Checklist of Omophoita Chevrolat, 1836 (Coleoptera: Chrysomelidae: Galerucinae: Alticini) and diagnoses for some species from southern Brazil: notes on the taxonomic history, redescriptions and new records.

Morphological descriptions, taxonomic history and distribution data of Omophoita species recorded for southern Brazil (states of Paran, Santa Catarina and Rio Grande do Sul) are presented. Through the analysis of the existing literature, databases, loaned material, and specimen collecting, we studied seven species of Omophoita recorded for southern Brazil: O. communis (Bechyn 1959), O. equestris (Fabricius 1787), O. magniguttis (Bechyn 1955), O. octoguttata (Fabricius 1775), O. personata (Illiger 1807), O. sesquilunata (Klug 1829), and O. sexnotata (Harold 1876). We report O. sesquilunata for this region for the first time. Updated morphological descriptions, including novel information for male and female genitalia are presented for those taxa with dissected specimens.

Concentration, Propagation and Dilution of Toxic Gases in Underground Excavations under Different Ventilation Modes.

The drill-and-blast method is widely used for the excavation of hard rock tunnels. Toxic gases such as carbon monoxide and nitrogen oxides are released immediately after blasting by the detonation of explosives. To provide a safe working environment, the concentration of noxious gases must be reduced below the threshold limit value according to health and safety regulations. In this paper, one-dimensional mathematical models and three-dimensional CFD numerical simulations were conducted to analyze the concentration, propagation and dilution of the blasting fumes under different operating conditions. Forced, exhaust and mixed ventilation modes were compared to determine the safe re-entry times after blasting in a 200 m-long tunnel excavated using the top-heading-and-benching method. Based on the numerical simulations, carbon monoxide was the most critical gas, as it required a longer ventilation time to reduce its concentration below the threshold limit value. The safe re-entry time reached 480 s under the typical forced ventilation mode, but was reduced to 155 s when a mixed ventilation system was used after blasting, reducing the operating costs. The reduction of the re-entry time represents a significant improvement in the excavation cycle. In addition, the results obtained show that 1D models can be used to preliminary analyze the migration of toxic gases. However, to reliably determine the safe re-entry times, 3D numerical models should be developed. Finally, to verify the accuracy of the CFD results, field measurements were carried out in a railway tunnel using gas sensors. In general, good agreements were obtained between the 3D numerical simulations and the measured values.

Treatment of Soil Contaminated by Mining Activities to Prevent Contamination by Encapsulation in Ceramic Construction Materials.

Mining is an essential activity for obtaining materials necessary for the well-being and development of society. However, this activity produces important environmental impacts that must be controlled. More specifically, there are different soils near new or abandoned mining productions that have been contaminated with potentially toxic elements, and currently represent an important environmental problem. In this research, a contaminated soil from the mining district of Linares was studied for its use as a raw material for the conforming of ceramic materials, bricks, dedicated to construction. Firstly, the contaminated soil was chemically and physically characterized in order to evaluate its suitability. Subsequently, different families of samples were conformed with different percentages of clay and contaminated soil. Finally, the conformed ceramics were physically and mechanically characterized to examine the variation produced in the ceramic material by the incorporation of the contaminated soil. In addition, in this research, leachate tests were performed according to the TCLP method determining whether encapsulation of potentially toxic elements in the soil occurs. The results showed that all families of ceramic materials have acceptable physical properties, with a soil percentage of less than 80% being acceptable to obtain adequate mechanical properties and a maximum of 70% of contaminated soil to obtain acceptable leachate according to EPA regulations. Therefore, the maximum percentage of contaminated soil that can be incorporated into the ceramic material is 70% in order to comply with all standards. Consequently, this research not only avoids the contamination that contaminated soil can produce, but also valorizes this element as a raw material for new materials, avoiding the extraction of clay and reducing the environmental impact.

Material Behavior and Fatigue Assessment of Old Steel Bridges of the Spanish Conventional Rail Network.

