Cutin-Derived Oligomers Induce Hallmark Plant Immune Responses.

The cuticle constitutes the outermost defensive barrier of most land plants. It comprises a polymeric matrix - cutin, surrounded by soluble waxes. Moreover, the cuticle constitutes the first line of defense against pathogen invasion, while also protecting the plant from many abiotic stresses. Aliphatic monomers in cutin have been suggested to act as immune elicitors in plants. This study analyses the potential of cutin oligomers to activate rapid signaling outputs reminiscent of pattern-triggered immunity (PTI) in the model plant Arabidopsis. Cutin oligomeric mixtures led to Ca2+ influx and MAPK activation. Comparable responses were measured for cutin, which was also able to induce a reactive oxygen species (ROS) burst. Furthermore, cutin oligomer treatment resulted in a unique transcriptional reprogramming profile, having many archetypal features of PTI. Targeted spectroscopic and spectrometric analyses of the cutin oligomers suggest that the elicitors compounds consist mostly of two up to three 10,16-dihydroxyhexadecanoic acid monomers linked together through ester bonds. This study demonstrates that cutin breakdown products can act as inducers of early plant immune responses, which underlying mechanisms of perception and potential use in agriculture warrant further investigation.

Characterization and quantification of epilepsy patients with hospital episodes in Portugal: A multicenter retrospective study from Liga Portuguesa Contra a Epilepsia.

INTRODUCTION: Epilepsy affects around 50 million people worldwide and is associated with lower quality of life scores, an increased risk of premature death, and significant socio-economic implications. The lack of updated evidence on current epidemiology and patient characterization creates considerable uncertainty regarding the epilepsy burden in Portugal. The study aims to characterize and quantify the epilepsy patients who have been hospitalized, with medical or surgical procedures involved, and to analyze their associated comorbidities and mortality rates. METHODS: A multicenter retrospective study was conducted using hospital production data of epilepsy patients. The study included all patients diagnosed with epilepsy-related International Classification of Diseases-9/10 codes between 2015 and 2018 in 57 Portuguese National Health Service (NHS) hospitals (n = 57 institutions). Patient characterization and quantification were done for all patients with an epilepsy diagnosis, with specific analyses focusing on those whose primary diagnosis was epilepsy. Baseline, demographic, and clinical characteristics were analyzed using descriptive statistics. RESULTS: Between 2015 and 2018, a total of 80,494 hospital episodes (i.e., patient visit that generates hospitalization and procedures) were recorded, with 18 % to 19 % directly related to epilepsy. Among these epilepsy-related hospital episodes, 13.0 % led to short term hospitalizations (less than 24 h). Additionally, the average length of stay for all these epilepsy-related episodes was 8 days. A total of 49,481 patients were identified with epilepsy based on ICD-9/10 codes. The median age of patients was 64 years (min: 0; max: 104), with a distribution of 4.8 patients per 1,000 inhabitants. From the total of deaths (9,606) between 2015 and 2018, 14% were associated with patients whose primary diagnosis was epilepsy, with 545 of these being epilepsy-related deaths. Among patients with a primary diagnosis of epilepsy, the most common comorbidities were hypertension (24%) and psychiatric-related or similar comorbidities (15%), such as alcohol dependance, depressive and major depressive disorders, dementia and other convulsions. CONCLUSION: This study showed similar results to other European countries. However, due to methodological limitations, a prospective epidemiological study is needed to support this observation. Furthermore, the present study provides a comprehensive picture of hospitalized epilepsy patients in Portugal, their comorbidities, mortality, and hospital procedures.

Fungi: friends or foes-an outreach science initiative for the collection of airborne fungal spores by high school students.

