Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB.

The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients.

Parameterization of a coarse-grained model of cholesterol with point-dipole electrostatics.

We present a new coarse-grained (CG) model of cholesterol (CHOL) for the electrostatic-based ELBA force field. A distinguishing feature of our CHOL model is that the electrostatics is modeled by an explicit point dipole which interacts through an ideal vacuum permittivity. The CHOL model parameters were optimized in a systematic fashion, reproducing the electrostatic and nonpolar partitioning free energies of CHOL in lipid/water mixtures predicted by full-detailed atomistic molecular dynamics simulations. The CHOL model has been validated by comparison to structural, dynamic and thermodynamic properties with experimental and atomistic simulation reference data. The simulation of binary DPPC/cholesterol mixtures covering the relevant biological content of CHOL in mammalian membranes is shown to correctly predict the main lipid behavior as observed experimentally.

Distribution of non-native suckermouth armoured catfish Pterygoplichthys ambrosettii in the upper Paraná River basin, Brazil.

This study describes the invasion of the upper Paraná River basin by Pterygoplichthys ambrosettii based on a literature review and field samples. Pterygoplichthys ambrosettii has been reported in 42 localities throughout the upper Paraná River basin, including the Tietê, Paranapanema, Paraná, Grande and Aguapeí rivers. The ascent of P. ambrosettii after the inundation of the Sete Quedas Falls on the Paraná River and the release of individuals by aquarium hobbyists were the primary drivers of this invasion.

First record of non-native hybrid catfish Pseudoplatystoma reticulatum × Leiarius marmoratus in the Upper Paraná River basin, Brazil.

The aim of this study is to report the presence of a three non-native hybrid long-whiskered catfishes (family Pimelodidae) in the Upper Paraná River basin, Brazil. Genetic analyses demonstrated that the three presumptive hybrids were a result of the crossbreeding of Pseudoplatystoma reticulatum (central Amazonas River basin and Lower Paraná River) and Leiarius marmoratus (Amazonas, Essequibo and Orinoco rivers), producing a hybrid commonly known in Brazil as cachandiá. The potential threat to biodiversity, due to possible genetic contamination, competition and predation of wild stocks, of such artificially produced hybrid fishes is discussed.

Long-term changes in the fish assemblage of a neotropical hydroelectric reservoir.

The changes in the fish assemblage of the Capivara Reservoir, Brazil, were assessed over a 20 year period. Of 50 native fishes present in the initial samples, 27 were no longer present in the final samples, but there had been an addition of 11 invasive fishes, suggesting the occurrence of substantial shifts in fish diversity and abundance.

Cultural adaptation and validation of the Spanish version of the Cow's Milk-related Symptom Score (CoMiSS) for cow's milk protein allergy.

INTRODUCTION AND AIMS: The prevalence of cow's milk protein allergy in the first year of life varies from 1.8 to 7.5%. The Cow's Milk-related Symptom Score (CoMiSS) was published in 2014 and facilitates the diagnosis of cow's milk protein allergy. It is not meant to replace the clinical diagnosis, but rather to guide the treating team in the diagnostic process and reduce unnecessary diets. The aim was to translate the CoMiSS from English to Spanish and culturally adapt and validate the resulting Spanish version. MATERIALS AND METHODS: An adaptation and validation study on the CoMiSS questionnaire was carried out in two phases: First, the CoMiSS was translated from English to Spanish, after which interrater reliability of the translated score was assessed. Second, interrater reliability tests were carried out on 32 pediatric patients under 7 years of age that were treated for the first time at the Food Allergy Clinic of the Hospital Italiano de Buenos Aires, were suspected of having cow's milk protein allergy, and had not received any treatment, within the time frame of May 2018 and May 2019. RESULTS: Thirty-two patients were evaluated, 14 of whom were females (45%), and the median patient age was 3 months (IQR 2-4). The median result of the first measurement of the scale was 7.0 (IQR 4.5-9.0) and the median of the second measurement was 5.0 (IQR 4.0-8.0). The final intraclass correlation coefficient was 0.80 (95% CI 0.63-0.9). CONCLUSION: The Spanish translation of the CoMiSS was comparable to the original English version, with excellent interrater reliability. This simple and little-known tool has the benefit of being a noninvasive, rapid, reliable, and easy-to-use strategy.

