise administration with a mixture of leucine and glucose caused a marked insulin response and altered the plasma amino acid profile in horses in a similar manner as described in man. However, the decreases seen in plasma amino acids in horses seem to be related more to an effect of leucine and not to the insulin response as seen in man.</p

Parents’ Disclosure of Their HIV Infection to Their Children in the Context of the Family

We interviewed 33 HIV-infected parents from the HIV Cost and Services Utilization Study (HCSUS), 27 of their minor children, 19 adult children, and 15 caregivers about the process of children learning that their parents were HIV positive. We summarize the retrospective descriptions of parents’ disclosure of their HIV status to their children, from the perspective of multiple family members. We analyzed transcripts of these interviews with systematic qualitative methods. Both parents and children reported unplanned disclosure experiences with positive and negative outcomes. Parents sometimes reported that disclosure was not as negative as they feared. However, within-household analysis showed disagreement between parents and children from the same household regarding disclosure outcomes. These findings suggest that disclosure should be addressed within a family context to facilitate communication and children’s coping. Parents should consider negative and positive outcomes, unplanned disclosure and children’s capacity to adapt after disclosure when deciding whether to disclose

Adipose Tissue Deficiency and Chronic Inflammation in Diabetic Goto-Kakizaki Rats

Type 2 diabetes (T2DM) is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK) rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals

Development of a context model to prioritize drug safety alerts in CPOE systems

Background: Computerized physician order entry systems (CPOE) can reduce the number of medication errors and adverse drug events (ADEs) in healthcare institutions. Unfortunately, they tend to produce a large number of partly irrelevant alerts, in turn leading to alert overload and causing alert fatigue. The objective of this work is to identify factors that can be used to prioritize and present alerts depending on the 'context' of a clinical situation. Methods: We used a combination of literature searches and expert interviews to identify and validate the possible context factors. The internal validation of the context factors was performed by calculating the inter-rater agreement of two researcher's classification of 33 relevant articles. Results: We developed a context model containing 20 factors. We grouped these context factors into three categories: characteristics of the patient or case (e. g. clinical status of the patient); characteristics of the organizational unit or user (e. g. professional experience of the user); and alert characteristics (e. g. severity of the effect). The internal validation resulted in nearly perfect agreement (Cohen's Kappa value of 0.97). Conclusion: To our knowledge, this is the first structured attempt to develop a comprehensive context model for prioritizing drug safety alerts in CPOE systems. The outcome of this work can be used to develop future tailored drug safety alerting in CPOE systems

Induction of Cellular Senescence by Doxorubicin Is Associated with Upregulated miR-375 and Induction of Autophagy in K562 Cells

BACKGROUND: Cellular senescence is a specialized form of growth arrest that is generally irreversible. Upregulated p16, p53, and p21 expression and silencing of E2F target genes have been characterized to promote the establishment of senescence. It can be further aided by the transcriptional repression of proliferation-associated genes by the action of HP1γ, HMGA, and DNMT proteins to produce a repressive chromatin environment. Therefore, senescence has been suggested to functions as a natural brake for tumor development and plays a critical role in tumor suppression and aging. METHODOLOGY/PRINCIPAL FINDINGS: An in vitro senescence model has been established by using K562 cells treated with 50 nM doxorubicin (DOX). Since p53 and p16 are homozygously deleted in the K562 cells, the DOX-induced senescence in K562 cells ought to be independent of p53 and p16-pRb pathways. Indeed, no change in the expression of the typical senescence-associated premalignant cell markers in the DOX-induced senescent K562 cells was found. MicroRNA profiling revealed upregulated miR-375 in DOX-induced senescent K562 cells. Treatment with miR-375 inhibitor was able to reverse the proliferation ability suppressed by DOX (p<0.05) and overexpression of miR-375 suppressed the normal proliferation of K562 cells. Upregulated miR-375 expression was associated with downregulated expression of 14-3-3zeta and SP1 genes. Autophagy was also investigated since DOX treatment was able to induce cells entering senescence and eventually lead to cell death. Among the 24 human autophagy-related genes examined, a 12-fold increase of ATG9B at day 4 and a 20-fold increase of ATG18 at day 2 after DOX treatment were noted. CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that in the absence of p53 and p16, the induction of senescence by DOX was associated with upregulation of miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Individual and contextual factors of influence on adherence to antiretrovirals among people attending public clinics in Rio de Janeiro, Brazil.

PMC3710472BACKGROUND: There are inconsistencies in the determinants of adherence to antiretrovirals (ARVs) across settings as well as a lack of studies that take into consideration factors beyond the individual level. This makes it necessary to examine factors holistically in multiple settings and populations while taking into consideration the particularities of each context, in order to understand the patterns of ARV adherence. This research explored ARV adherence and individual, relational and environmental-structural factors. METHODS: A cross-sectional survey was conducted from August 2008 through July 2009 among participants currently on ARVs recruited from 6 public health clinics, selected to maximize diversity in terms of caseload and location, representing the range of clinics within Rio de Janeiro city, Brazil. Multivariate logistic regression analysis was used to assess the association between our multilevel factors with ARV adherence among participants with complete cases (n = 632). RESULTS: Eighty-four percent of respondents reported adherence to all of their ARV doses in the last 4 days. Of the socio-demographic variables, those who had one child were positively associated with adherence (AOR 2.29 CI [1.33-3.94]). On the relational level, those with high social support (AOR 2.85 CI [1.50-5.41]) were positively associated with adherence to ARVs. On the environmental-structural level, we found gender was significant with women negatively associated with adherence to ARVs (AOR 0.58 CI [0.38-0.88]) while those with a high asset index (AOR 2.47 CI [1.79-3.40]) were positively associated with adherence to ARVs. CONCLUSIONS: This research highlights the importance of examining the multiple levels of influence on ARV adherence. Intervention research in lower and middle-income settings should address and evaluate the impact of attending to both gender and economic inequalities to improve ARV adherence, as well as relational areas such as the provision of social support.JH Libraries Open Access Fun

Despondency among HIV-positive older men and women in Uganda.

Forty people over 60 years of age took part in longitudinal research over the course of a year on the impact of the HIV epidemic in southern Uganda. In this paper we focus mainly on the data from 26 of the 40 who were HIV-positive. While we observed that feelings of depression were frequently experienced by many of the people in our study, the state of 'being depressed' was not constant. Participants regularly expressed economic frustration (because of a lack of money to buy food and other commodities including sugar and soap); medical problems (including those related to HIV) as well as old age, the burden of dependents (including concerns about school fees for grandchildren), feelings of sadness and isolation, and a lack of support from others, as well as stigma, whether real or perceived. However, while worries, sorrow and despondent thoughts were reported in many of the interviews across the study, moods fluctuated moving from happiness and hope, to sadness and despair, from month to month. Concerns regarding the psychological wellbeing amongst older people, including those living with HIV and older carers in Uganda deserve greater attention