Fungi mostly reproduce through spores that are adapted for airborne dispersal; hence, fungal spores (and fungi) are found virtually everywhere. Fungi can be "friends or foes." Our friends include fungi used in the food and biotech industries, fungi that contribute to the cycling of carbon and nutrients, and those involved in the decontamination of polluted soils and/or water, to mention just a few examples. Many species, however, are foes-they are detrimental to plants, animals, and/or humans. Annually, >1.5 million people die due to invasive fungal infections. With the aim of enhancing microbiology literacy and the understanding of microbial concepts, we set up a project for the collection of airborne spores (the principal agent through which human airways are exposed to fungi). Students from five high schools in the Oeiras municipality partnered with us as citizen scientists; they carried out sampling by collecting fungal spores on adhesive stickers. The fungal spores collected by the students were subsequently processed in the schools and our research laboratory. Results obtained by the students themselves revealed a large variety of fungal species capable of growing in a rich medium at 30°C. In the research laboratory, using selective isolation conditions, 40 thermotolerant fungi were isolated, 32 of which were taxonomically identified as aspergilla, mostly from within the Aspergillus fumigatus taxa, yet exhibiting high genetic heterogeneity. The protocols and results were presented to the students, who were made aware of the local dispersal of airborne fungal spores, including some from potentially pathogenic fungi. Through carrying out scientific activities, the students developed both the interest and the self-confidence needed to implement future environmental investigations.

NmrB (AN9181) expression is activated under oxidative stress conditions acting as a metabolic repressor of Aspergillus nidulans.

Aspergilli comprise a diversity of species that have been extensively studied due to their catabolic diversity, biotechnological and ecological value, and pathogenicity. An impressive level of structural and functional conservation has been shown for aspergilli, regardless of many (yet) cryptic genomic elements. We have hypothesized the existence of conserved genes responsive to stress in aspergilli. To test the hypothesis of such conserved stress regulators in aspergilli, a straightforward computational strategy integrating well-established bioinformatic tools was used as the starting point. Specifically, five transcriptome-based datasets on exposure to organic compounds were used, covering three distinct Aspergillus species. Among the identified up-regulated genes, only one gene showed the same response in all conditions, AN9181. This gene encodes a protein containing a phenylcoumaran benzylic ether reductase-like domain and a Nitrogen metabolite repressor regulator domain (NmrA). Deletion of this gene caused significant phenotypic alterations compared to that of the parental strain across diverse conditions. Specifically, the deletion of AN9181 raised the mutant's metabolic activity in different nitrogen sources. The acquired data supports that AN9181 acts by repressing (slowing down) A. nidulans growth when exposed to aromatic compounds in a concentration dependent manner. The same phenotype was observed for amphotericin B. Finally, AN9181 underwent differential upregulation under oxidative stress conditions. Collectively, the data suggest that AN9181, herein assigned as NmrB (Nitrogen Metabolite Repression Regulator B), builds up the genetic machinery of perception of oxidative stress by negatively regulating growth under such conditions.

Pharmacogenetic Variants Can Influence Optical Medication Use.

INTRODUCTION: Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079). DPYD gene variants are associated with the enzyme dihydropyrimidine dehydrogenase deficiency (DPD; OMIM: 274270). This autosomal recessive metabolic disorder, ultimately leads to the inability to metabolize fluoropyrimidines, which causes severe toxicity in individuals treated with these drugs. METHODS: Variants in genes responsible for the expression of enzymes that encode transporters or receptors involved in the metabolization pathways of certain drugs may condition the individuals response to certain drugs, compromising the therapeutic response and clinical prognosis. Thus the sequencing and identification of variants become relevant, not only gain knowledge on effects of these variants' on disease causality but also in terms of its side effects resulting from the coding enzymes responsible for drug metabolization. RESULTS: It was found that patients with the c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) polymorphisms, in homozygosity, in FMO3 gene did not develop polyps, thus have a protective effect in the treatment of Familial Adenomatous Polyposis (PAF). However, in the case of the DPYD gene, c.1905+1G>A (IVS14+1G>A), c.1679T>G (p.Ile560Ser), c.2846A>T (p.Asp949Val) e c.1236G>A/HapB3 variants can be lethal in cancer patients indicated for fluoropyrimidine-based chemotherapy. CONCLUSION: Knowledge on the drug mechanisms will affect the therapeutic response of patients treated with a given drug. Thus, pharmacogenetics is an essential tool in personalized medicine, since molecular studies allows the clinician to predict the probability of efficacy and toxicity of certain drugs, resulting higher efficiency in individualizing treatment and also improving the safety of the patient. From a personalized medicine perspective, the study of the characteristics of the drug and its metabolization site, the genes involved in the encoding of enzymes responsible for its metabolization will be of great interest.

