Hypothalamic inflammation and the development of an obese phenotype induced by high-fat diet consumption is exacerbated in alpha7 nicotinic cholinergic receptor knockout mice.

Hypothalamic inflammation and metabolic changes resulting from the consumption of high-fat diets have been linked to low grade inflammation and obesity. Inflammation impairs the hypothalamic expression of α7 nicotinic acetylcholine receptor (α7nAChR). The α7nAChR is described as the main component of the anti-inflammatory cholinergic pathway in different inflammation models. To assess whether the reduction in α7nAChR expression exacerbates hypothalamic inflammation induced by a high-fat diet (HFD), were used male and female global α7nAChR knockout mouse line in normal or high-fat diet for 4 weeks. Body weight gain, adiposity, glucose homeostasis, hypothalamic inflammation, food intake, and energy expenditure were evaluated. Insulin sensitivity was evaluated in neuronal cell culture. Consumption of an HFD for 4 weeks resulted in body weight gain and adiposity in male Chrna7-/- mice and the hypothalamus of male Chrna7-/- mice showed neuroinflammatory markers, with increased gene expression of pro-inflammatory cytokines and dysregulation in the nuclear factor kappa B pathway. Moreover, male Chrna7-/- mice consuming an HFD showed alterations in glucose homeostasis and serum of Chrna7-/- mice that consumed an HFD impaired insulin signalling in neuronal cell culture experiments. In general, female Chrna7-/- mice that consumed an HFD did not show the phenotypic and molecular changes found in male mice, indicating that there is sexual dimorphism in the analysed parameters. Thus, receptor deletion resulted in increased susceptibility to hypothalamic inflammation and metabolic damage associated with HFD consumption in male mice.

Extraocular muscle stem cells exhibit distinct cellular properties associated with non-muscle molecular signatures.

Skeletal muscle stem cells (MuSCs) are recognised as functionally heterogeneous. Cranial MuSCs are reported to have greater proliferative and regenerative capacity when compared with those in the limb. A comprehensive understanding of the mechanisms underlying this functional heterogeneity is lacking. Here, we have used clonal analysis, live imaging and single cell transcriptomic analysis to identify crucial features that distinguish extraocular muscle (EOM) from limb muscle stem cell populations. A MyogeninntdTom reporter showed that the increased proliferation capacity of EOM MuSCs correlates with deferred differentiation and lower expression of the myogenic commitment gene Myod. Unexpectedly, EOM MuSCs activated in vitro expressed a large array of extracellular matrix components typical of mesenchymal non-muscle cells. Computational analysis underscored a distinct co-regulatory module, which is absent in limb MuSCs, as driver of these features. The EOM transcription factor network, with Foxc1 as key player, appears to be hardwired to EOM identity as it persists during growth, disease and in vitro after several passages. Our findings shed light on how high-performing MuSCs regulate myogenic commitment by remodelling their local environment and adopting properties not generally associated with myogenic cells.

The synergistic effects of soil-applied boron and foliar-applied silicon on cotton fiber quality and yield.

Studies of boron (B) and silicon (Si) synergy in cotton crops have shown promising results; however, the focus was on the foliar application of B and Si. Nonetheless, B is an element with little mobility in the plant and its best form of application is in the soil. Thus, the objective of this study was to evaluate the synergistic effect of soil applied B and foliar applied sSi on fiber quality and crop yield of cotton. For this purpose, a field experiment was carried out using cotton cultivar FM 985 GLTP. The soil's B in the experimental site is classified as low for cotton cultivation. The experiment was conducted in a randomized complete-block design, in a 3 × 2 factorial scheme, with three doses of B: 0.0 kg ha-1 (deficiency), 2.0 kg ha-1 (recommended dose), and 4.0 kg ha-1 (high dose) in the absence and presence (920 g L-1) of Si, with four replications. One week after the 4th application of Si, B and Si leaf content was determined. At boll opening, crop yield was estimated, and fiber quality analysis was realized. Boron deficiency reduced cotton yield, in 11 and 9%, compared to the application of 2 and 4 kg ha-1 of B, respectively. The presence of Si, however, increased plant yield in 5% in the treatments with 0 and 2 kg ha-1 of B, respectively. Cotton fiber length and elongation were not influenced by the B doses and Si presence. Fiber breaking strength was increased in 5% by the presence of Si and was not influenced by B deficiency. Micronaire was 8% smaller in the treatment with 0 kg ha-1 of B and 6% smaller in the absence of Si. Short fiber index was 4% greater in the plants of the treatment with 0 kg ha-1 of B. The results of this study reports that the complementation with Si via foliar application increases fiber quality by enhance breaking strength and micronaire. In conclusion, the interaction between soil-applied B and foliar-applied Si is beneficial for cotton cultivation, resulting in high cotton yield with better fiber quality.

Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.

The α7nAChR is crucial to the anti-inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short-term exposure to an obesogenic diet. Bioinformatic analysis revealed Let-7 microRNAs as candidates to regulate Chrna7, which was confirmed by the luciferase assay. Mice exposed to an obesogenic diet for 3 days had increased Let-7a and decreased α7nAChR levels, accompanied by hypothalamic fatty acids and TNFα content. Hypothalamic neuronal cells exposed to fatty acids presented higher Let-7a and TNFα levels and lower Chrna7 expression, but when the cells were pre-treated with TLR4 inhibitor, Let-7a, TNFα, and Chrna7 were rescued to normal levels. Thus, the fatty acids overload trigger TNFα-induced Let-7 overexpression in hypothalamic neuronal cells, which negatively regulates α7nAChR, an event that can be related to hyperphagia and obesity predisposition in mice.

Maternal consumption of a high-fat diet modulates the inflammatory response in their offspring, mediated by the M1 muscarinic receptor.

Introduction: High-fat diet (HFD) consumption is associated with various metabolic disorders and diseases. Both pre-pregnancy and maternal obesity can have long-term consequences on offspring health. Furthermore, consuming an HFD in adulthood significantly increases the risk of obesity and metabolic disorders. However, an intriguing phenomenon known as the obesity paradox suggests that obesity may confer a protective effect on mortality outcomes in sepsis. In sepsis, activation of the cholinergic anti-inflammatory pathway (CAP) can help mitigate systemic inflammation. We employed a metabolic programming model to explore the relationship between maternal HFD consumption and offspring response to sepsis. Methods: We fed female mice either a standard diet (SC) or an HFD during the pre-pregnancy, pregnancy, and lactation periods. Subsequently, we evaluated 28-day-old male offspring. Results: Notably, we discovered that offspring from HFD-fed dams (HFD-O) exhibited a higher survival rate compared with offspring from SC-fed dams (SC-O). Importantly, inhibition of the m1 muscarinic acetylcholine receptor (m1mAChR), involved in the CAP, in the hypothalamus abolished this protection. The expression of m1mAChR in the hypothalamus was higher in HFD-O at different ages, peaking on day 28. Treatment with an m1mAChR agonist could modulate the inflammatory response in peripheral tissues. Specifically, CAP activation was greater in the liver of HFD-O following agonist treatment. Interestingly, lipopolysaccharide (LPS) challenge failed to induce a more inflammatory state in HFD-O, in contrast to SC-O, and agonist treatment had no additional effect. Analysis of spleen immune cells revealed a distinct phenotype in HFD-O, characterized by elevated levels of CD4+ lymphocytes rather than CD8+ lymphocytes. Moreover, basal Il17 messenger RNA (mRNA) levels were lower while Il22 mRNA levels were higher in HFD-O, and we observed the same pattern after LPS challenge. Discussion: Further examination of myeloid cells isolated from bone marrow and allowed to differentiate showed that HFD-O macrophages displayed an anti-inflammatory phenotype. Additionally, treatment with the m1mAChR agonist contributed to reducing inflammatory marker levels in both groups. In summary, our findings demonstrate that HFD-O are protected against LPS-induced sepsis, and this protection is mediated by the central m1mAChR. Moreover, the inflammatory response in the liver, spleen, and bone marrow-differentiated macrophages is diminished. However, more extensive analysis is necessary to elucidate the specific mechanisms by which m1mAChR modulates the immune response during sepsis.

Behavioral, neuroplasticity and metabolic effects of 7,8-dihydroxy-4-methylcoumarin associated with physical activity in mice.

The search for strategies to develop resilience against metabolic and neuropsychiatric disorders has motivated the clinical and experimental assessment of early life interventions such as lifestyle-based and use of unconventional pharmacological compounds. In this study, we assessed the effects of voluntary physical activity and 7,8-Dihydroxy-4-methylcoumarin (DHMC), independently or in combination, over mice physiological and behavioral parameters, adult hippocampal and hypothalamic neurogenesis, and neurotrophic factors expression in the hypothalamus. C57Bl/6J mice were submitted to a 29-day treatment with DHMC and allowed free access to a running wheel. We found that DHMC treatment alone reduced fasting blood glucose levels. Moreover, physical activity showed an anxiolytic effect in the elevated plus maze task and DHMC produced additional anxiolytic behavior, evidenced by reduced activity during the light cycle in the physical activity group. Although we did not find any differences in hypothalamic or hippocampal adult neurogenesis, DHMC increased gene expression levels of VEGF, which was correlated to the reduced fasting glucose levels. In conclusion, our data emphasize the potential of physical activity in reducing development of neuropsychiatric conditions, such as anxiety, and highlights DHMC as an attractive compound to be investigated in future studies addressing neuropsychiatric disorders associated with metabolic conditions.