Epidemiologic trend of pediatric inflammatory bowel disease in Latin America: The Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) Working Group.

INTRODUCTION AND AIMS: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. MATERIALS AND METHODS: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005-2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. RESULTS: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn's disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. CONCLUSIONS: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.

Prevalence of newcastle disease virus in broiler chickens (Gallus gallus) in Brazil.

This study was carried out during 2002/2003, aiming to determine the prevalence of virulent Newcastle disease virus strains (NDV) in Brazilian commercial poultry farms. Clinical samples were obtained from the Southeastern, Southern and Central-Western regions, which comprise the main area of the Brazilian poultry production. Serum samples and tracheal and cloacal swabs of 23,745 broiler chickens from 1,583 flocks, including both vaccinated chickens and those with no vaccination information, were tested for NDV using a diagnostic ELISA kit. The seropositivity was 39.1%, and the isolation percentage by flock varied from 1.0 to 7.6%, and by region from 6.5 to 58.4%. Higher isolation rates (74.3-83.3%) were obtained after three passages in embryonated chicken eggs. All isolates preliminarily identified as NDV were characterized as nonpathogenic strains, as their Intracerebral Pathogenicity Index (ICPI) was below 0.7. Based on results of this study, Brazil can claim a virulent NDV-free status for commercial flocks.

A survey for maintenance of virulent newcastle disease virus-free area in poultry production in Brazil.

In 2003, Brazil was recognized as a pathogenic Newcastle Disease Virus (NDV) strain-free country for commercial poultry. This research was conducted in Brazil between December 2003 and March 2005 to verify the maintenance of this virulent NDV-free status. Serum samples from 5,455 flocks for commercial poultry farms were collected, comprising 81,825 broiler chickens. The farms were located in nine states of the country, grouped in three geographic regions. Serological evidence of NDV infection was detected in 28.8% of the surveyed farms. However, all fifteen viruses isolated and identified as Newcastle Disease Virus (NDV) were characterized as nonpathogenic strains, based on the Intracerebral Pathogenicity Index. These results showed that Brazil preserves the virulent NDV-free status for commercial flocks.

False negative chest X-Rays in patients affected by COVID-19 pneumonia and corresponding chest CT findings.

Due to the wide availability, rapid execution, low cost, and possibility of being acquired at the patient's bed, chest X-Ray is a fundamental tool in the diagnosis, follow-up and evaluation of the treatment effectiveness of patients with pneumonia, also in the context of COVID-19 infection. However, false negative cases are possible. We report 4 cases of false negative chest X-Rays, in patients who were diagnosed positive for COVID-19 by real-time transverse-transcript-polymerase chain reaction (RT-PCR), and executed chest unenhanced CTs just after the X-Rays, demonstrating signs of COVID-19 pneumonia.

Example of antimicrobial stewardship program in a community hospital in Italy.

BACKGROUND: Inappropriate use of antibiotics has caused the emergence of resistant strains of bacteria. The hospital of Alessandria, Italy, implemented an antimicrobial stewardship (AS) pilot program between 2013 and 2015 in the intensive care units (ICUs) and internal medicine departments of Casale Monferrato and Tortona. We aimed to describe the project, results at the end of the intervention, and its strengths and weaknesses. METHODS: The protocol, designed by the local infection control committee, included three consecutive steps: local guidelines for empirical antibiotic therapy and list of prescription antibiotics with justification, monitoring of antibiotic consumption and antimicrobial resistance trend, and peer-to-peer audit sessions in the wards. RESULTS: One thousand and eighty-five observations were made, corresponding to 850 patients admitted to the ICUs (16.7%) and internal medicine departments (83.3%). Appropriate antibiotic prescriptions increased by 6.4% between 2013 and 2015. The greatest improvement in appropriate prescriptions was observed for glycopeptides and fluoroquinolones (+17.4% and +16.2%, respectively). We reported 305 inappropriate prescriptions, with the most frequent errors being absence of an infectious process (33.3%), inadequate combination therapy (12.8%), and absence of microbiological investigations (8.5%). A reduced incidence of methicillin-resistant Staphylococcusaureus (MRSA) was also observed (p<0.0037). CONCLUSIONS: Antimicrobial stewardship programs contribute to improving antibiotic prescription and can be implemented in small community hospitals. Narrower interventions, focused on a single disease or single antibiotic should be encouraged.

