Brain and Spinal Cord Interaction: Protective Effects of Exercise Prior to Spinal Cord Injury

We have investigated the effects of a spinal cord injury on the brain and spinal cord, and whether exercise provided before the injury could organize a protective reaction across the neuroaxis. Animals were exposed to 21 days of voluntary exercise, followed by a full spinal transection (T7–T9) and sacrificed two days later. Here we show that the effects of spinal cord injury go beyond the spinal cord itself and influence the molecular substrates of synaptic plasticity and learning in the brain. The injury reduced BDNF levels in the hippocampus in conjunction with the activated forms of p-synapsin I, p-CREB and p-CaMK II, while exercise prior to injury prevented these reductions. Similar effects of the injury were observed in the lumbar enlargement region of the spinal cord, where exercise prevented the reductions in BDNF, and p-CREB. Furthermore, the response of the hippocampus to the spinal lesion appeared to be coordinated to that of the spinal cord, as evidenced by corresponding injury-related changes in BDNF levels in the brain and spinal cord. These results provide an indication for the increased vulnerability of brain centers after spinal cord injury. These findings also imply that the level of chronic activity prior to a spinal cord injury could determine the level of sensory-motor and cognitive recovery following the injury. In particular, exercise prior to the injury onset appears to foster protective mechanisms in the brain and spinal cord

Chronic lymphocytic leukemia cells in lymph nodes show frequent NOTCH1 activation

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. Pathogenic mechanisms involve multiple external events (such as microenvironmental and antigenic stimuli) and internal events (genetic and epigenetic alterations) that are associated with the transformation, progression and evolution of CLL. CLL is characterized by an accumulation of mature B cells in peripheral blood, bone marrow and lymphoid tissues. Extracellular stimuli play an important role in the development and maintenance of neoplastic cells. B-CLL cells proliferate and activate pathogenic signaling pathways in anatomical structures known as proliferation centers, which are usually more conspicuous in involved lymph nodes.1 Its clinical course is quite heterogeneous, whereby some patients progress rapidly and have short survival, whereas others have a more stable clinical course that may not need treatment for years.This work was supported by grants from the Ministerio de Economía y Competitividad (MINECO) (SAF2013-47416-R) Instituto de Salud Carlos III (ISCIII)- FEDER – MINECO- AES (CP11/00018, PI10/00621, RD012/0036/0060), and Asociación Española contra el Cancer (AECC). MS-B is supported by a Miguel Servet contract from ISCIII-FEDER (CP11/00018). Salary support to SG is provided by CP11/00018, from ISCIII-FEDER. JG-R is supported by a predoctoral grant from the Fundación Investigación Puerta de Hierro.S

A Dopaminergic Gene Cluster in the Prefrontal Cortex Predicts Performance Indicative of General Intelligence in Genetically Heterogeneous Mice

Background: Genetically heterogeneous mice express a trait that is qualitatively and psychometrically analogous to general intelligence in humans, and as in humans, this trait co-varies with the processing efficacy of working memory (including its dependence on selective attention). Dopamine signaling in the prefrontal cortex (PFC) has been established to play a critical role in animals ’ performance in both working memory and selective attention tasks. Owing to this role of the PFC in the regulation of working memory, here we compared PFC gene expression profiles of 60 genetically diverse CD-1 mice that exhibited a wide range of general learning abilities (i.e., aggregate performance across five diverse learning tasks). Methodology/Principal Findings: Animals ’ general cognitive abilities were first determined based on their aggregate performance across a battery of five diverse learning tasks. With a procedure designed to minimize false positive identifications, analysis of gene expression microarrays (comprised of <25,000 genes) identified a small number (,20) of genes that were differentially expressed across animals that exhibited fast and slow aggregate learning abilities. Of these genes, one functional cluster was identified, and this cluster (Darpp-32, Drd1a, and Rgs9) is an established modulator of dopamine signaling. Subsequent quantitative PCR found that expression of these dopaminegic genes plus one vascular gene (Nudt6) were significantly correlated with individual animal’s general cognitive performance. Conclusions/Significance: These results indicate that D1-mediated dopamine signaling in the PFC, possibly through it