This work presented salient features of the steel behavior of seven metallic bridges close to, or over, 100 years old, among the Spanish conventional rail network as well as the results of a fatigue life expectancy study. A preliminary study of the properties of the constituent materials obtained from the bridges samples was carried out followed by dynamic fatigue tests under service representative loads. Due to the steelmaking techniques in the late 19th and early 20th centuries, disperse fatigue behavior results were obtained. However, the wide safety margins with which these bridges were designed, as well as the mechanical properties of the steel (relatively good mechanical resistance but with low ductility), seem to guarantee a long fatigue life. This estimate decreases sharply with increasing loads.

Embolismo pulmonar masivo y trombo en ventrículo derecho postinfarto agudo de miocardio / Massive pulmonary embolism and right ventricle thrombus post-acute myocardial infarct

Resumen Introducción: un trombo en ventrículo derecho y embolismo pulmonar post infarto agudo de miocardio sin elevación del ST es muy inusual. Es considerado una emergencia médica y es imperativo instaurar una opción terapéutica inmediata. Presentación del caso: paciente femenina de 80 años quien consultó en sala de emergencias por síncope, dolor torácico y disnea persistente. Se confirmó síndrome coronario agudo por electrocardiograma y troponina I elevada. En estudios complementarios se encontró hallazgo incidental de trombo en el ventrículo derecho y un angio-TAC confirmó embolismo pulmonar masivo. Discusión: el trombo en ventrículo derecho y embolismo pulmonar masivo post infarto es un fenómeno muy raro en el escenario clínico, debido a la instauración temprana de la terapia anti-isquémica. Es necesario mayor investigación para aclarar este fenómeno.

Abstract Introduction: right ventricular thrombus and pulmonary embolism after acute myocardial infarction without ST elevation is very unusual. It is considered a medical emergency and it is imperative to establish an immediate therapeutic option. Case presentation: An 80-year-old female patient visited the emergency room for syncope, chest pain, and persistent dyspnea. Acute coronary syndrome was confirmed by electrocardiogram and elevated troponin I. In complementary studies, an incidental finding of a thrombus in the right ventricle was found and a CT angiography confirmed massive pulmonary embolism. Discussion: thrombus in the right ventricle and massive post-infarction pulmonary embolism is a very rare phenomenon in the clinical setting due to the early introduction of anti-ischemic therapy. More research is needed to clarify this phenomenon.

Características sociodemográficas e histopatológicas en pacientes con cáncer gástrico en una población con alto riesgo en Colombia / Sociodemographic and histopathological characteristics of patients with gastric cancer in a high-risk population in Colombia

Resumen Objetivo: describir las características sociodemográficas e histopatológicas en pacientes con diagnóstico de adenocarcinoma gástrico en la Clínica Oncológica Aurora, durante el período 2014-2017 en la ciudad de Pasto, Colombia. Métodos: se realizó un estudio descriptivo en una cohorte de 54 pacientes con diagnóstico de cáncer gástrico sometidos a gastrectomía durante los años 2014 a 2017. La información sociodemográfica se obtuvo a través de la historia clínica. El sistema de Sydney y la clasificación de Lauren se usaron para determinar las características histopatológicas. Resultados: la mayoría de los tumores se presentó en hombres mayores de 50 años (relación hombre mujer de 2,6:1). La ubicación predominante fue la región antropilórica. El histotipo tumoral más frecuente fue el intestinal (80%). La prevalencia de Helicobacter pylori en pacientes fue del 24,07% y fue mayor en el histotipo intestinal. La metaplasia intestinal fue la lesión premaligna más prevalente en todos los histotipos tumorales. Conclusiones: en el presente estudio se encontró que la edad mayor a 50 años y el sexo masculino son condiciones asociadas con el cáncer gástrico; hallazgo ya demostrado en estudios previos. Es perentorio avanzar en el mejoramiento de las condiciones de salud pública, control de la infección por H. pylori y tamizaje temprano de lesiones premalignas, pues son factores determinantes en la carcinogénesis de pacientes con carcinomas no cardiales e histotipos intestinales ubicados en la región antrocorporal. Aunque no se encontraron diferencias significativas entre los histotipos tumorales, el adenocarcinoma de tipo intestinal ubicado en la región antropilórica fue el diagnóstico más frecuente.