Multiple sclerosis under the age of ten: the challenge of a rare diagnosis in a special population - a case series.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system which, when it begins before the age of 18, is defined as paediatric MS. Most common clinical presentations include long tract involvement, brainstem/cerebellum syndromes, optic neuritis and acute disseminated encephalomyelitis. Paediatric-onset MS typically has a more inflammatory-active course and a higher lesion burden in imaging studies, but an extensive post-relapse recovery, with a slower long-term disability progression. The first demyelinating clinical attack occurs before 10 years old in less than 1% of patients, and, in this special population, the condition has particularities in clinical presentation, differential diagnosis, diagnostic assessment, current treatment options and outcome. Clinical cases: We present the cases of four Caucasian children (2 girls) diagnosed with relapsing-remitting MS before the age of ten, with a mean age at the time of the first relapse of 7.4 ± 2.4 years. Clinical presentation included optic neuritis, myelitis, brainstem syndrome, and acute disseminated encephalomyelitis. Baseline MRI identified several lesions, frequently large and ill-defined. Two patients were included in clinical trials and two patients remain in clinical and imaging surveillance. Conclusion: Diagnosis of MS before the age of 10 years is rare, but it has significant long-term physical and cognitive consequences, as well as a substantial impact on the current and future quality of life of the child and family. Early and correct diagnosis is essential. Prospective, randomized, large cohort studies are needed to assess the efficacy and safety of disease-modifying treatments in children under the age of ten.

Neutrophil/lymphocyte and monocyte/lymphocyte indexes as potential predictors of relapse at 1 year after diagnosis of pediatric multiple sclerosis: a single-center, exploratory and proof-of-concept study.

Introduction: Early identification of patients with a more unfavorable outcome in Multiple Sclerosis (MS) is crucial to optimize individualized treatment. Neutrophil-lymphocyte index (NLI) and monocyte-lymphocyte index (MLI) have been considered as potential biomarkers for disease prognosis. Our study aims to investigate the usefulness of NLI and MLI as predictors of relapse, disability progression, and lesion accumulation on magnetic resonance imaging (MRI) 1 year after diagnosis and treatment initiation, in pediatric-onset MS. Methods: A retrospective single-center study was conducted, including patients with diagnosis of MS established in pediatric age (<18 years old), at least 1-year of follow-up, and a complete blood count (CBC) performed at diagnosis. We collected the nearest-to-diagnosis NLI and MLI, as well as clinical and imaging variables, at diagnosis and 12 months later. Our cohort was further dichotomized into two groups, based on the presence of relapses. Statistical significance was considered for p < 0.05. Results: Eighteen patients (n = 18) were included. The relapsing group had higher mean, minimum, and maximum values for both NLI (5.17 ± 5.85, range: 1.57-11.92) and MLI (0.35 ± 0.22, range: 0.19-0.59), compared to the non-relapsing group (2.19 ± 1.63, range: 1.12-7.32 for NLI, and 0.24 ± 0.09, range: 0.14-0.44 for MLI). A higher percentage of patients in the relapsing group had increased NLI (>1.89, 66.7%) and MLI (>0.21, 66.7%) values than those in the non-relapsing group (46.7%). Patients who presented new T2-hyperintense lesions on MRI after 1 year of follow-up also had higher mean, minimum, and maximum values of both biomarkers. Patients who did not achieve No Evidence of Disease Activity-3 (NEDA-3) state exhibited higher values for both ratios. However, in our sample, no statistically significant correlations were found between MLI and NLI values and the clinical and imaging variables considered. Conclusion: The ease of obtaining NLI and MLI from routine blood tests renders them useful biomarkers as a screening tool in longitudinal follow-up. Our study was based on a very small sample size, but it allowed us to verify the feasibility of the protocol used. It is intended to involve other centers in the next phase of this work, testing the possible usefulness of the indices under analysis on a larger sample.

Leigh Syndrome Due to mtDNA Pathogenic Variants

Abstract Leigh syndrome is a devastating neurodegenerative disease, typically manifesting in infancy or early childhood. Hallmarks of the disease are symmetrical lesions in the basal ganglia or brain stem on MRI, and a clinical course with rapid deterioration of cognitive and motor functions. It is genetically heterogeneous, causative mutations have been disclosed in mitochondrial DNA and nuclear genes involved in the process of energy production in the mitochondria .We investigated the whole mitochondrial DNA in three Brazilian patients with LS, based on their clinical and biochemical data, with the aim to identify the disease-causing mutations. In two of the patients, with complex I deficiency, a novel heteroplasmic variant m.4142G>T (p.R279L) in MT-ND1 and a recurrent homoplasmic mutation m.10197G>A (p.A47T) in MT-ND3 were identified. In the remaining patient, with complex IV deficiency, a de novo heteroplasmic variant in MT-CO1 m.6547T>C (p.L215P) was found. The molecular investigation in mitochondrial diseases have shifted their focus from mitochondrial DNA to nuclear DNA, however, mtDNA protein-coding genes are one of the important genetic causes of mitochondrial disorders for Leigh syndrome. This study expands the molecular and clinical spectrum associated with this disease.

A acupuntura na rede pública de saúde em Uberlândia-MG / Acupuncture in the public health network in Uberlândia-MG

Introdução: A Medicina Tradicional Chinesa (MTC) consiste num conjunto complexo de técnicas terapêuticas que buscam tratar o indivíduo como um todo, através da estimulação de mecanismos naturais para gerar equilíbrio energético do corpo e proporcionar saúde. Dentre os recursos da MTC, a acupuntura é um dos mais reconhecidos e utilizados no país. É uma técnica com baixo custo de aplicação e de recursos materiais; ausência de efeitos colaterais significativos; e alta resolutibilidade. Em 2006, sua oferta na rede pública de saúde foi normatizada pela Política Nacional de Práticas Integrativas e Complementares (PNPIC). Em Minas Gerais esta normatização foi reafirmada pela Política Estadual de Práticas Integrativas e Complementares (PEPIC), em 2009. Objetivos: Este trabalho tem como objetivo descrever a organização, funcionamento do serviço e o perfil do usuário da acupuntura na unidade de referência em saúde em Uberlândia, Minas Gerais. Método: Foi realizado um estudo de caso, cuja coleta dos dados incluiu observação do fluxo de atendimento, levantamento e análise de dados dos prontuários dos usuários e entrevistas com profissionais e gestores envolvidos com a atividade. Resultados: O serviço de acupuntura é ofertado desde 2010 por um profissional especializado. Os critérios de entrada no serviço foram embasados na eficácia da técnica, respaldada em documentos divulgados pela Organização Mundial da Saúde. Os dados apontam para boa aceitação do serviço por parte dos profissionais de saúde e usuários. Deste último, prevalecem o atendimento ao sexo feminino na faixa etária entre 40 e 59 anos, com diagnóstico de patologias crônicas. De acordo com a PNPIC e PEPIC/MG, o município cumpre parcialmente as recomendações de implantação dos serviços na rede pública de saúde, não definindo claramente a destinação orçamentária e as formas de gestão. Conclusão: Uma maior institucionalização da atividade é importante para que possa se constituir em mais uma alternativa terapêutica para os usuários. Para isso, é importante conhecer a demanda e analisar sua viabilidade, bem como construir de indicadores para monitorar seus impactos à população.

Densidade de Enterococcus sp em águas recreacionais e areias de praias do município de São Vicente-SP, Brasil e sua relação com parâmetros abióticos / Density of Enterococcus sp in recreational waters and beach sandin São Vicente-SP, Brazil and its relationship to abiotic parameters

As cidades litorâneas atraem inúmeros turistas pela sua beleza cênica e atrativos recreacionais, incrementando a fonte de renda dos municípios. Dessa forma, é evidente a necessidade de programas de monitoramento da qualidade de suas praias, a fim de assegurara saúde dos banhistas. Apesar de haver um monitoramento eficaz para as águas recreacionais marinhas, ainda não existem, no Brasil, programas que atestem a qualidade das areias das praias. Nesse sentido, o presente estudo objetivou analisar a densidade de bactérias do gênero Enterococcus nas areias e águas de duas praias do município de São Vicente-SP, Brasil correlacionando com parâmetros abióticos (temperatura, salinidade, granulometria, matéria orgânica e variação de maré). Amostras de água e areia foram coletadas durante o mês de fevereiro de 2006 nas praias do Gonzaguinha e da Ilha Porchat, e as densidades das bactérias,determinadas com base na técnica de membrana filtrante. Temperatura e salinidade foram medidas in situ com o auxílio de um termômetro e um refratômetro, enquanto que granulometria e matéria orgânica foram determinadas em laboratório, de acordo com os métodos descritos por Suguio e Dean. Houve diferenças significativas entre as densidades encontradas na água e nas areias(p=0.004), sendo aproximadamente 20 vezes superior na areia das praias do Gonzaguinha. Resultado semelhante foi obtido para as amostras das praias da Ilha Porchat, sendo as densidades encontradas nas areias cerca de três vezes superior às encontradas nas amostras de água. Em ambas as praias, salinidade e temperatura correlacionaram-se de maneira negativa com as densidades obtidas, o que sugere que há um efeito deletério desses parâmetros sobre a população bacteriana. O presente estudo demonstra que há uma grande necessidade de estabelecimento de programas de monitoramento para areias de praias, visto que atualmente a avaliação da qualidade das praias é parte importante de programas de gerenciamento costeiro integrado.

Coastal cities attract a large number of tourists for their beautiful landscape and recreational activities, increasing the municipalities’income source. Thus, a need is clear for the establishment of beach quality monitoring programs to ensure bathers health. Although there is an effective monitoring program for recreational waters in Brazil there are no programs to certify the quality of beach sands. In this sense, the aim of this work was to analyze the density of bacteria from the genus Enterococcus in both sand and water from two beaches from São Vicente, São Paulo (Brazil) and correlate these densities to abiotic parameters such as: temperature, salinity, particle size, organic matter and tides). Water and sand samples were collected during February 2006 on the beaches of Gonzaguinha e Ilha Porchat and bacterial densities were determined by membrane filter technique. Temperature and salinity were measured in situwith a thermometer and a refractometer while particle size and organic matter were determined according to methods described by Suguio and Dean. There were significant differences between densities found in water and sand (p=0.004), being approximately 20times higher in Gonzaguinha’s beach sands. Similar results were found for Ilha Porchat beach samples, being the densities found insand 3 times greater than those found in water. Both beaches showed a negative correlation between bacterial densities and salinity and temperature, suggesting a deleterious effect of these parameters on the bacterial community. On the other hand, no correlation was found between organic matter and particle size and bacterial densities. This work demonstrates that there is a great necessity for monitoring beach sand since the evaluation of beach quality is an important part of integrated coastal management programs.

Avaliação antropométrica e análise dietética de pré-escolares em centros educacionais municipais no sul de Minas Gerais / Anthropometric evaluation and food intake of preschool children at municipal educational centers, in South of Minas Gerais State, Brazil

Objetivou-se avaliar as condições socioeconômicas, o estado nutricional e o consumo alimentar de pré-escolares assistidos pelos Centros Educacionais Municipais (CEM) de Alfenas (MG). Foi realizado um estudo transversal, com 186 crianças. Avaliou-se o perfil socioeconômico, peso, estatura, idade, sexo e o consumo alimentar pelo instrumento de pesagem direta dos alimentos. Observou-se renda familiar de um a três salários mínimos, ensino fundamental incompleto, casa própria com saneamento básico, quatro a cinco habitantes por domicílio, dos quais, na maioria dois trabalhavam. A média de idade foi de 49,2 ± 12,9 meses. A baixa estatura foi o desvio nutricional mais prevalente (20,5 por cento). 72,6 por cento das crianças apresentaram ingestão energética abaixo da necessidade energética estimada (EER). Ao estratificar por faixa etária, de um a três anos, 78,4 por cento das crianças apresentaram ingestão acima da EER e de quatro a seis anos, 74,1 por cento apresentaram ingestão abaixo da EER. Todas as crianças apresentaram baixo consumo de cálcio e a maioria apresentou consumo abaixo da necessidade média estimada (EAR) para ferro. Apesar de alguns fatores biossocioeconômicos serem favoráveis, os desvios nutricionais e a ingestão inadequada de nutrientes estavam presentes, tornando-se necessária implementação de programa de controle nutricional nos CEM.

