Viruses that are typically benign sometimes invade the brainstem in otherwise healthy children. We report bi-allelic DBR1 mutations in unrelated patients from different ethnicities, each of whom had brainstem infection due to herpes simplex virus 1 (HSV1), influenza virus, or norovirus. DBR1 encodes the only known RNA lariat debranching enzyme. We show that DBR1 expression is ubiquitous, but strongest in the spinal cord and brainstem. We also show that all DBR1 mutant alleles are severely hypomorphic, in terms of expression and function. The fibroblasts of DBR1-mutated patients contain higher RNA lariat levels than control cells, this difference becoming even more marked during HSV1 infection. Finally, we show that the patients' fibroblasts are highly susceptible to HSV1. RNA lariat accumulation and viral susceptibility are rescued by wild-type DBR1. Autosomal recessive, partial DBR1 deficiency underlies viral infection of the brainstem in humans through the disruption of tissue-specific and cell-intrinsic immunity to viruses.

Health literacy, a more complex concept than knowledge, is a required capacity to obtain, understand, integrate and act on health information [1], in order to enhance individual and community health, which is defined by different levels, according to the autonomy and personal capacitation in decision making [2]. Medium levels of Health literacy in an adolescent population were found in a study conducted in 2013/2014, being higher in sexual and reproductive health and lower in substance use. It was also noticed that the higher levels of health literacy were in the area adolescents refer to have receipt more health information. The health literacy competence with higher scores was communication skills, and the lower scores were in the capacity to analyze factors that influence health. Higher levels were also found in younger teenagers, but in a higher school level, confirming the importance of health education in these age and development stage. Adolescents seek more information in health professionals and parents, being friends more valued as a source information in older adolescents, which enhance the importance of peer education mainly in older adolescents [3]. As a set of competences based on knowledge, health literacy should be developed through education interventions, encompassing the cultural and social context of individuals, since the society, culture and education system where the individual is inserted can define the way the development and enforcement of the health literacy competences [4]. The valued sources of information should be taken into account, as well as needs of information in some topics referred by adolescents in an efficient health education. Schizophrenia is a serious and chronic mental illness which has a profound effect on the health and well-being related with the well-known nature of psychotic symptoms. The exercise has the potential to improve the life of people with schizophrenia improving physical health and alleviating psychiatric symptoms. However, most people with schizophrenia remains sedentary and lack of access to exercise programs are barriers to achieve health benefits. The aim of this study is to evaluate the effect of exercise on I) the type of intervention in mental health, II) in salivary levels of alpha-amylase and cortisol and serum levels of S100B and BDNF, and on III) the quality of life and selfperception of the physical domain of people with schizophrenia. The sample consisted of 31 females in long-term institutions in the Casa de Saúde Rainha Santa Isabel, with age between 25 and 63, and with diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Physical fitness was assessed by the six-minute walk distance test (6MWD). Biological variables were determined by ELISA (Enzyme-Linked Immunosorbent Assay). Psychological variables were assessed using SF-36, PSPP-SCV, RSES and SWLS tests. Walking exercise has a positive impact on physical fitness (6MWD -p = 0.001) and physical components of the psychological test...

Immuno-osseous dysplasia is characterised by spondyloepiphyseal dysplasia, lymphopenia with defective cellular immunity, and progressive renal disease. We describe a patient with a severe form of the disease, review the features of another 24 patients, and discuss the previous classification. The diVerences between the two groups are not striking, and although similarities are greater between aVected sibs, the same diagnosis of Schimke immuno-osseous dysplasia should apply to them all. The aetiology and physiopathology of this rare osteochondrodysplasia of presumed autosomal recessive inheritance remain unknown. (J Med Genet 1999;36:786-789)

Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in the perinatal period. This condition results from a period of ischemia and hypoxia to the brain of neonates, leading to several disorders that profoundly affect the daily life of patients and their families. Currently, therapeutic hypothermia (TH) is the standard of care in developing countries; however, TH is not always effective, especially in severe cases of HIE. Addressing this concern, several preclinical studies assessed the potential of stem cell therapy (SCT) for HIE. With this systematic review, we gathered information included in 58 preclinical studies from the last decade, focusing on the ones using stem cells isolated from the umbilical cord blood, umbilical cord tissue, placenta, and bone marrow. Outstandingly, about 80% of these studies reported a significant improvement of cognitive and/or sensorimotor function, as well as decreased brain damage. These results show the potential of SCT for HIE and the possibility of this therapy, in combination with TH, becoming the next therapeutic approach for HIE. Nonetheless, few preclinical studies assessed the combination of TH and SCT for HIE, and the existent studies show some contradictory results, revealing the need to further explore this line of research.

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination.