The Canine POMC Gene, Obesity in Labrador Retrievers and Susceptibility to Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) in dogs is a common endocrinopathy with a complex genetic architecture. Disease susceptibility in several breeds is associated with polymorphisms in immune response genes, but in the Labrador retriever breed, no genetic associations with DM have been identified. A deletion in the pro-opiomelanocortin (POMC) gene in Labrador retrievers is associated with increased appetite and risk of obesity. HYPOTHESIS/OBJECTIVES: To characterize the POMC deletion in Labrador retrievers, to develop a simple genetic test for this mutation, and to test the hypothesis that the POMC gene deletion is associated with an increased risk of DM in this breed. ANIMALS: Sixty-one non-diabetic Labrador retrievers aged >6 years and 57 Labrador retrievers with DM. METHODS: Case-control genotyping study to compare the frequency of the POMC deletion in dogs with and without DM. After polymerase chain reaction (PCR) and sequencing to characterize the mutation, a PCR-based test was developed and validated using 2 different restriction fragment length polymorphism assays. RESULTS: A 14-base-pair deletion was confirmed and localized to exon 3 of the canine POMC gene. A PCR-based test for the deletion was successfully developed. There was no association between the presence of the POMC deletion mutation and DM in this population of Labrador retriever dogs (P = .31). CONCLUSIONS AND CLINICAL IMPORTANCE: This study adds to the existing scientific literature indicating that there is little evidence for a direct link between obesity and DM in dogs

Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo

Condições de vida e vocabulário receptivo em crianças de dois a cinco anos

OBJECTIVE: To assess the receptive vocabulary of children aged between two years and six months and five years and eleven months who were attending childcare centers and kindergarten schools. METHODS: An analytical cross-sectional study was carried out in the municipality of Embu, Southeastern Brazil. The Peabody Picture Vocabulary Test and analysis of factors associated with children's performance were applied. The sample consisted of 201 children of both genders, aged between two and six years. Statistical analysis was performed using multivariate analysis and logistic regression model. The dependent variable analyzed was test performance and the independent variables were child's age, mother's level of education and family socio-demographic characteristics. RESULTS: It was observed that 44.3% of the children had performances in the test that were below what would be expected for their age. The factors associated with the best performances in the test were child's age (OR=2.4; 95% CI: 1.6-3.5) and mother's education level (OR= 3.2; 95% CI: 1.3-7.4). CONCLUSIONS: Mother's education level is important for child's language development. Settings such as childcare and kindergarten schools are protective factors for child development in families of low income and education.OBJETIVO: Avaliar o vocabulário receptivo de crianças de dois anos e seis meses a cinco anos e 11 meses que freqüentam creches e pré-escolas. MÉTODOS: Estudo transversal e analítico realizado no município de Embu, Estado de São Paulo. Utilizou-se o Teste de Vocabulário por Imagem Peabody e análise de fatores associados ao desempenho. A amostra foi constituída de 201 crianças de ambos os sexos, com idade entre dois e seis anos. Foram realizados análise multivariada e modelo de regressão logística. A variável dependente analisada foi o desempenho no teste e as variáveis independentes foram a idade da criança, tempo de escolaridade e série, e características sociodemográficas de suas famílias. RESULTADOS: Observou-se que 44,3% das crianças apresentaram desempenho inferior ao esperado para a idade no teste e os fatores associados ao melhor desempenho foram a idade da criança (OR=2,4; IC 95%: 1,6-3,5) e a escolaridade materna (OR=3,2; IC 95%: 1,3-7,4). CONCLUSÕES: A escolaridade maternal é importante no desenvolvimento de linguagem da criança. As instituições como creches e pré- escolas são fatores de proteção do desenvolvimento infantil em famílias de baixa renda e com baixa escolaridade.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FonoaudiologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP, EPM, Depto. de FonoaudiologiaUNIFESP, EPM, Depto. de PediatriaSciEL

Renal Transplant Immunosuppression Impairs Natural Killer Cell Function In Vitro and In Vivo

Background: Despite an increasing awareness of the importance of innate immunity, the roles of natural killer (NK) cells in transplant rejection and antiviral and cancer immunity during immunosuppression have not been clearly defined. Methods: To address this issue we have developed a quantitative assay of NK cell function that can be used on clinical samples and have studied the influence of immunosuppression on NK cell function. NK cell degranulation and intracellular interferon (IFN)-c production were determined by flow cytometry of peripheral blood samples. Results: Overnight ex vivo treatment of peripheral blood cells from healthy controls with ciclosporin or tacrolimus inhibited NK cell degranulation and IFN-c production in a dose-dependent manner. A similar impairment of function was seen in NK cells from patients treated in vivo with calcineurin inhibitors. In the early post-transplant period, there was a variable reduction of NK cell counts after treatment with alemtuzumab and basiliximab. Conclusions: The functional inhibition of NK cells in early transplant patients coincides with the period of maximum susceptibility to viral infections. The ability to assay NK cell function in clinical samples allows assessment of the impact of immunosuppressio

Tissue-engineered tracheal replacement in a child: a 4-year follow-up study

In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs

La evolución del derecho a la educación en Colombia entre 1820 a 1876, como un derecho económico, social y cultural