The objective of this article is to evaluate socioeconomic conditions, nutritional status and food intake of preschool children assisted at Municipal Educational Centers (CEMs) of Alfenas, Minas Gerais State, Brazil. A transverse study involving 186 children was performed. The socioeconomic profile, weight, height, age, sex and food intake by a direct weighting tool were evaluated. It was observed an income family of one to three minimum wages, incomplete fundamental learning, private house with basic sanitation, four to five inhabitants per house of whom two worked at most. The average age was 49.2 ± 12.9 months. The stunting rates were more prevalent among the children (20.5 percent). The whole, 72.6 percent of children have energy intake below Estimated Energy Intake (EER). However, when stratifying for age group, 78.4 percent of the children from 1 to 3 years old have high energy intake and 74.1 percent from 4 to 6 years old have inadequate energy intake. All children presented consumption below the Adequate Intake (AI) of calcium and most of them below to Estimated Average Requirement (EAR) of iron. Despite some biosocioeconomic factors be favorable to the nutritional status, malnutrition, and inadequate nutrient intake were present, which demanded the implementation of nutritional programs in CEMs.

Influence of method and period of storage on the microtensile bond strength of indirect composite resin restorations to dentine

This study evaluated the influence of the method and period of storage on the adhesive bond strength of indirect composite resin to bovine dentin. Ninety bovine incisors were stored in three different solutions: 0.2 percent thymol, 10 percent formalin, and 0.2 percent sodium azide, during 3 periods of storage: 7 days, 30 days and 6 months, resulting in 9 groups (n = 10). The roots were cut off and the buccal surface was ground with #600-grit silicon carbide paper. The surface was conditioned with 37 percent phosphoric acid for 15 s and a composite resin restoration (TPH Spectrum) was fixed using a one-bottle adhesive system (Adper Single Bond) and a dual-cured resinous cement (Rely X ARC) under a load of 500 g for 5 minutes. The samples were serially cut perpendicular to the bonded interface to obtain slices of 1.2 mm in thickness. Each slab was trimmed with a cylindrical diamond bur resulting in an hourglass shape with a cross-sectional area of approximately 1 mm². The microtensile bond strength (μTBS) testing was performed in a testing machine (EMIC 2000 DL) at a 0.5 mm/minute crosshead-speed until failure. After fracture, the specimens were examined under SEM to analyze the mode of fracture. μTBS Means were expressed in MPa and the data were analyzed by two-way ANOVA (3X3) and the Tukey test (α = 0.05). The storage times of 7 and 30 days produced no significant difference irrespective of the solution type. The formalin and thymol solutions, however, did have a negative influence on bond strength when the teeth were stored for 6 months.

Evolução do teor de arginina e de uréia na fermentação alcoólica do mosto da cv Gewürztraminer com diferentes níveis de adubação nitrogenada / Arginine and urea evolution during musts fermentation of cv Gewürztraminer from different nitrogen fertilizer levels in the soil

O experimento foi realizado com a cv. Gewürztraminer proveniente de Santana do Livramento. As videiras desta cultivar foram submetidas a diferentes tratamentos nitrogenados realizados durante o período vegetativo de 1992 a 1993. Após a colheita e esmagamento da uva, o mosto obtido foi dividido em quatro lotes e microvinificado com diferentes leveduras. Durante a fermentação ocorreu uma diminuição na concentração de arginina e um aumento na concentração de uréia, porém da metade para o fim da fermentação as leveduras reabsorveram parte da uréia excretada.

The experiment was done with the grape variety Gewürztraminer from Santana do Livramento, RS. The vineyard was treated with different nitrogen treatments during the 1992-1993 season. After harvest and crush, the must from each treatment was divided into four lots, and in each one was added a different yeast. During fermentation arginine decreased and urea increased. However, near the end of the fermentation process the available N urea started to be absorbed by the yeast.