High-throughput screening identifies suppressors of mitochondrial fragmentation in OPA1 fibroblasts.

Mutations in OPA1 cause autosomal dominant optic atrophy (DOA) as well as DOA+, a phenotype characterized by more severe neurological deficits. OPA1 deficiency causes mitochondrial fragmentation and also disrupts cristae, respiration, mitochondrial DNA (mtDNA) maintenance, and cell viability. It has not yet been established whether phenotypic severity can be modulated by genetic modifiers of OPA1. We screened the entire known mitochondrial proteome (1,531 genes) to identify genes that control mitochondrial morphology using a first-in-kind imaging pipeline. We identified 145 known and novel candidate genes whose depletion promoted elongation or fragmentation of the mitochondrial network in control fibroblasts and 91 in DOA+ patient fibroblasts that prevented mitochondrial fragmentation, including phosphatidyl glycerophosphate synthase (PGS1). PGS1 depletion reduces CL content in mitochondria and rebalances mitochondrial dynamics in OPA1-deficient fibroblasts by inhibiting mitochondrial fission, which improves defective respiration, but does not rescue mtDNA depletion, cristae dysmorphology, or apoptotic sensitivity. Our data reveal that the multifaceted roles of OPA1 in mitochondria can be functionally uncoupled by modulating mitochondrial lipid metabolism, providing novel insights into the cellular relevance of mitochondrial fragmentation.

Schistosoma mansoni: In vitro schistosomicidal activity of piplartine.

Schistosomiasis is one of the world's greatly neglected tropical diseases, and its control is largely dependent on a single drug, praziquantel. Here, we report the in vitro effect of piplartine, an amide isolated from Piper tuberculatum (Piperaceae), on Schistosoma mansoni adult worms. A piplartine concentration of 15.8 µM reduced the motor activity of worms and caused their death within 24h in a RPMI 1640 medium. Similarly, the highest sub-lethal concentration of piplartine (6.3 µM) caused a 75% reduction in egg production in spite of coupling. Additionally, piplartine induced morphological changes on the tegument, and a quantitative analysis carried out by confocal microscopy revealed an extensive tegumental destruction and damage in the tubercles. This damage was dose-dependent in the range of 15.8-630.2 µM. At doses higher than 157.6 µM, piplartine induced morphological changes in the oral and ventral sucker regions of the worms. It is the first time that the schistosomicidal activity has been reported for piplartine.

Percepções de acadêmicos de enfermagem sobre finitude em instituições hospitalares / Perceptions from undergraduate nursing students about finitude in hospitals / Percepciones de estudiantes de enfermería de proceso finitud en hospitales

Objetivo: compreender o processo da morte e do morrer nos hospitais na percepção de acadêmicos de enfermagem. Metodologia: estudo qualitativo, de abordagem fenomenológica, com sete graduandos de enfermagem da Universidade José Rosário Vellano. O Projeto de Pesquisa que foi aprovado pelo parecer n°. 76/2009 do Comitê de Ética da referida Universidade. Resultados: a análise das falas possibilitou a elaboração de cinco categorias: 1) Pensando na morte, vivenciando a angústia; 2) Profissionalismo na visão dos acadêmicos e o envolvimento com os casos; 3) O impacto psicológico no momento da perda; 4) A importância da assistência à família do paciente; 5) Compreendendo a necessidade de discutir a morte na formação acadêmica. Conclusão: os resultados evidenciaram que os acadêmicos se sentem despreparados para lidar com a morte, demonstrando uma certa angústia, insegurança ao falar sobre o assunto, isso se deve ao fato da discussão dessa temática não ser freqüente dentro da graduação, entendemos que a criação de espaços para autoconhecimento, sensibilização e reflexão sobre o tema morte nas universidades, possibilitaria a formação de profissionais não só capacitados para assistir a vida visando a reabilitação ou a cura, mas também preparados para lidar com a morte. (AU)

Objective: understanding the process of death and dying in hospitals in the perception of undergraduate nursing students. Methodology: this is about a qualitative study, from phenomenological approach, performed of seven nursing students at the University José Rosário Vellano. The research project has been approved by the Ethics Committee in Research of the University José Rosário Vellano (protocol number 76/2009). Results: through the interviews was enabled the construction of five categories: 1) Thinking about death, experiencing anxiety, 2) Professionalism in the view of academics and involvement with the cases, 3) The psychological impact at the time of loss and 4) The importance of family care of the patient; 5) Understanding the need to discuss death in academic education. Conclusion: the results showed that the students feel unprepared to deal with death, demonstrating a degree of anxiety, insecurity to talk about it, this is because the discussion of this issue is not frequent in the graduation, we believe that the creation of spaces for selfknowledge, awareness and reflection on the theme of death in the universities, would allow the training of professionals not only able to watch life for the rehabilitation or cure, but also prepared to deal with death. (AU)

Objetivo: comprender el proceso de morir y la muerte en los hospitales de la percepción de estudiantes de enfermería. Metodología: estudio cualitativo, de enfoque fenomenológico. Participaron en el estudio, siete estudiantes de enfermería de la Universidad José Rosario Vellano después que lo proyecto de investigación fue aprobado por el Comité de Ética (número del registro 76/2009). Resultados: el análisis de las declaraciones permitieron la construcción de cinco categorías: 1) Pensar en la muerte, experimentan ansiedad, 2) La profesionalidad en el punto de vista de los académicos y la participación de los casos, 3) El impacto psicológico en el momento de la pérdida de y 4) La importancia de la atención de la familia del paciente, 5) Comprender la necesidad de hablar de la muerte en la educación académica. Conclusión: Los resultados mostraron que los estudiantes no se sienten preparados para enfrentar la muerte, lo que demuestra un grado de ansiedad, inseguridad para hablar de ello, esto no es porque la discusión de este tema es frecuente en la graduación, creemos que la creación de espacios de auto-conocimiento, conciencia y reflexión sobre el tema de la muerte en las universidades, que permitiría la formación de profesionales no sólo es capaz de ver la vida para la rehabilitación o cura, sino también preparados para lidiar con la muerte.(AU)

Uso de dentifrício fluoretado e hábitos de escovação em crianças de 6 a 36 meses de idade / Use of fluoride dentifrice and toothbrushing habits in children aged 6 to 36 months

Objetivo: Este estudo avaliou o uso de dentifrício fluoretado e os hábitos de escovação de crianças de 6 a 36 meses de idade assistidas por um programa preventivo (Bebê Clínica). Material e Método: A coleta dos dados foi realizada por meio de entrevista com os pais utilizando um questionário estruturado contendo perguntas referentes à criança e aos hábitos de escovação. Os dados coletados foram tabulados e submetidos à análise estatística. Resultados: Foram respondidos 126 questionários. Foi possível constatar que 98 (77,78%) crianças usavam dentifrício fluoretado e haviam iniciado o seu uso, em média, aos 13,5 meses, sendo que 34,70% usavam o dentifrício convencional e 65,3% o infantil. Destas, 41,84% e 39,80% utilizavam, respectivamente, uma quantidade mínima e uma pequena quantidade. 99,21% das crianças utilizavam escova infantil. Apenas 5,1% escovavam uma vez ao dia, 43,88%, 42,86% e 7,14% escovavam duas, três e quatro vezes ao dia, respectivamente. Foi verificado que 94,9% das crianças escovavam os dentes sob supervisão dos pais, 74,49% bochechavam com água, 64,29% cuspiam e 83,67% engoliam o dentifrício durante e/ou após a escovação. Conclusão: Com base na metodologia utilizada, concluiu-se que as crianças iniciaram a escovação com dentifrício fluoretado muito precocemente.

Aim: This study evaluated the use of fluoride toothpaste and toothbrushing habits of children aged 6-36 months assisted by a preventive program (Clinic Babies). Material and Method: A questionnaire was administered o the parents/guardians for data collection regarding of children and toothbrushing habits. Data obtained were analyzed by statistical techniques. 126 questionaires were answered. 77.78% children used fluoride dentifrice. The mean age that children began toothbrushing was 13.5 months and 99.21% used infantile toothbrush. 34.70% used conventional dentifrice and 65.3% used children's dentifrice. 41.84% and 39.80% used, respectively, minimal amount and small amount of dentifrice. Only 5.1% of children had their tooth brushed once a day and 43.88%, 42.82% and 7.14% 2, 3 and 4 times a day, respectively. 94.9% were supervised by an adult, 74.49% rinsed with water and 83.67% ingested fluoride dentifrice during and/or after toothbrushing. Conclusion: Based on the methodology used, it was possible to conclude that children began the toothbrushing with fluoride dentifrice very early.

Utilização do laser em bolsas periodontais revisão de literatura / Laser Utilization in Periodontal Pockets

O uso do laser tem sido avaliado tanto durante a raspagem e alisamento radicular, quanto como substituto de antimicrobianos sistêmicos na desinfecção de bolsas periodontais. Os estudos a respeito deste assunto são recentes, datando a partir da década de 90. Os lasers de baixa intensidade atuam como coadjuvantes à terapia periodontal. e trazem benefícios valiosos à mesma, como diminuição da hiperestesia dentinária e cura mais rápida dos teddos após raspagem. Quanto aos lasers de alta intensidade, é questionável sua eficácia no debridamento radicular sem que cause possíveis efeitos térmicos danosos à estrutura dentária. Este trabalho aborda a utilização do laser em bolsas periodontais e suas possíveis conseqüências