Lactancia materna ineficaz: prevalencia y factores asociados

RESUMENIntroducción: Es posible evitar muertes neonatales mediante la lactancia materna desde el primer día devida, pues la leche materna es el alimento óptimo para el lactante por su contenido nutricional necesariofavorecer el crecimiento y desarrollo. Objetivo: Determinar la prevalencia y factores asociados aldiagnóstico de enfermería “Lactancia materna ineficaz” en lactantes menores de 6 meses hospitalizados enuna institución de tercer nivel.Metodología: Estudio de corte transversal. Se seleccionaron 108 binomios(madre e hijo) hospitalizados en una institución de tercer nivel de atención en el año 2009, se aplicó unformato validado para identificar el diagnóstico. Se realizó análisis Rasch a las variables que representanlas características definitorias del diagnóstico, con el cual se creó una escala de 0 a 100 y se construyóun modelo de regresión lineal con las variables asociadas a la medida del diagnóstico.Resultados:la prevalencia del diagnóstico fue de 93,5 %, la característica definitoria más fácil de encontrar fueIncapacidad del lactante para agarrarse al pecho materno y la más difícil fue agitación y llanto del lactantedentro de la primera hora después de la lactancia materna. La regresión lineal mostró factores asociadoscomo: género femenino, peso del lactante y necesidad de la madre de ir a orinar.Conclusiones: Existeuna tendencia desfavorable tanto en la prevalencia como en la duración de la lactancia materna para loslactantes hospitalizados; la promoción de la lactancia materna debe ser un trabajo interdisciplinario;modificar las normas hospitalarias favoreciendo el contacto del binomio y la puesta temprana al pechomaterno. Salud UIS 2011; 43 (3): 271-279Palabras clave: Lactancia materna, diagnóstico de enfermería, lactante, prevalencia,factores asociadosABSTRACTIntroduction: neonatal deaths can be prevented by breastfeeding from the first day of life, as is the optimal foodfor infants by their nutritional content required for better growth and development.Objective: To determine theprevalence and associated factors with nursing diagnosis “ineffective breastfeeding” in infants under than 6 monthshospitalized in a tertiary institution.Methodology: Cross sectional study. We selected 108 pairs (mother and child)hospitalized in an institution of tertiary care in 2009, we applied a validated format to identify the diagnosis. Raschanalysis was performed for variables that represent the defining characteristics of the diagnosis, which created ascale of 0 to 100 and built a linear regression model the variables associated with the extent of diagnosis.Results:Prevalence of diagnosis was 93,5 %, the defining characteristic was easier to find the infant’s inability to hold onto the breast and the hardest was shaking and crying of the infant within the first hour after breastfeeding. Linearregression was associated factors such as: female gender, weight infant and the mother need to urinate.Conclusions:There is an unfavorable trend in both the prevalence and duration of breastfeeding for infants hospitalized, promotionof breastfeeding should be an interdisciplinary, modify hospital policies favoring the contact of the binomial and theearly start to the chest maternal. Salud UIS 2011; 43 (3): 271-279Keywords: Breastfeeding, nursing diagnosis, infant, prevalence, associated factor

