Objective:To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.Methods:We collected molecular and clinical data from several diagnostic and research cohorts. Functional consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes.Results:We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families.Conclusions:De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1-associated disorders.

Toxemia da prenhez é considerada um transtorno metabólico de grande impacto econômico na produção de ovinos, porém as particularidades de repercussão sistêmicas deste distúrbio ainda são pouco esclarecedoras. O presente estudo teve por objetivo avaliar o perfil bioquímico e hormonal de 77 ovelhas com diagnóstico clínico de toxemia da penhez e comparar os achados laboratoriais de acordo com a resolução clínica dos animais, alta hospitalar (G1) e aqueles que morreram (G2). A manifestação clinica da doença foi observada no período do pré-parto em 100% dos animais, destes 66,2 % (n=51) receberam alta clínica e 33,8% (n=26) morreram. Dos casos de toxemia da prenhez estudados havia gestação múltipla em 55,8%. Dentre os parâmetros estudados, cortisol, uréia, AST e CK estavam mais elevados no G2 em relação ao G1 com diferenças significativas (P<0,05). Foi encontrado aumento nas concentrações de glicose plasmática, frutosamina, albumina, creatinina, ß-hidroxubutirato, ácido graxo não esterificado e L-lactato, porém não houve diferenças entre os grupos (P>0,05). Não ocorreram alterações nas taxas de colesterol e triglicerídios. Houve redução nos índices da insulina, não havendo diferenças entre G1 e G2 (P>0,05). Todas as ovelhas apresentaram cetonúria e acidúria.

RESUMO.-O objetivo do presente trabalho foi pesquisar a prevalência e a etiologia da mastite bovina na bacia leiteira do município de Rondon do Pará, bem como avaliar o perfil de sensibilidade e resistência dos agentes isolados frente aos antimicrobianos. The prevalence and the etiology of bovine mastitis in the dairy region of the county of Rondon of Pará were investigated. The sensibility and the resistance of the isolated agents to the antimicrobiotics was evaluetad; 237 mixed-bred milk cows were used on nine properties, which were hand milked once a day and kept on Brachiaria brizantha pasture, with supply of mineral salt and water ad libitum. Clinical examination of the mammary gland, the test of the sieve and California Mastitis Test were performed. Of the 935 examined mammary quarters, 6.6% had subclínical mastitis, 1.3% clinical mastitis, and 92.1% were negative. The isolated bacteria in the clinical mastitis were coagulase negative Staphylococcus spp. (25%), Staphylococcus aureus (16.7%), Streptococcus spp. (8,3%), and Corynebacterium spp. (8.3%). In the subclínical mastitis coagulase negative Staphylococcus spp. (32.3%), Staphylococcus aureus (17.7%), Staphylococcus intermedius (1.6%), Streptococcus spp. (4.8%), Corynebacterium spp. (4.8%), and coagulase negative Staphylococcus spp./S.aureus (1.6%) were isolated. There was no microbial growth in 41.7% of the samples with clinical mastitis and in 37.1% with subclínical mastitis. In the antibiogram, 100% of the isolated negative coagulase Staphylococcus spp., S. aureus, S. intermedius, and Streptococcus spp. were sensitive to sulfazotrim. On the other hand, Corynebacterium spp. were 100% resistant to this same antimicrobiotic. Cefalotina, cefoxitina and gentamicina were efficient against the isolated Staphylococcus spp. which represent the greater part of the mastitis agents in this study. Mastitis was diagnosed in all flocks studied, however the number of affected animals was considered low; this probably is due to low milk production of the cows and to permanence of the calf with the mother after milking, what favors emptying the mammary gland. But hygienic sanitary measures and management practices have to be improved.

In order to evaluate the clinical-laboratorial alterations, six Nellore calves were inoculated with 10 7 Trypanosoma vivax isolated from Poconé region, Mato Grosso, Brazil. The animals were evaluated daily for rectal temperature, packed cell volume (PCV), parasitemia, antibody production, color of mucous membranes, behavior and appetite. Blood and serum samples for biochemical evaluation for aspartate aminotransferase (AST), alkaline phosphatase (AF), gamma glutamyltransferase (GGT), cholesterol, urea, creatinine, creatine kinase (CK), calcium, phosphorus and proteinogram were collected on days 4, 8, 12, 16, 23 and 30 post inoculation (DPI). During the following 6 months rectal temperature, PCV and parasitemia were evaluated weekly. T. vivax was evidenced from 1 DPI in all calves and persisted until day 30 in five of six animals. A remarkable decrease (p<0.05) of PCV mean value (25%) was observed on 10 DPI. The animals presented no alterations in their clinical or serum biochemical state during the trial. Seroconversion took place 6 and 8 DPI, and all the animals remained seropositive during the 30 days of experiment. In all the experimental animals the occurrence of T. vivax infection was verified, characterized by the increase of corporal temperature, presence of the blood protozoa and reduction of the globular volume, without alterations in the other variables analyzed. Nellore calves, when experimentally inoculated with T. vivax, are able to establish a balance between host-parasite relationship.