In examining the evolution of the right to education in New Granada, Gran Colombia and the United States of Colombia, a major effort is evidenced by Francisco de Paula Santander, Mariano Ospina Rodriguez to promote the development of education as a right which should be free and compulsory.However, the project initiated by Santander Ospina Rodriguez and other presidents of the period covered from 1820 to 1876, is to prevent the social, political, cultural and civil wars that were designed to search for autonomy, freedom and independence.Al examinar la evolución del derecho a la educación en la Nueva Granada, la Gran Colombia y los Estados Unidos de Colombia, se evidencia un importante esfuerzo por parte de Francisco de Paula Santander y Mariano Ospina Rodríguez de promover el desarrollo de la educación como un derecho que debía ser gratuito y obligatorio.Sin embargo, el proyecto iniciado por Santander y Ospina Rodríguez y demás presidentes de la época comprendida entre 1820 a 1876, tiene como obstáculo los problemas sociales, políticos, culturales y las guerras civiles que tenían como fin la búsqueda de la autonomía, libertad e independencia

Increasing body mass index from age 5 to 14 years predicts asthma among adolescents: evidence from a birth cohort study

Background:Obesity and asthma are common disorders, and the prevalence of both has increased in recent decades. It has been suggested that increases in the prevalence of obesity might in part explain the increase in asthma prevalence. This study aims to examine the prospective association between change in body mass index (BMI) z-score between ages 5 and 14 years and asthma symptoms at 14 years. Methods:Data was taken from the Mater University Study of Pregnancy and its outcomes (MUSP), a birth cohort of 7223 mothers and children started in Brisbane (Australia) in 1981. BMI was measured at age 5 and 14 years. Asthma was assessed from maternal reports of symptoms at age 5 and 14 years. In this study analyses were conducted on 2911 participants who had information on BMI and asthma at both ages. Results: BMI z-score at age 14 and the change in BMI z-score from age 5 to 14–years were positively associated with asthma symptoms at age 14 years, whereas BMI z-score at age 5 was not associated with asthma at age 14. Adjustment for a range of early-life exposures did not substantially alter these findings. The association between change in BMI z-score with asthma symptoms at 14 years appeared stronger for male subjects compared with female subjects but there was no statistical evidence for a sex difference (P=0.36). Conclusions: Increase in BMI z-score between age 5 and 14 years is associated with increased risk of asthma symptoms in adolescence

Use of remote sensing to identify spatial risk factors for malaria in a region of declining transmission: a cross-sectional and longitudinal community survey

<p>Abstract</p> <p>Background</p> <p>The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa. Further malaria control will require targeted control strategies based on evidence of risk. The objective of this study was to identify environmental risk factors for malaria transmission using remote sensing technologies to guide malaria control interventions in a region of declining burden of malaria.</p> <p>Methods</p> <p>Satellite images were used to construct a sampling frame for the random selection of households enrolled in prospective longitudinal and cross-sectional surveys of malaria parasitaemia in Southern Province, Zambia. A digital elevation model (DEM) was derived from the Shuttle Radar Topography Mission version 3 DEM and used for landscape characterization, including landforms, elevation, aspect, slope, topographic wetness, topographic position index and hydrological models of stream networks.</p> <p>Results</p> <p>A total of 768 individuals from 128 randomly selected households were enrolled over 21 months, from the end of the rainy season in April 2007 through December 2008. Of the 768 individuals tested, 117 (15.2%) were positive by malaria rapid diagnostic test (RDT). Individuals residing within 3.75 km of a third order stream were at increased risk of malaria. Households at elevations above the baseline elevation for the region were at decreasing risk of having RDT-positive residents. Households where new infections occurred were overlaid on a risk map of RDT positive households and incident infections were more likely to be located in high-risk areas derived from prevalence data. Based on the spatial risk map, targeting households in the top 80^thpercentile of malaria risk would require malaria control interventions directed to only 24% of the households.</p> <p>Conclusions</p> <p>Remote sensing technologies can be used to target malaria control interventions in a region of declining malaria transmission in southern Zambia, enabling a more efficient use of resources for malaria elimination.</p

Physiological Induction of Regulatory Qa-1-Restricted CD8+ T Cells Triggered by Endogenous CD4+ T Cell Responses

T cell-dependent autoimmune diseases are characterized by the expansion of T cell clones that recognize immunodominant epitopes on the target antigen. As a consequence, for a given autoimmune disorder, pathogenic T cell clones express T cell receptors with a limited number of variable regions that define antigenic specificity. Qa-1, a MHC class I-like molecule, presents peptides from the variable region of TCRs to Qa-1-restricted CD8+ T cells. The induction of Vß-specific CD8+ T cells has been harnessed in an immunotherapeutic strategy known as the “T cell vaccination” (TCV) that comprises the injection of activated and attenuated CD4+ T cell clones so as to induce protective CD8+ T cells. We hypothesized that Qa-1-restricted CD8+ regulatory T cells could also constitute a physiologic regulatory arm of lymphocyte responses upon expansion of endogenous CD4+ T cells, in the absence of deliberate exogenous T cell vaccination. We immunized mice with two types of antigenic challenges in order to sequentially expand antigen-specific endogenous CD4+ T cells with distinct antigenic specificities but characterized by a common Vß chain in their TCR. The first immunization was performed with a non-self antigen while the second challenge was performed with a myelin-derived peptide known to drive experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. We show that regulatory Vß-specific Qa-1-restricted CD8+ T cells induced during the first endogenous CD4+ T cell responses are able to control the expansion of subsequently mobilized pathogenic autoreactive CD4+ T cells. In conclusion, apart from the immunotherapeutic TCV, Qa-1-restricted specialized CD8+ regulatory T cells can also be induced during endogenous CD4+ T cell responses. At variance with other regulatory T cell subsets, the action of these Qa-1-restricted T cells seems to be restricted to the immediate re-activation of CD4+ T cells

Altered Dopamine and Serotonin Metabolism in Motorically Asymptomatic R6/2 Mice

The pattern of cerebral dopamine (DA) abnormalities in Huntington disease (HD) is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD