Hospital Universitário de Brasília

Some oral manifestations have been observed in patients with coronavirus disease 2019 (COVID-19). However, there is still a question about whether these lesions are due to coronavirus infection or secondary manifestations resulting from the patient's systemic condition. Thus, this article aims to report an additional case of an oral condition in a patient diagnosed with COVID-19. Our patient, a sixty-seven-year-old Caucasian man, tested positive to coronavirus and presented oral manifestations such as recurrent herpes simplex, candidiasis, and geographic tongue. We support the argument that some oral conditions could be secondary to the deterioration of systemic health or due to treatments for COVID-19. The present case report highlights the importance of including dentists in the intensive care unit multi-professional team to improve oral health in critical patients, not only COVID-19 patients, but also, to contribute to evidence-based and decision-making in managing infectious diseases.

Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that have the unique function of terminating cyclic nucleotide signaling by catalyzing the hydrolysis of cAMP and GMP. They are critical regulators of the intracellular concentrations of cAMP and cGMP as well as of their signaling pathways and downstream biological effects. PDEs have been exploited pharmacologically for more than half a century, and some of the most successful drugs worldwide today affect PDE function. Recently, mutations in PDE genes have been identified as causative of certain human genetic diseases; even more recently, functional variants of PDE genes have been suggested to play a potential role in predisposition to tumors and/or cancer, especially in cAMP-sensitive tissues. Mouse models have been developed that point to wide developmental effects of PDEs from heart function to reproduction, to tumors, and beyond. This review brings together knowledge from a variety of disciplines (biochemistry and pharmacology, oncology, endocrinology, and reproductive sciences) with emphasis on recent research on PDEs, how PDEs affect cAMP and cGMP signaling in health and disease, and what pharmacological exploitations of PDEs may be useful in modulating cyclic nucleotide signaling in a way that prevents or treats certain human diseases.

CONTEXT: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. OBJECTIVE: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. DESIGN AND SETTING: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. PATIENTS OR OTHER PARTICIPANTS: 345 probands, 18 family members, and 292 controls were studied. INTERVENTION: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. MAIN OUTCOME MEASURE: Rare sequence variants in TAC3/TACR3 were detected. RESULTS: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. CONCLUSIONS: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.

INTRODUCTION: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. METHODS: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. RESULTS: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. CONCLUSIONS: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

Selective luteinizing hormone deficiency due to mutations in the luteinizing hormone beta-subunit gene (LHB) is a rare cause of hypogonadism. We describe the clinical features of a consanguineous family in which three siblings, two men and one woman, had hypogonadism related to isolated luteinizing hormone deficiency. These subjects have a newly discovered homozygous mutation of a 5 splice site in LHB: IVS2+1GC. This mutation disrupts the splicing of messenger RNA (mRNA), generating a gross abnormality in the processing of the luteinizing hormone beta-subunit mRNA, which abrogates the secretion of luteinizing hormone. We also determined that the female phenotype of this LHB mutation is characterized by normal pubertal development, secondary amenorrhea, and infertility. L uteinizing hormone plays an essential role in normal pubertal development and reproductive function in humans. It consists of two glycosylated, noncovalently linked subunits: a hormone-specific beta subunit and an alpha subunit common to all members of the glycoprotein hormone family. Selective luteinizing hormone deficiency is predicted to compromise reproductive capacity markedly in both sexes. 1,2 Inactivating mutations of the human luteinizing hormone beta-subunit gene (LHB) were previously described in three men with hypogonadism who had normal genitalia at birth but had no pubertal development and had infertility due to selective luteinizing hormone deficiency. [3] 4][5] To our knowledge, no female phenotype of such inactivating mutations in the LHB gene has been described. We describe the clinical and hormonal characteristics of three siblings, two men and a woman, all of whom had hypogonadism associated with a newly discovered mutation of the LHB gene. c a se r ep or t S