Epidemiologic trend of pediatric inflammatory bowel disease in Latin America: The Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) Working Group. / Tendencia epidemiológica de la enfermedad intestinal inflamatoria en pacientes pediátricos en América Latina: Grupo de Trabajo en Enfermedad Intestinal Inflamatoria, Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (SLAGHNP).

INTRODUCTION AND OBJECTIVES: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. MATERIALS AND METHODS: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005 to 2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. RESULTS: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn's disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. CONCLUSIONS: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.

DNA barcoding of freshwater ichthyoplankton in the Neotropics as a tool for ecological monitoring.

Quantifying and classifying ichthyoplankton is one of the most effective ways of monitoring the recruitment process in fishes. However, correctly identifying the fish based on morphological characters is extremely difficult, especially in the early stages of development. We examined ichthyoplankton from tributaries and reservoirs along the middle stretch of the Paranapanema River, one of the areas most impacted by hydroelectric projects in the Neotropics. Matching DNA sequences of the COI gene (628-648 bp) allowed us to identify 99.25% of 536 samples of eggs (293) and larvae (243) subjected to BOLD-IDS similarity analysis with a species-level threshold of 1.3%. The results revealed 37 species in 27 genera, 15 families and four orders, some 23.8% of documented fish species in the Paranapanema River. Molecular identification meant that we could include data from egg samples that accounted for about 30% of the species richness observed. The results in this study confirm the efficacy of DNA barcoding in identifying Neotropical ichthyoplankton and show how the data produced provide valuable information for preparing plans for conserving and managing inland waters.

Low-cost self-irrigating bipolar forceps.

A low cost method for providing continuous saline drip in bipolar diathermy is described, which use is adaptable to any type of standard bipolar forceps. The advantages of this system versus commercially available self-irrigating forceps are reported.

Localization accuracy of AC-PC line and functional pallidal target using BRW stereotactic implementation system and axial CT scanning. An experimental study.

BACKGROUND: Ventriculography is still considered an unavoidable step for functional target localization, even though this method is invasive and requires stereotactic rooms, orthogonal frames, and parallax-free X-ray equipment. In this experimental study, the authors investigated the feasibility of performing stereotactic lesions using a conventional, widely employed frame, such as the Brown-Roberts-Wells (BRW) apparatus, and computerized axial tomography (CAT) imaging. METHODS: Five ex vivo models consisting of cadaveric brains enclose in a plastic shell were fixed in a BRW frame. A simple BRW implementation was used to ensure more symmetrical placement of the basal ring. Two-millimeter plastic balls were inserted at the level of the anterior (AC) and posterior commissures (PC) and at the target in the pallidus. Their final position was measured on the anatomical specimens and compared with Schaltenbrand Atlas maps. RESULTS: The error in estimating the length of the intercommissural line ranged from 0.5 mm to 2.0 mm, with a maximum backward angulation of four degrees in predicting the AC-PC plane. Upon dissection, in four out of five cases, the balls were found within the area of the pallidus defined by Laitinen for posteroventral pallidotomy. CONCLUSIONS: The authors conclude that anatomical identification of the AC-PC line and the pallidus target, using the BRW stereotactic system and CAT axial images alone offers sufficient accuracy. They suggest that functional neurosurgery for movement disorders could be safely and successfully carried out without ventriculography if neurophysiological monitoring is also employed.