, 20 e 10 dias antes do parto, no momento do parto e nos 10, 20 e 30 dias pós-parto. As variáveis mensuradas foram: glicose, frutosamina, ácidos graxos não esterificados (AGNEs), β-hidroxibutirato, colesterol, triglicérides, proteína total, albumina, ureia e pesquisa de corpos cetônicos na urina. As determinações hormonais foram cortisol e a insulina. No fluido ruminal foi determinado o pH e a concentração dos ácidos graxos voláteis. Na análise estatística foi empregada a ANOVA e estudo de correlação (P<0,05). A monensina elevou (P<0,05) a concentração do propionato no rúmen e frutosamina e insulina no sangue. A administração da monensina promoveu melhora em alguns indicadores do balanço energético. Palavras-chave: ácidos graxos voláteis; ionóforo; ovinos; perfil energético; perfil proteico. AbstractThe study was carried out to analyze the effect of monensin supplementation during 60 days prior to parturition, and 30 days postpartum, on the metabolic and hormonal profile of ewes. Pregnant ewes (n=13) were randomly divided into two groups: monensin group (n = 7; 30 mg/day) and control group (n = 6). Blood and ruminal fluid samples were collected 60, 50,40,30,20 and 10 days prior to parturition, at the time of parturition and on 10, 20 and 30 days postpartum. The following variables were analyzed: glucose, fructosamine, non-esterfied fatty acids, β-hydroxybutyrate, cholesterol, triglycerides, total protein, albumin, urea and ketone bodies in the urine. The hormonal determinations were cortisol and insulin. The analysis of the ruminal fluid involved pH and concentration of volatile fatty acids. The statistical analysis involved ANOVA and correlation studies (P<0,05). Monensin increased (P<0,05) the propionic acid concentration in the rumen and blood fructosamine and insulin. The administration of monensin improved some indicators of energy balance.

Unilateral selective thalamic-cortical disconnection is a common feature in our patients and is associated with both a focal pattern of CSWS and a pathological type of frequency-dependent excitability (peak: 10-20Hz). We propose that this excitability represents an abnormal synaptic plasticity previously described as the augmenting response. This synaptic plasticity has been described as absent in the corticocortical interactions in healthy experimental animals, emerging after ablation of the thalamus and producing a frequency-dependent potentiation with a peak at 10-20Hz. Because this response is potentiated by sleep states of reduced brainstem activation and by appropriate stimulating rhythms, such as sleep spindles, the simultaneous occurrence of these two factors in nonrapid-eye-movement sleep is proposed as an explanation for CSWS in our patients.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.

RESUMO.-Apesar de forragens grosseiras e secas serem empregadas comumente na alimentação de vacas em vá-rias regiões, especialmente durante o período seco, a compactação primária do abomaso tem sido pouco relatada no Brasil, provavelmente pela dificuldade de diagnóstico dos veterinários de campo. Este trabalho objetivou realizar um estudo retrospectivo sobre a compactação primária do abomaso em 14 bovinos no Estado de Pernambuco. Oito casos considerados moderados, sem grave distensão abdominal e sem compactação do rúmen, foram tratados conservativamente e quatro casos graves, com severa distensão abdominal e compactação do rúmen, foram tratados cirurgicamente. Um touro foi encaminhado para abate e uma vaca morreu antes de receber qualquer tratamento. O maior número de casos de compactação do abomaso ocorreu em bovinos da raça Holandesa com seis casos (42,9%), seguido por animais mestiços com cinco casos (35,8%) e as raças Pardo-Suiça, Nelore e Marchigiana com um caso cada (21,3% Despite the frequent use of dry and fibrous roughage for feeding cows in many regions, especially during the dry season, impaction of the abomasum has been poorly reported in Brazil, probably because the condition is misdiagnosed by practitioners. The present paper aimed to accomplish a retrospective study on primary abomasal impaction in 14 cattle from Pernambuco State, northeastern Brazil. Eight moderate cases, without severe abdominal distention and with no rumen compaction, were treated conservatively, and four severe cases, with severe abdominal distention and rumen compaction, were treated surgically. One bull was slaughtered and one cow died without treatment. The greater number of abomasal impaction cases was in Holstein cows with six cases (42.9%), followed by crossbred cattle with five cases (35.8%), and the breeds Brown-Swiss, Nelore and Marchigiana, each with one case (21.3%). The food composition was characterized by low quality fibers and varied greatly among cases. Most frequent clinical signs were apathy, dehydration, hypomotility and ruminal bloat, intestinal hypomotility and scanty or absent feces with mucus. The hematological findings revealed leukocytosis with neutrophilia and hyperfibrinogenemia in most cases. Ruminal fluid analysis showed compromised flora and fauna dynamics and increased chlorine ion concentration. Clinical (4/8) and chirurgical (2/4) recovery rate achieved 50%. The clinical and chirurgical methods remain as viable options for the treatment of light and severe impaction, but the prognosis is always reserved especially when associated to late pregnancy.