AIM: To determine in vitro the antimicrobial activity of Fill Canal, Sealapex, Mineral Trioxide Aggregate (MTA), Portland cement and EndoRez on various species of microorganisms. METHODOLOGY: The diffusion method on Müller-Hinton agar (MH) was employed. A base layer was made using MH agar and five wells were made by removing agar at equidistant points. Sealers were placed into the wells immediately after manipulation. The microorganisms Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Pseudomonas aeruginosa ATCC 27853 and Candida albicans ATCC 10231 were seeded by pour plate. The plates were kept at room temperature for 2 h for prediffusion and then incubated at 37 degrees C for 24 h. Aliquots of 10 mL of 0.05% triphenyltetrazolium chloride gel were added for optimization and the zones of inhibition were measured. RESULTS: Sealapex and Fill Canal demonstrated antimicrobial activity for all strains. For MTA and Portland cement, only E. coli was not inhibited. No antimicrobial activity was detected for EndoRez. CONCLUSIONS: In this laboratory study, Fill Canal, Sealapex, MTA and Portland cement presented antimicrobial activity whilst EndoRez did not.

BACKGROUND: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). METHODS: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

BACKGROUND: We validated the new European Organisation for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN43). METHODS: We enrolled 812 patients with head and neck cancer from 18 countries. Group 1 completed the questionnaire before therapy, and 3 and 6 months later. In group 2 (survivors), we determined test-retest reliability using intraclass correlation coefficients (ICC). Internal consistency was assessed using Cronbach's Alpha, the scale structure with confirmatory factor analysis, and discriminant validity with known-group comparisons. RESULTS: Cronbach's alpha was >0.70 in 10 of the 12 multi-item scales. All standardized factor loadings exceeded 0.40. The ICC was >0.70 in all but two scales. Differences in scale scores between known-groups were >10 points in 17 of the 19 scales. Sensitivity to change was found to be sufficient in 18 scales. CONCLUSIONS: Evidence supports the reliability and validity of the EORTC QLQ-HN43 as a measure of quality of life.

The purpose of this retrospective study was to determine the prevalence of hypodontia and associated dental anomalies in patients undergoing orthodontic treatment in Brasília, Brazil, over a 2 year period (1998-2000). The records of 1049 orthodontic patients between 10 and 15.7 years of age (507 males and 542 females) from 16 orthodontic clinics were analysed. Descriptive statistics were performed for the study variables. A chi-square test was used to determine the difference in the prevalence of hypodontia between genders. The prevalence of hypodontia was 6.3 per cent (39.4 per cent males and 60.6 per cent females) with no statistically significant difference between the genders. One case of oligodontia was observed. The maxillary lateral incisor was the most frequently missing tooth, followed by the mandibular second premolar. All cases of hypodontia, except one, were associated with at least one other dental anomaly. These associated dental anomalies were retained primary teeth (30.3 per cent), ectopic canine eruption (25.8 per cent), taurodontism (21.2 per cent), and peg-shaped maxillary lateral incisors (16.7 per cent).

The treatments of choice in Alzheimer's disease (AD) are cholinesterase inhibitors and NMDA-receptor antagonists, although doubts remain about the therapeutic effectiveness of these drugs. Herbal medicine products have been used in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD) but with various responses. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly. Randomized controlled studies assessing AD in individuals older than 65 years were identified through searches of MEDLINE, LILACS, Cochrane Library, dissertation Abstract (USA), ADEAR (Alzheimer's Disease Clinical Trials Database), National Research Register, Current Controlled trials, Centerwatch Trials Database and PsychINFO Journal Articles. The search combined the terms Alzheimer disease, dementia, cognition disorders, Herbal, Phytotherapy. The crossover results were evaluated by the Jadad's measurement scale. The systematic review identified two herbs and herbal formulations with therapeutic effects for the treatment of AD: Melissa officinalis, Salvia officinalis and Yi-Gan San and BDW (Ba Wei Di Huang Wan). Ginkgo biloba was identified in a meta-analysis study. All five herbs are useful for cognitive impairment of AD. M. officinalis and Yi-Gan San are also useful in agitation, for they have sedative effects. These herbs and formulations have demonstrated good therapeutic effectiveness but these results need to be compared with those of traditional drugs. Further large multicenter studies should be conducted in order to test the cost-effectiveness of these herbs for AD and the impact in the control of cognitive deterioration.