Lactancia materna ineficaz: prevalencia y factores asociados

RESUMENIntroducción: Es posible evitar muertes neonatales mediante la lactancia materna desde el primer día devida, pues la leche materna es el alimento óptimo para el lactante por su contenido nutricional necesariofavorecer el crecimiento y desarrollo. Objetivo: Determinar la prevalencia y factores asociados aldiagnóstico de enfermería “Lactancia materna ineficaz” en lactantes menores de 6 meses hospitalizados enuna institución de tercer nivel.Metodología: Estudio de corte transversal. Se seleccionaron 108 binomios(madre e hijo) hospitalizados en una institución de tercer nivel de atención en el año 2009, se aplicó unformato validado para identificar el diagnóstico. Se realizó análisis Rasch a las variables que representanlas características definitorias del diagnóstico, con el cual se creó una escala de 0 a 100 y se construyóun modelo de regresión lineal con las variables asociadas a la medida del diagnóstico.Resultados:la prevalencia del diagnóstico fue de 93,5 %, la característica definitoria más fácil de encontrar fueIncapacidad del lactante para agarrarse al pecho materno y la más difícil fue agitación y llanto del lactantedentro de la primera hora después de la lactancia materna. La regresión lineal mostró factores asociadoscomo: género femenino, peso del lactante y necesidad de la madre de ir a orinar.Conclusiones: Existeuna tendencia desfavorable tanto en la prevalencia como en la duración de la lactancia materna para loslactantes hospitalizados; la promoción de la lactancia materna debe ser un trabajo interdisciplinario;modificar las normas hospitalarias favoreciendo el contacto del binomio y la puesta temprana al pechomaterno. Salud UIS 2011; 43 (3): 271-279Palabras clave: Lactancia materna, diagnóstico de enfermería, lactante, prevalencia,factores asociadosABSTRACTIntroduction: neonatal deaths can be prevented by breastfeeding from the first day of life, as is the optimal foodfor infants by their nutritional content required for better growth and development.Objective: To determine theprevalence and associated factors with nursing diagnosis “ineffective breastfeeding” in infants under than 6 monthshospitalized in a tertiary institution.Methodology: Cross sectional study. We selected 108 pairs (mother and child)hospitalized in an institution of tertiary care in 2009, we applied a validated format to identify the diagnosis. Raschanalysis was performed for variables that represent the defining characteristics of the diagnosis, which created ascale of 0 to 100 and built a linear regression model the variables associated with the extent of diagnosis.Results:Prevalence of diagnosis was 93,5 %, the defining characteristic was easier to find the infant’s inability to hold onto the breast and the hardest was shaking and crying of the infant within the first hour after breastfeeding. Linearregression was associated factors such as: female gender, weight infant and the mother need to urinate.Conclusions:There is an unfavorable trend in both the prevalence and duration of breastfeeding for infants hospitalized, promotionof breastfeeding should be an interdisciplinary, modify hospital policies favoring the contact of the binomial and theearly start to the chest maternal. Salud UIS 2011; 43 (3): 271-279Keywords: Breastfeeding, nursing diagnosis, infant, prevalence, associated factor