Abstract Objective: To describe the sociodemographic and histopathological characteristics of patients diagnosed with gastric adenocarcinoma at the Clínica Oncológica Aurora between 2014 and 2017 in the city of Pasto, Colombia. Methodology: A descriptive study was carried out in a cohort of 54 patients diagnosed with gastric cancer who underwent gastrectomy between 2014 and 2017. Sociodemographic information was taken from the medical records of the patients. The Sydney system and Lauren classification were used to determine histopathological characteristics. Results: Most tumors were found in men older than 50 years (with a male:female ratio of 2.6:1). The predominant location was the antropyloric region. The most frequent tumor histotype was intestinal (80%). The prevalence of Helicobacter pylori in patients was 24.07 % and it was most commonly found in the intestinal histotype. Intestinal metaplasia was the most prevalent premalignant lesion in all tumor histotypes. Conclusions: The present study found that the age of 50 and the male sex are conditions associated with gastric cancer. This finding has already been demonstrated in previous studies. Progress in improving public health conditions, controlling H. pylori infection, and early screening of premalignant lesions is imperative, as they are determining factors of carcinogenesis in patients with non-cardia carcinomas and intestinal histotypes located in the anthrocorporal region. Although no significant differences were found among tumor histotypes, intestinal adenocarcinoma in the antropyloric region was the most frequent diagnosis.

Papez Circuit Gray Matter and Episodic Memory in Amyotrophic Lateral Sclerosis and Behavioural Variant Frontotemporal Dementia.

Amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia are two different diseases recognized to overlap at clinical, pathological and genetic characteristics. Both conditions are traditionally known for relative sparing of episodic memory. However, recent studies have disputed that with the report of patients presenting with marked episodic memory impairment. Besides that, structural and functional changes in temporal lobe regions responsible for episodic memory processing are often detected in neuroimaging studies of both conditions. In this study, we investigated the gray matter features associated with the Papez circuit in amyotrophic lateral sclerosis, behavioural variant frontotemporal dementia and healthy controls to further explore similarities and differences between the two conditions. Our non-demented amyotrophic lateral sclerosis patients showed no episodic memory deficits measured by a short-term delayed recall test while no changes in gray matter of the Papez circuit were found. Compared with the amyotrophic lateral sclerosis group, the behavioural variant frontotemporal dementia group had lower performance on the short-term delayed recall test and marked atrophy in gray matter of the Papez circuit. Bilateral atrophy of entorhinal cortex and mammillary bodies distinguished behavioural variant frontotemporal dementia from amyotrophic lateral sclerosis patients as well as atrophy in left cingulate, left hippocampus and right parahippocampal gyrus. Taken together, our results suggest that sub-regions of the Papez circuit could be differently affected in amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia.

Necrotising enterocolitis in newborns receiving diazoxide.