Multinodular and vacuolating neuronal tumor of the cerebrum is a recently reported benign, mixed glial neuronal lesion that is included in the 2016 updated World Health Organization classification of brain neoplasms as a unique cytoarchitectural pattern of gangliocytoma. We report 33 cases of presumed multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a remarkably similar pattern of imaging findings consisting of a subcortical cluster of nodular lesions located on the inner surface of an otherwise normal-appearing cortex, principally within the deep cortical ribbon and superficial subcortical white matter, which is hyperintense on FLAIR. Only 4 of our cases are biopsy-proven because most were asymptomatic and incidentally discovered. The remaining were followed for a minimum of 24 months (mean, 3 years) without interval change. We demonstrate that these are benign, nonaggressive lesions that do not require biopsy in asymptomatic patients and behave more like a malformative process than a true neoplasm.

OBJECTIVES: To verify radiomorphometric indices and fractal dimension (FD) in dental panoramic radiographs (DPRs) of children with different types of osteogenesis imperfecta (OI) and also to verify the effect of pamidronate (PAM) treatment in such panoramic analyses. METHODS: In this retrospective study, 197 DPRs of 62 children with OI Types I, III and IV who were in treatment with a comparable dosage of intravenous PAM were selected. The mandibular cortical width (MCW), mandibular cortical index, visual estimation of the cortical width and FD of three standardized trabecular and cortical mandibular regions of interest were obtained from the radiographs. Factorial analysis of variance and Fisher test were used to compare FD and MCW measurements in children with different types of OI for different PAM cycles. RESULTS: Children with all types of OI have thinner and more porous mandibular cortices at the beginning of treatment. There were significant differences between MCW and FD of the cortical bone, regarding different types of OI and number of PAM cycles (p = 0.037 and p = 0.044, respectively). FD measurements of the trabecular bone were not statistically different among OI types nor were PAM cycles (p > 0.05). CONCLUSIONS: Children with OI presented cortical bone alterations after PAM treatment. Both MCW and the FD of the cortical bone were higher in children with OI after PAM treatment. It is argued that cortical bone should be considered for analyzing patients with OI, as well as to monitor the progress of PAM treatment.

"O objetivo deste estudo foi o de identificar e analisar acidentes e as cargas de trabalho a que estão expostos os trabalhadores de enfermagem no desenvolvimento de suas atividades. Trata-se de um estudo de caso, do tipo descritivo e exploratório, desenvolvido em um hospital de ensino do Distrito Federal. Foi realizado levantamento dos acidentes de trabalho registrados no SESMT e CCIH no período de janeiro de 1998 a dezembro de 2002 e identificadas essas cargas de trabalho. Constatou-se que os trabalhadores sofreram 76 acidentes de trabalho, dentre quais, 83,95% foram causados por materiais perfurocortantes, 8,64% por quedas, 6,17% por exposições a fluidos biológicos e 1,24% por contusões. A diversidade e simultaneidade de cargas de trabalho contribuíram para a ocorrência desses acidentes."

Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.