Lactancia materna ineficaz: prevalencia y factores asociados

RESUMENIntroducción: Es posible evitar muertes neonatales mediante la lactancia materna desde el primer día devida, pues la leche materna es el alimento óptimo para el lactante por su contenido nutricional necesariofavorecer el crecimiento y desarrollo. Objetivo: Determinar la prevalencia y factores asociados aldiagnóstico de enfermería “Lactancia materna ineficaz” en lactantes menores de 6 meses hospitalizados enuna institución de tercer nivel.Metodología: Estudio de corte transversal. Se seleccionaron 108 binomios(madre e hijo) hospitalizados en una institución de tercer nivel de atención en el año 2009, se aplicó unformato validado para identificar el diagnóstico. Se realizó análisis Rasch a las variables que representanlas características definitorias del diagnóstico, con el cual se creó una escala de 0 a 100 y se construyóun modelo de regresión lineal con las variables asociadas a la medida del diagnóstico.Resultados:la prevalencia del diagnóstico fue de 93,5 %, la característica definitoria más fácil de encontrar fueIncapacidad del lactante para agarrarse al pecho materno y la más difícil fue agitación y llanto del lactantedentro de la primera hora después de la lactancia materna. La regresión lineal mostró factores asociadoscomo: género femenino, peso del lactante y necesidad de la madre de ir a orinar.Conclusiones: Existeuna tendencia desfavorable tanto en la prevalencia como en la duración de la lactancia materna para loslactantes hospitalizados; la promoción de la lactancia materna debe ser un trabajo interdisciplinario;modificar las normas hospitalarias favoreciendo el contacto del binomio y la puesta temprana al pechomaterno. Salud UIS 2011; 43 (3): 271-279Palabras clave: Lactancia materna, diagnóstico de enfermería, lactante, prevalencia,factores asociadosABSTRACTIntroduction: neonatal deaths can be prevented by breastfeeding from the first day of life, as is the optimal foodfor infants by their nutritional content required for better growth and development.Objective: To determine theprevalence and associated factors with nursing diagnosis “ineffective breastfeeding” in infants under than 6 monthshospitalized in a tertiary institution.Methodology: Cross sectional study. We selected 108 pairs (mother and child)hospitalized in an institution of tertiary care in 2009, we applied a validated format to identify the diagnosis. Raschanalysis was performed for variables that represent the defining characteristics of the diagnosis, which created ascale of 0 to 100 and built a linear regression model the variables associated with the extent of diagnosis.Results:Prevalence of diagnosis was 93,5 %, the defining characteristic was easier to find the infant’s inability to hold onto the breast and the hardest was shaking and crying of the infant within the first hour after breastfeeding. Linearregression was associated factors such as: female gender, weight infant and the mother need to urinate.Conclusions:There is an unfavorable trend in both the prevalence and duration of breastfeeding for infants hospitalized, promotionof breastfeeding should be an interdisciplinary, modify hospital policies favoring the contact of the binomial and theearly start to the chest maternal. Salud UIS 2011; 43 (3): 271-279Keywords: Breastfeeding, nursing diagnosis, infant, prevalence, associated factor

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Diagnostic, etiologic, and genetic aspects of congenital ichthyoses at birth: Characteristics of the ECEMC cases

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCThe Ichthyoses constitutes a large family of genetic skin diseases characterized by dry skin and variable degrees of blisters and scales. There are at least twenty varieties of ichthyosis, with a wide range of severity and associated symptoms, and genetic heterogeneity (autosomal dominant, autosomal recessive, and X-linked inheritance). The clinical symptoms, which are non-specific, may not be apparent. We have attempted to provide a classification of the ichthyoses and some guidance for the diagnosis and management of these conditions. The present classification is based in the type of alteration of the skin layer, the molecular findings, the biochemical characteristics, and the family history.There are three main categories, which include different subgroups of ichthyoses: 1) Those that are caused by an altered process of keratinocytic diferenciation (altered intermediate filaments/keratins). This category includes the following subgroups: a) Harlequin fetus; b) bullous erythroderma ichthyosiformis congenital; c) Ichthyosis bullosa of Siemens; d) Ichthyosis hystrix of Curth-Macklin; and e) Ichthyosis vulgaris. 2) Those that are caused by a deficient formation of the cornified envelope (transglutaminase 1 enzyme deficiency). In this category we include two main subgrups: a) Lamellar ichthyosis AR, which includes i) ichthyosis lamellar (IL1, IL2, IL3, IL4, and IL5), and ii) ichthyosiform erythroderma congenital nonbullous, and b) Nonlamellar ichthyosis and nonerythrodermic congenital ichthyosis AR. 3) Those caused by an abnormal steroid sulfatase (X-linked Ichtyosis). In spite of having only data at birth and the lack of molecular analysis, we attempted to classify the ECEMC cases according to this classification using available clinical data. We also calculated the frequency of this disease identified at birth, and provide some guidance for the clinical diagnosis, the management of the affected newborn, and the information that should be offered to the parents.N

Prevalence, Incidence, and Outcomes of Hyperkalaemia in Patients with Chronic Heart Failure and Reduced Ejection Fraction from a Spanish Multicentre Study: SPANIK-HF Design and Baseline Characteristics

[Abstract] Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m2, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1–5.4 mEq/L = 13.8%, 5.5–5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment.AstraZeneca Farmacéutica; ESR-17-1324