Nicotinamide, an acetylcholinesterase uncompetitive inhibitor, protects the blood‒brain barrier and improves cognitive function in rats fed a hypercaloric diet.

Oxidative stress and inflammation induced by abundant consumption of high-energy foods and caloric overload are implicated in the dysfunction of the blood‒brain barrier (BBB), cognitive impairment, and overactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes hydrolyse acetylcholine, affecting anti-inflammatory cholinergic signalling. Our aim was to evaluate whether nicotinamide (NAM) attenuates the impairment of the BBB and cognitive function, improving cholinergic signalling. Forty male rats were distributed into five groups: one group was fed a standard diet, and the remaining groups were fed a high-fat diet and a beverage with 40% sucrose (HFS; high-fat sucrose). In three of the HFS groups, the carbohydrate was replaced by drinking water containing different concentrations of NAM for 5 h every morning for 12 weeks. The biochemical profile, levels of stress and inflammation markers, cholinesterase activities, BBB permeability, and cognitive capacity were evaluated. The results showed that the HFS diet disturbed the metabolism of carbohydrates and lipids, causing insulin resistance. Simultaneously, AChE and BChE activities, levels of proinflammatory cytokines, oxidation of proteins and lipoperoxidation increased along with decreased antioxidant capacity in serum. In the hippocampus, increased activity of cholinesterases, protein carbonylation and lipoperoxidation were associated with decreased antioxidant capacity. Systemic and hippocampal changes were reflected in increased BBB permeability and cognitive impairment. In contrast, NAM attenuated the above changes by reducing oxidative stress and inflammation through decreasing cholinesterase activities, especially by uncompetitive inhibition. NAM may be a potential systemic and neuroprotective agent to mitigate cognitive damage due to hypercaloric diets.

Percepciones de los estudiantes sobre sus vivencias en las prácticas clínicas / Students' perceptions about their experiences in their clinical practices / Percepciones dos estudantes sobre suas vivências nas práticas clínicas

Resumen Introducción Los estudiantes de enfermería deben adquirir conocimientos, habilidades, actitudes y valores, para proporcionar cuidados de calidad. Las prácticas clínicas son el contexto ideal para lograr algunas de las competencias requeridas. Objetivo Explorar las percepciones de los estudiantes sobre sus vivencias durante sus prácticas clínicas. Método Abordaje metodológico descriptivo de tipo cualitativo y con un encuadre sociocrítico. Se analizaron los 45 portafolios de estudiantes de 4º curso de la Escuela Universitaria de Enfermería (EUE) Cruz Roja, donde explican sus vivencias en prácticas. Se optó por un portafolio semiestructurado en función de la competencia a demostrar definiendo previamente las tareas o evidencias Se realizó un análisis de contenido que comprendía las siguientes fases: reducción de los datos; categorización-codificación, presentación de datos y conclusiones/verificación de los datos. Se alcanzó saturación en la información sobre las categorías presentadas. Resultados Del análisis de los datos emergen distintas unidades de significado que se engloban en tres categorías: aprendizaje en prácticas, dificultades del entorno, crecimiento personal y profesional. Conclusiones El estudio evidencia la importancia de las prácticas clínicas para los estudiantes dentro del plan de estudios, ya que es donde aplican lo que han aprendido en el aula y son conscientes de la realidad a la que se enfrentan. El entorno clínico y la relación que se establezca entre este y el estudiante determina en muchas ocasiones el aprendizaje. Queda patente que los estudiantes durante sus prácticas clínicas toman conciencia de aquellos conocimientos del saber, saber hacer y saber estar.

Abstract Introduction Nursing students need specific knowledge, skills, attitudes and values in order to provide quality of care; and the clinical practices represent an ideal context to develop some of these required competences. Objective To explore the perceptions of nursing students about their own experiences in their clinical practices. Method This a qualitative descriptive study with social and critical focus. 45 practice-files from nursing students in the 4th course of a Mexico Red Cross School of Nursing were analyzed considering the following stages: data reduction, categorization-coding, data presentation, and data verification and conclusions. Data saturation was reached from the identified categories. Results From the data analysis, diverse units of meaning emerged within three main categories: learning in practices, difficulties in the environment, and personal and professional growth. Conclusions The study highlights the importance of clinical practices since it is there where students apply in real life what they learn in the classroom. The relationship between the student and the clinical environment greatly determines the quality of learning. So, it is suggested that students keep in mind reflecting on their to know, to know how, and to know how to be.

Resumo Introdução Os estudantes de enfermagem devem adquirir conhecimentos, habilidades, atitudes e valores, para proporcionar cuidados de qualidade. As práticas clínicas são o contexto ideal para atingir algumas das competências requeridas. Objetivo Explorar as percepções dos estudantes sobre suas vivências durante suas práticas clínicas. Método Abordagem metodológica descritiva de tipo qualitativo e com um enfoque sociocrítico. Analisaram-se os 45 portfolios de estudantes de 4º curso da Escuela Universitaria de Enfermería (EUE) Cruz Roja, onde explicam suas vivências em práticas. Optou-se por um portfólio semiestruturado em função da competência a demostrar definindo previamente as tarefas ou evidências. Realizou-se uma análise de conteúdo que compreendia as seguintes fases: redução dos dados; categorização-codificação, apresentação de dados e conclusões/verificação dos dados. Atingiu-se saturação na informação sobre as categorias apresentadas. Resultados Da análise dos dados emergem distintas unidades de significado que abrangem três categorias: aprendizagem em práticas, dificuldades do entorno, crescimento pessoal e profissional. Conclusões O estudo evidencia a importância das práticas clínicas para os estudantes dentro do plano de estudos, já que é onde aplicam o que aprenderam na aula e são conscientes da realidade à que se enfrentam. O entorno clínico e a relação que se estabeleça entre este e o estudante determina em muitas ocasiões a aprendizagem. É evidente que os estudantes durante suas práticas clínicas tomam consciência daqueles conhecimentos do saber, saber fazer e saber estar.

Biological effects of silk fibroin 3D scaffolds on stem cells from human exfoliated deciduous teeth (SHEDs).

The aim is to investigate in vitro biological effects of silk fibroin 3D scaffolds on stem cells from human exfoliated deciduous teeth (SHEDs) in terms of proliferation, morphological appearance, cell viability, and expression of mesenchymal stem cell markers. Silk fibroin 3D scaffolding materials may represent promising suitable scaffolds for their application in regenerative endodontic therapy approaches. SHEDs were cultured in silk fibroin 3D scaffolds. Then, cell numbers were counted and the Alamar blue colorimetric assay was used to analyse cell proliferation after 24, 48, 72, and 168 h of culture. The morphological features of SHEDs cultured on silk fibroin scaffolds were evaluated by scanning electron microscopy (SEM). Finally, cell viability and the expression of mesenchymal stem cell markers were analysed by flow cytometry. One-way analysis of variance (ANOVA) followed by a Bonferroni post-test was performed (P < 0.05). At 24 and 48 h of culture, SHED proliferation on scaffolds was modest compared to the control although still significant (p < 0.05). However, cell proliferation progressively increased from 72 to 168 h compared with the control (p < 0.001; p < 0.01). In addition, flow cytometry analysis showed that the culture of SHEDs on silk fibroin scaffolds did not significantly alter the level of expression of the mesenchymal markers CD73, CD90, or CD105 up to 168 h; in addition, cell viability in silk fibroin was similar to than obtained in plastic. Moreover, SEM studies revealed a suitable degree of proliferation, cell spreading, and attachment, especially after 168 h of culture. The findings from the current study suggest that silk fibroin 3D scaffolds had a favourable effect on the biological responses of SHEDs. Further in vivo investigations are required to confirm these results.

Effect of aqueous and particulate silk fibroin in a rat model of experimental colitis.

Silk fibroin (SF) has anti-inflammatory properties and promotes wound healing. Moreover, SF particles act as carriers of active drugs against intestinal inflammation due to their capacity to deliver the compound to the damaged colonic tissue. The present work assesses the effect of SF in the trinitrobenzenesulfonic acid model of rat colitis that resembles human intestinal inflammation. SF (8mg/kg) was administered in aqueous solution orally and in two particulate formats by intrarectal route, following two technologies: spray drying to make microparticles and desolvation in organic solvent to produce nanoparticles. SF treatments ameliorated the colonic damage, reduced neutrophil infiltration and improved the compromised oxidative status of the colon. They also reduced the gene expression of pro-inflammatory cytokines like IL-1ß and the anti-inflammatory cytokine IL-10. Moreover, they improved the intestinal wall integrity by increasing the gene expression of some of its markers (villin, trefoil factor-3 and mucins), thus accelerating the healing. The immunomodulatory properties of SF particles were also tested in vitro in macrophages: they activated the immune response in basal conditions without increasing it after a pro-inflammatory insult. In conclusion, SF particles could be useful as carriers to deliver active drugs to the damaged intestinal colon with additional anti-inflammatory and healing properties.

Wnt9a deficiency discloses a repressive role of Tcf7l2 on endocrine differentiation in the embryonic pancreas.

Transcriptional and signaling networks establish complex cross-regulatory interactions that drive cellular differentiation during development. Using microarrays we identified the gene encoding the ligand Wnt9a as a candidate target of Neurogenin3, a basic helix-loop-helix transcription factor that functions as a master regulator of pancreatic endocrine differentiation. Here we show that Wnt9a is expressed in the embryonic pancreas and that its deficiency enhances activation of the endocrine transcriptional program and increases the number of endocrine cells at birth. We identify the gene encoding the endocrine transcription factor Nkx2-2 as one of the most upregulated genes in Wnt9a-ablated pancreases and associate its activation to reduced expression of the Wnt effector Tcf7l2. Accordingly, in vitro studies confirm that Tcf7l2 represses activation of Nkx2-2 by Neurogenin3 and inhibits Nkx2-2 expression in differentiated ß-cells. Further, we report that Tcf7l2 protein levels decline upon initiation of endocrine differentiation in vivo, disclosing the downregulation of this factor in the developing endocrine compartment. These findings highlight the notion that modulation of signalling cues by lineage-promoting factors is pivotal for controlling differentiation programs.

Effects of composite films of silk fibroin and graphene oxide on the proliferation, cell viability and mesenchymal phenotype of periodontal ligament stem cells.

In regenerative dentistry, stem cell-based therapy often requires a scaffold to deliver cells and/or growth factors to the injured site. Graphene oxide (GO) and silk fibroin (SF) are promising biomaterials for tissue engineering as they are both non toxic and promote cell proliferation. On the other hand, periodontal ligament stem cells (PDLSCs) are mesenchymal stem cells readily accessible with a promising use in cell therapy. The purpose of this study was to investigate the effects of composite films of GO, SF and GO combined with fibroin in the mesenchymal phenotype, viability, adhesion and proliferation rate of PDLSCs. PDLSCs obtained from healthy extracted teeth were cultured on GO, SF or combination of GO and SF films up to 10 days. Adhesion level of PDSCs on the different biomaterials were evaluated after 12 h of culture, whereas proliferation rate of cells was assessed using the MTT assay. Level of apoptosis was determined using Annexin-V and 7-AAD and mesenchymal markers expression of PDLSCs were analyzed by flow cytometry. At day 7 of culture, MTT experiments showed a high rate of proliferation of PDLSCs growing on GO films compared to the other tested biomaterials, although it was slightly lower than in plastic (control). However PDLSCs growing in fibroin or GO plus fibroin films showed a discrete proliferation. Importantly, at day 10 of culture it was observed a significant increase in PDLSCs proliferation rate in GO films compared to plastic (P < 0.05), as well as in GO plus fibroin compared to fibroin alone (P < 0.001). Flow cytometry analysis showed that culture of PDLSCs in fibroin, GO or GO plus fibroin films did not significantly alter the level of expression of the mesenchymal markers CD73, CD90 or CD105 up to 168 h, being the cell viability in GO even better than obtained in plastic. Our findings suggest that the combination of human dental stem cells/fibroin/GO based-bioengineered constructs have strong potential for their therapeutic use in regenerative dentistry.

Endovascular treatment of type B dissection in patients with Marfan syndrome: mid-term outcomes and aortic remodeling.