A 35-year-old previously healthy female presented with fever, cough, sneezing, rhinorrhea, diarrhea, myalgia, anosmia, and hypogeusia. She was diagnosed with mild coronavirus disease 2019 (COVID-19) infection (positive quantitative reverse transcription polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] performed by nasopharyngeal swab) and did not require hospitalization. After 10 days, she recovered from respiratory symptoms but developed paresthesia and difficulty in moving her right arm. After 1 day, she became unable to move the right arm and developed a lower voice tone, generalized rigidity, and slowness of movement with gait unsteadiness. Two weeks after the onset of neurological symptoms, physical examination revealed decreased facial expression, eyelid retraction, and slow and hypometric saccades as well as hypophonia. She also had generalized and asymmetric (right worse than the left) bradykinesia and cogwheel rigidity, stooped posture, gait with reduced arm swing, en bloc turning, and decreased stride length. The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score on the first evaluation was 49. After 4 days of therapy with 200/50 mg of levodopa/benserazide three times a day, there was significant improvement of facial expression, dysarthria, bradykinesia, and arm swinging. The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score decreased to 32 (see the Supplementary Information for Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III detailed description; physical examination features are shown in Video S1). Cognition was normal, and Sniffin' Sticks confirmed moderate hyposmia (9/16 correct answers). The proband had no family history of parkinsonism. Laboratory workup included a normal cerebrospinal fluid analysis (cells, 0; protein, 36 mg/dL; glucose, 60 mg/dL). The 3-Tesla magnetic resonance imaging was unremarkable, including an evaluation of nigrosome-1 and neuromelanin imaging. Brain fluorodeoxyglucose–positron emission tomography showed normal glucose metabolism. There was decreased dopamine transporter density on the left putamen (more evident in the mid-putamen, different from the posterior involvement usual of idiopathic Parkinson's disease). Such finding contrasted with the patient's bilateral symptoms, what could be attributed to microstructural changes in other brain pathways (Fig. 1). Our patient clearly has akinetic-rigid parkinsonism. The abnormal dopamine transporter scan and levodopa improvement confirm the presynaptic nature of the parkinsonian syndrome. As the patient was neurologically normal prior to the COVID-19 infection, we conclude that SARS-CoV-2 infection is responsible for the parkinsonism. Méndez-Guerrero and colleagues1 recently described another case of parkinsonism associated with COVID-19 affecting a critically ill patient with pleomorphic neurologic symptomatology. Neurologic manifestations in COVID-19 most commonly described include headache, seizures, stroke, hyposmia, and altered mental status.2, 3 As they may occur regardless of respiratory symptoms, most likely there is direct viral neurotoxicity.4 Since the outbreak of encephalitis lethargica in the 1920s,5 an ever-growing number of viruses have been implicated in postencephalitic parkinsonism, including influenza, Epstein-Barr, West Nile, and Japanese encephalitis.6 In contrast, the COVID-19 clinical and laboratory pictures of our patient do not suggest she had encephalitis. In parkinsonism associated with viral infections, neuropathology varies from direct acute infection to postinfectious neuroinflammation, both culminating with dopaminergic cell loss. SARS-CoV-2 might infect neurons in the central nervous system through either retrograde axonal transport or hematogenic routes.4 Our patient probably had a direct SARS-CoV-2 lesion of the nigro-striatal system.7 In conclusion, we report a case of levodopa-responsive parkinsonism probably caused by direct SARS-CoV-2 infection, broadening the disease clinical spectrum. We thank Dr. Alaor Barra Sobrinho, Director of Imagens Médicas de Brasilia, for kindly giving support for nuclear medicine complementary exams. (1) Research Project: A. Conception, B. Organization; (2) Manuscript: A. Writing of the First Draft, B. Review and Critique. I.F.: 1A, 1B, 1C, 2A, 2B P.P.B.: 1A, 1B, 1C, 2A, 2B F..M.: 1B, 1C, 2B D..D.CB.: 1B, 1C, 2B F.B.M.: 1B, 1C, 2B F.C.: 1A 2B Ingrid Faber: research support from Sabin Laboratory. Pedro Renato P. Brandão: research support from Sabin Laboratory. Fiorella Menegatti: none. Diógenes Diego de Carvalho Bispo: none. Fernando Bisinoto Maluf: none Francisco Cardoso: none Table S1.Unified Parkinson's Disease Rating Scale Part III before and after levodopa Video S1. Supporting information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.