BACKGROUND: Frequent and severe gastrointestinal disturbances have been reported with the use of diazoxide in adults and older children. However, no studies have investigated the incidence of necrotising enterocolitis (NEC) in diazoxide-exposed newborns. OBJECTIVE: To evaluate a possible association between diazoxide treatment for neonatal hypoglycaemia and the occurrence of NEC. DESIGN: Multicentre retrospective cohort study. SETTING: Three tertiary neonatal intensive care units in Toronto, Canada. PATIENTS: All patients treated with diazoxide for persistent hypoglycaemia between July 2012 and June 2017 were included. Overall incidence of NEC during those years on the participating units was obtained for comparison from the Canadian Neonatal Network database. MAIN OUTCOME: Incidence of NEC after diazoxide exposure. RESULTS: Fifty-five neonates were exposed to diazoxide during the study period. Eighteen patients (33%) showed signs of feeding intolerance, and 7 developed NEC (13%). A diagnosis of NEC was more prevalent in the diazoxide-exposed, as compared with non-exposed infants of similar gestational age (OR 5.07, 95% CI 2.27 to 11.27; p<0.001), and greatest among infants born at 33-36 weeks' gestation (OR 13.76, 95% CI 3.77 to 50.23; p<0.001). All but one of the neonates diagnosed with NEC developed the disease within 7 days from initiation of diazoxide treatment. CONCLUSION: The present data suggest a possible association between diazoxide exposure and the development of NEC in neonates. Further evaluation of the diazoxide-associated risk of NEC in neonates treated for persistent hypoglycaemia is warranted.

CAG repeats ≥ 34 in Ataxin-1 gene are associated with amyotrophic lateral sclerosis in a Brazilian cohort.

Little is known about the genetic basis of amyotrophic lateral sclerosis (ALS) outside Europe and US. In this study, we investigated whether intermediate CAG expansions at ATXN1 were associated to ALS in the Brazilian population. To accomplish that, representative samples from 411 unrelated patients and 436 neurologically normal controls from 6 centers spread over the territory were genotyped to quantify ATXN1 expansions. We found that ATXN1 intermediate-length expansion (≥34 CAG repeats) are associated with the disease (odds ratio = 2.19, 95% CI = 1.081-4.441, p = .026). Most ATXN1-positive patients had classical phenotype, but some of them presented predominant lower motor neuron involvement. None of them had associated ataxia. Frontotemporal dementia was concomitantly found in 12.5% of patients carrying the intermediate ATXN1 expansion. Further studies are needed to validate these findings and to understand the pathophysiological mechanisms that connect ataxin-1 and ALS.

A multifaceted small RNA modulates gene expression upon glucose limitation in Staphylococcus aureus.

Pathogenic bacteria must rapidly adapt to ever-changing environmental signals resulting in metabolism remodeling. The carbon catabolite repression, mediated by the catabolite control protein A (CcpA), is used to express genes involved in utilization and metabolism of the preferred carbon source. Here, we have identified RsaI as a CcpA-repressed small non-coding RNA that is inhibited by high glucose concentrations. When glucose is consumed, RsaI represses translation initiation of mRNAs encoding a permease of glucose uptake and the FN3K enzyme that protects proteins against damage caused by high glucose concentrations. RsaI also binds to the 3' untranslated region of icaR mRNA encoding the transcriptional repressor of exopolysaccharide production and to sRNAs induced by the uptake of glucose-6 phosphate or nitric oxide. Furthermore, RsaI expression is accompanied by a decreased transcription of genes involved in carbon catabolism pathway and an activation of genes involved in energy production, fermentation, and nitric oxide detoxification. This multifaceted RNA can be considered as a metabolic signature when glucose becomes scarce and growth is arrested.

Deficits in Emotion Recognition as Markers of Frontal Behavioral Dysfunction in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with prominent motor symptoms. Patients with ALS may also manifest frontal behavior symptoms and cognitive decline, including impairment in facial emotion recognition. The authors aimed to investigate whether deficits in emotion recognition were associated with frontal behavior symptoms in ALS. METHODS: Participants were patients with probable or definite sporadic ALS (N=21; male:female ratio, 11:10; median age, 62 years; median disease duration, 3 years) and age-matched and education-matched healthy control subjects (N=25; male:female ratio, 14:11; median age, 61 years). The Facial Emotion Recognition Test (FERT) was administered to all participants. Patients with ALS were assessed using the Cambridge Behavior Inventory-Revised and were classified into two groups according to the presence of frontal behavioral symptoms: ALS with no behavioral symptom (ALSns; N=9) and ALS with at least one behavioral symptom (ALSbs; N=12). RESULTS: Apathy and mood symptoms were the most frequent neuropsychiatric symptoms in the patient group. Patients with ALS performed worse than control subjects in the recognition of sadness (p<0.004). There were no differences between control subjects and patients in the ALSns group in all FERT scores, but the ALSbs group had lower performance than control subjects in sadness (p<0.003). CONCLUSIONS: Emotion recognition deficit may be a marker of frontal behavior in ALS.