OBJECTIVES: To evaluate the mid-term outcomes, and the aortic remodeling in Marfan syndrome (MFS) patients with type B dissection that were treated with endovascular repair. BACKGROUND: MFS is a relative contraindication to thoracic endovascular aortic repair (TEVAR). Mid-term aortic outcomes data in MFS after TEVAR are limited, and the occurrence of late events remains unclear. METHODS: Of 89 patients that underwent TEVAR between September 2002 and February 2011, 10 patients with mid-term follow-up fulfilled the Ghent criteria for MFS and complicated type B dissection. High risk for open surgery was documented in 90%. RESULTS: The mean age was 35.1 ± 9.4 years and all patients presented with acute aortic syndrome complicating a chronic type B dissection (DeBakey type IIIb). Five patients underwent a Bentall surgical procedure previous to endovascular repair, and in four patients initial TEVAR was followed by surgery of the ascending aorta. Treatment was limited to endovascular repair in only one patient. In-hospital mortality was 10%. At a mean follow-up of 59.6 ± 38.9 months, the cumulated mortality was of 20% and late mortality 11.1%. The rate of secondary endoleak was 44.4%, and late reintervention of 33.3%. Survival freedom from cardiovascular death at 8 years was 80.0%, and positive remodeling was documented in 37.5% of patients. CONCLUSIONS: Our results suggest that TEVAR is feasible, safe, and associated with a high reintervention rate and reduced rate of positive aortic remodeling in patients with Marfan syndrome. Survival at 8 years was comparable to contemporary series of open repair.

Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer's disease.

Aside from APOE, the genetic factors that influence the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) remain largely unknown. We assessed whether a genetic risk score (GRS), based on eight non-APOE genetic variants previously associated with AD risk in genome-wide association studies, is associated with either risk of conversion or with rapid progression from MCI to AD. Among 288 subjects with MCI, follow-up (mean 26.3 months) identified 118 MCI-converters to AD and 170 MCI-nonconverters. We genotyped ABCA7 rs3764650, BIN1 rs744373, CD2AP rs9296559, CLU rs1113600, CR1 rs1408077, MS4A4E rs670139, MS4A6A rs610932, and PICALM rs3851179. For each subject we calculated a cumulative GRS, defined as the number of risk alleles (range 0-16) with each allele weighted by the AD risk odds ratio. GRS was not associated with risk of conversion from MCI to AD. However, MCI-converters to AD harboring six or more risk alleles (second and third GRS tertiles) progressed twofold more rapidly to AD when compared with those with less than six risk alleles (first GRS tertile). Our GRS is a first step toward development of prediction models for conversion from MCI to AD that incorporate aggregate genetic factors.

Lack of association of LINGO1 rs9652490 and rs11856808 SNPs with familial essential tremor.

BACKGROUND: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. METHODS: We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. RESULTS: We were unable to replicate the association between LINGO1 variants and familial ET. CONCLUSIONS: Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population.

Homodimerization of presenilin N-terminal fragments is affected by mutations linked to Alzheimer's disease.

Mutations on human presenilins 1 and 2 cause dominant early-onset familial Alzheimer's disease (FAD). Presenilins are polytopic transmembrane proteins endoproteolytically processed in vivo to N- and C-terminal fragments (NTFs and CTFs). The functional presenilin unit consists of a high molecular weight complex that contains both fragments. Here we show NTF:NTF, CTF:CTF and NTF:CTF interactions by yeast two-hybrid and in vivo endoplasmic reticulum split-ubiquitin assays. Our results also highlight the involvement of HL1--the hydrophilic loop between TMI and TMII--in the NTF:NTF binding site. Besides, nine FAD-linked presenilin mutations substantially affected HL1:HL1 binding. From the evidence of NTF and CTF homodimerization, we propose the contribution of two NTFs and two CTFs, instead of a single NTF:CTF heterodimer, to the functional presenilin-gamma-secretase complex and that FAD mutations affect the assembly or stability of this complex.

Complex brain circuits studied via simultaneous and permanent detection of three transported neuroanatomical tracers in the same histological section.

Experimental neuroanatomical tracing methods lie at the basis of the study of the nervous system. When the scientific question is relatively straightforward, it may be sufficient to derive satisfactory answers from experiments in which a single neuroanatomical tracing method is applied. In various scientific paradigms however, for instance when the degree of convergence of two different projections on a particular cortical area or subcortical nucleus is the subject of study, the application of single tracing methods can be either insufficient or uneconomical to solve the questions asked. In cases where chains of projections are the subjects of study, the simultaneous application of two tracing methods or even more may be compulsory. The present contribution focuses on combinations of several neuroanatomical tract-tracing strategies, enabling in the end the simultaneous, unambiguous and permanent detection of three transported markers according to a three-color paradigm. A number of combinations of three tracers or of two tracers plus the immunocytochemical detection of a neuroactive substance can be conceived; we describe several of these combinations implemented by us using the present multitracer protocol.

Determinants of the evolution of the health situation of the population.

The objective of the present project is to evaluate the relative importance of different governmental social programmes for health development during the 1970's. National statistics available for the whole period and disaggregated to district level were analyzed with particular regard to three indicators of infant health status when the infant mortality rate was used, increased access to secondary care and improved socio-economic status were related to improvement in infant health status. When the percentage of neonatal deaths or the percentage of deceased live births per woman was used, neither the socio-economic improvement nor the assess to secondary did explain the improvement. Moreover, the primary health programme did not seem to be of importance in explaining the changes in the three indicators of infant health status. A second phase of the project, currently ongoing, is aimed at the evaluation of other factors such as the degree of efficiency of some of the health programmes. This study is based on directly collected information, quantitative as well as qualitative. Structured interviews have been used together with anthropological information from in-depth interviews with individuals and groups. The preliminary results of this second phase indicate that the contradictions observed in the first phase might be due to shortcomings in the national registers. In one of the study areas the coverage of PHC developed earlier than indicated by the official information. In other areas it was found that different obstacles as access problems, lack of health centers, socio-economical problems and lack of cultural knowledge reduced the effectiveness and impact of the primary health programmes.

PIP: Costa rica has achieved considerable success in social development and attention to the marginalized poor. The aim of this study is to assess the impact of health and nutrition from social interventions of the 1970s and to provide an explanation. Archival data on vital statistics from 1970 to 1984 and coverage of the Rural Health and Community Health Programs were used. In general, data were analyzed on the district level and in zones where population was sparse. Dependent variables were infant mortality under 1 year/live births, neonatal deaths 1-11 months/infant mortality, and mortality of live births/live births of women 20-24 years. Independent variables were health coverage, access to medical assistance, environmental conditions, educational status, rural residence, and the presence of modern living conditions. The results showed that major changes occurred in access to different health programs in rural and backward regions. National coverage was 60% in 1978. In 1980, 70% were covered by social security and 95% of all deliveries were medically assisted by trained health personnel. Electricity, water, and sanitation also improved. Independent variables were closely and inversely related to infant mortality around 1974 and declined in effect about 1983. Socioeconomic factors and access to health care became else important. There was less geographic variation in infant mortality. The percentage of postneonatal mortality and the percentage of live birth deaths continued to be strongly associated by the end of the period (1983). Correlation coefficients were generated for the absolute changes in the 2 measures of infant mortality for the time periods: 1973-75, 1976-78, and 1979-81. The results were all highly significant. Regions with low socioeconomic development and low access to health care and regions with high primary health care (PHC) had greater reductions in infant mortality. When the analysis was repeated with changes in independent variables, infant, mortality was reduced in regions with increases in secondary health programs, larger PHC coverage, and greater increases in standard of living measures. In a socioanthropological approach in 1988, preliminary results continued to show inconsistencies in the 3 infant mortality measures. Data deficiencies are suspected to be the cause and analysis is ongoing to correct for doubtful figures.

Evolucion de la talla 1979-1981 Costa Rica. / Evolution of body height 1979-1981. Costa Rica

Se presenta los datos comparados de los censos de talla a escolares de primer grado de 1979 y 1981. Se observa como entre los ninos de 7 anos de la cohorte nacida en 1972 y de la cohorte nacida en 1974 ha habido una ganancia en la talla del orden de los 2.5 cms. Asimismo se presentan las diferencias de talla existentes entre ninos costarricenses sean estos que asisten a escuelas publicas o privadas