BACKGROUND: Group A Streptococcus (GAS) clinical and molecular epidemiology varies with location and time. These differences are not or are poorly understood. METHODS AND FINDINGS: We prospectively studied the epidemiology of GAS infections among children in outpatient hospital clinics in Brussels (Belgium) and Brasília (Brazil). Clinical questionnaires were filled out and microbiological sampling was performed. GAS isolates were emm-typed according to the Center for Disease Control protocol. emm pattern was predicted for each isolate. 334 GAS isolates were recovered from 706 children. Skin infections were frequent in Brasília (48% of the GAS infections), whereas pharyngitis were predominant (88%) in Brussels. The mean age of children with GAS pharyngitis in Brussels was lower than in Brasília (65/92 months, p<0.001). emm-typing revealed striking differences between Brazilian and Belgian GAS isolates. While 20 distinct emm-types were identified among 200 Belgian isolates, 48 were found among 128 Brazilian isolates. Belgian isolates belong mainly to emm pattern A-C (55%) and E (42.5%) while emm pattern E (51.5%) and D (36%) were predominant in Brasília. In Brasília, emm pattern D isolates were recovered from 18.5% of the pharyngitis, although this emm pattern is supposed to have a skin tropism. By contrast, A-C pattern isolates were infrequently recovered in a region where rheumatic fever is still highly prevalent. CONCLUSIONS: Epidemiologic features of GAS from a pediatric population were very different in an industrialised country and a low incomes region, not only in term of clinical presentation, but also in terms of genetic diversity and distribution of emm patterns. These differences should be taken into account for designing treatment guidelines and vaccine strategies.

OBJECTIVE: To investigate the association between institutional violence in obstetrics and postpartum depression (PP depression) and the potential effect of race, age, and educational level in this outcome. METHODS: This is a cross-sectional study about the health care conditions for the maternal and child population of the Federal District, Brazil, carried out in 2011. The study has used a probabilistic sample of 432 women, whose children were aged up to three months, stratified by clusters. Indicators of institutional violence and demographic characteristics have been used in a logistic regression model to estimate the probability of occurrence of postpartum depression. RESULTS: The model has identified a high prevalence of postpartum depression, being it higher among non-white women and adolescent females, besides having a strong positive association between the several indicators of obstetric violence and postpartum depression. Positive interactions on a multiplicative scale have also been observed between: violence by negligence by health care professionals and race and age; physical violence from health care professionals and age; and, verbal violence from health care professionals and race. CONCLUSIONS: The indicators adopted to reflect institutional violence in obstetric care are positively associated with postpartum depression, which calls for a reflection on the need to make the health care protocols adequate to the precepts of the Brazilian humanization of childbirth care policies and changes in the obstetric care model.

CONTEXT: Selenoproteins are essential for life, and their biosynthesis requires the incorporation of the rare amino acid selenocysteine (Sec) in a process mediated by the Sec insertion sequence-binding protein 2 (SBP2). Although SBP2 is considered a rate-limiting factor mediating Sec incorporation, there has been little evidence so far linking SBP2 dysfunction to widespread selenoprotein-related disease. OBJECTIVE: The objective of the study was to report the discovery of novel truncation mutations in the SBP2 gene (R120X/R770X) in a female adolescent and the clinical consequences of the combined deficiency of selenoproteins. SUBJECTS AND METHODS: A 12-yr-old girl who presented with a syndrome of abnormal thyroid hormone metabolism, delayed bone maturation, congenital myopathy, and impaired mental and motor coordination development and her family were studied. The coding region of the SBP2 gene was analyzed by sequencing, and gel shift assays were performed to address the in vitro binding properties of the mutant SBP2 protein. RESULTS: Serum levels of selenium and glutathione peroxidase in the proband were reduced, and selenoprotein P levels were undetectable. DNA sequencing of the SBP2 gene revealed a compound heterozygous mutation (R120X/R770X). The R120X mutation disrupted all functional motifs and the R770X inhibited the binding of SBP2 to Sec insertion sequence elements. Interestingly, selenium supplementation normalized serum selenium and glutathione peroxidase but not selenoprotein P levels and did not restore thyroid hormone metabolism dysfunction. CONCLUSIONS: This distinctive phenotype can only be explained by the combined deficiency of functionally important selenoproteins and pinpoints the clinical relevance of selenoproteins and selenium economy in human development.