Longitudinal assessment of clinical and inflammatory markers in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate potential associations between clinical features and inflammatory markers in patients with amyotrophic lateral sclerosis (ALS). METHODS: A consecutive series of 68 patients (39 males and 29 females) with sporadic ALS were subjected to a comprehensive clinical assessment and blood draw. A subset of these patients underwent a new assessment within 6-12 months after the baseline visit. In addition, a group of 62 subjects composed by age and sex-matched healthy subjects (38 males and 24 females) was enrolled in this study. Peripheral blood was drawn and plasma levels of chemokines and cytokines were measured by cytometric bead array and enzyme-linked immunosorbent assay. RESULTS: Our sample was composed by patients with ALS with an average age of 58 (±12.3) years old and 3 (±2.7) years of disease length at the baseline visit. Patients with ALS presented increased plasma levels of interleukin (IL)-6 and IL-8 in comparison with controls. After multivariate analysis, higher levels of IL-6 and lower levels of IL-2 were significantly associated with increased likelihood of ALS diagnosis. When evaluating the subset of patients assessed longitudinally, we did not find any significant difference in the levels of inflammatory markers between the two time points. Older age at ALS onset was the only factor associated with a faster rate of disease progression. CONCLUSIONS: IL-6 levels could discriminate between ALS and controls and may be regarded as a potential biomarker of ALS diagnosis. An increase in IL-2 levels was associated with a protective effect on the odds of ALS diagnosis. Older age at ALS onset predicted a fast rate of disease progression.

Factores de riesgo de mala evolución en la reparación de hernias incisionales: Lecciones aprendidas del Registro Nacional de Hernia Incisional (EVEREG) / Risk factors for bad outcomes in incisional hernia repair: Lessons learned from the National Registry of Incisional Hernia (EVEREG)

INTRODUCCIÓN: Los registros son herramientas potentes para identificar situaciones de riesgo de mala evolución. Nuestro objetivo ha sido analizar los datos del Registro Nacional de Hernia Incisional (EVEREG) para detectar situaciones de riesgo para el desarrollo de complicaciones y recidivas. MÉTODOS: Se analizan los datos de la cohorte de hernias registradas en el período desde julio de 2012 hasta junio de 2014. Se realiza una comparación estadística entre las hernias que presentaron complicaciones y recidivas, y su relación con los pacientes, las características de las hernias y la técnica quirúrgica, para determinar cuáles de ellos pueden predecir malos resultados. RESULTADOS: En el período de estudio disponemos de datos de 1.336 hernias (43,7% varones; 56,3% mujeres), con una edad media de 63,6 años (DE: 12,4) e IMC de 30,4 (DE: 5,4). En el estudio multivariante las variables asociadas a la presencia de complicaciones fueron: edad superior a 70 años, neoplasia, longitud del defecto mayor de 10 cm, reparación previa y resección intestinal. Las variables asociadas a recidiva fueron: las hernias paraestomales, la reparación previa, la cirugía urgente, la aparición de complicaciones postoperatorias y la reintervención quirúrgica. El uso de una separación de componentes fue el único factor protector en este tipo de análisis (OR: 0,438; IC: 0,27-0,71; p = 0,001). CONCLUSIONES: La presencia de factores de riesgo para la aparición de complicaciones y recurrencias debe ser tenida en cuenta con el fin de proyectar la prehabilitación del paciente para la cirugía, planificar la técnica quirúrgica y su derivación a unidades especializadas

INTRODUCTION: Registries are powerful tools for identifying factors predicting bad results. Our objective was to analyse data from the Spanish Registry of Incisional Hernia (EVEREG) to detect risk situations for the development of complications and recurrences. METHODS: We have analysed data of the cohort of hernias registered during the period from July 2012 to June 2014. We have compared the data between complicated and non-complicated patients in the short and long term follow-up. Data compared were: patient demographics, comorbid condition, hernia defect characteristics and surgical technique to determine which of them may be predictors of poor outcomes. RESULTS: During the period of study, we collected data from 1,336 hernias (43.7% males; 56.3% females) with a mean age of 63.6 years (SD 12.4) and BMI of 30.4 (SD 5.4). In the multivariate analysis, factors associated with complications were: age >70 years, previous neoplasm, diameter greater than 10cm, previous repair and bowel resection. Factors related with recurrences were: parastomal hernia, previous repair, emergency repair, postoperative complications and reoperation. A separation of components was the only protective factor for this type of analysis (OR 0.438; CI 0.27-0.71; p = 0.0001). CONCLUSIONS: Risk factors for the development of complications and recurrences must be considered for promoting preoperative patient prehabilitation, planning the surgical technique and referring patients to specialized abdominal wall units

Neuroinflamação na esclerose lateral amiotrófica / Neuroinflammation in amyotrophic lateral sclerosis

A esclerose lateral amiotrófica (ELA) esporádica é uma doença neurodegenerativa que acomete o neurônio motor. Sua etiologia ainda não foi totalmente esclarecida e é considerada multifatorial. O objetivo desse trabalho é fazer uma revisão narrativa sobre os mecanismos fisiopatológicos da ELA esporádica, com foco no papel da neuroinflamação, além de descrever estudos envolvendo a pesquisa de biomarcadores de diagnóstico e prognóstico. O processo de neuroinflamação na ELA é considerado secundário às alterações que levam à morte neuronal, podendo influenciar na taxa de progressão da doença. Existem diversos estudos sobre o perfil dos fatores inflamatórios na ELA, por vezes com resultados contraditórios, reforçando a dificuldade de análise desses fatores num organismo dinâmico. Ainda assim, no contexto da ELA, o estudo de possíveis biomarcadores diagnósticos e/ou prognósticos é válido e de grande interesse, pois permitiria um avanço nos ensaios clínicos que buscam novos tratamentos, bem como na condução e planejamento de cada caso.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the motor neuron. Its etiology has not been fully clarified and is considered multifactorial. The aim of this sudy is to perform a narrative review on the pathophysiological mechanisms of sporadic ALS, focusing on the role of neuroinflammation. It will also discuss studies investigating diagnostic and prognostic biomarkers. Neuroinflammation in ALS is considered to be a secondary event, triggered by neuronal death, and it may influence disease progression. There are several studies on inflammatory factors in ALS, some with contradictory findings, reinforcing the difficulty of assessing these factors in a dynamic organism. Even so, in ALS context, the study of possible diagnostic and/or prognostic biomarkers is valid and of great interest. This may allow the advance of clinical trials that investigate new treatments, as well as the management of individual cases.

Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients.

Intermediate-length cytosine-adenine-guanine nucleotide repeat expansions in the ATXN2 gene (which encodes for the protein Ataxin-2) have been linked to increased risk for amyotrophic lateral sclerosis (ALS) in different populations. There is no such study in the Brazilian population, which has a mixed ethnic background. We have thus selected 459 patients with ALS (372 Sporadic ALS and 87 Familial ALS) and 468 control subjects from 6 Brazilian centers to investigate this point. We performed polymerase chain reaction to determine the length of the ATXN2 alleles. Polymerase chain reaction products were resolved using capillary electrophoresis on ABI 3500 × l capillary sequencer. We found that ATXN2 intermediate-length expansions (larger than 26 repeats) were associated with an increased risk for ALS (odds ratio = 2.56, 95% confidence interval: 1.29-5.08, p = 0.005). Phenotype in patients with and without ATXN2 expansions was similar. Our findings support the hypothesis that ATXN2 plays an important role in the pathogenesis of ALS also in the Brazilian population.

Risk factors for bad outcomes in incisional hernia repair: Lessons learned from the National Registry of Incisional Hernia (EVEREG). / Factores de riesgo de mala evolución en la reparación de hernias incisionales: Lecciones aprendidas del Registro Nacional de Hernia Incisional (EVEREG).

INTRODUCTION: Registries are powerful tools for identifying factors predicting bad results. Our objective was to analyse data from the Spanish Registry of Incisional Hernia (EVEREG) to detect risk situations for the development of complications and recurrences. METHODS: We have analysed data of the cohort of hernias registered during the period from July 2012 to June 2014. We have compared the data between complicated and non-complicated patients in the short and long term follow-up. Data compared were: patient demographics, comorbid condition, hernia defect characteristics and surgical technique to determine which of them may be predictors of poor outcomes. RESULTS: During the period of study, we collected data from 1,336 hernias (43.7% males; 56.3% females) with a mean age of 63.6 years (SD 12.4) and BMI of 30.4 (SD 5.4). In the multivariate analysis, factors associated with complications were: age >70 years, previous neoplasm, diameter greater than 10cm, previous repair and bowel resection. Factors related with recurrences were: parastomal hernia, previous repair, emergency repair, postoperative complications and reoperation. A separation of components was the only protective factor for this type of analysis (OR 0.438; CI 0.27-0.71; p=0.0001). CONCLUSIONS: Risk factors for the development of complications and recurrences must be considered for promoting preoperative patient prehabilitation, planning the surgical technique and referring patients to specialized abdominal wall units.

The frequency of the C9orf72 expansion in a Brazilian population.

G4C2 hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). In this study, we investigated the presence of the G4C2 repeat expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and 67 FTD, and in 63 healthy controls in the southeastern region of Brazil. The highest frequencies of the C9orf72 mutation were in the ALS-FTD group (50% of familial and 17.6% of sporadic cases), although it was also present in 5% of pure ALS/motor neuron disease patients (11.8% of familial and 3.6% of sporadic cases) and in 7.1% of pure familial FTD. Among G4C2 repeat mutation carriers, 68.8% of the subjects who developed dementia symptoms were females. This frequency was significantly higher than the percentage reached by men with C9orf72 expansion who had this phenotype (p = 0.047). No abnormal repeat expansion was found in control groups. Inclusion of the C9orf72 genetic test in the molecular panels for Brazilian populations with these neurodegenerative diseases should be strongly considered.

Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway.

AIM: To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular mTOR pathway in the stomach. METHODS: Sprague Dawley rats were treated with vehicle, rimonabant, rapamycin or rapamycin+rimonabant. Gastric tissue obtained from the animals was used for biochemical assays: Nucb2 mRNA measurement by real time PCR, gastric Nucb2/nesfatin protein content by western blot, and gastric explants to obtain gastric secretomes. Nucb2/nesfatin levels were measured in gastric secretomes and plasma using enzyme-linked immunosorbent assay. RESULTS: The inhibition of cannabinoid receptor 1 (CB1) by the peripheral injection of an inverse agonist, namely rimonabant, decreases food intake and increases the gastric secretion and circulating levels of Nucb2/nesfatin-1. In addition, rimonabant treatment activates mTOR pathway in the stomach as showed by the increase in pmTOR/mTOR expression in gastric tissue obtained from rimonabant treated animals. These effects were confirmed by the use of a CB1 antagonist, AM281. When the intracellular pathway mTOR/S6k was inactivated by chronic treatment with rapamycin, rimonabant treatment was no longer able to stimulate the gastric secretion of Nucb2/nesfatin-1. CONCLUSION: The peripheral cannabinoid system regulates food intake through a mechanism that implies gastric production and release of Nucb2/Nesfatin-1, which is mediated by the mTOR/S6k pathway.