Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: Beyond neurodevelopmental disorders and epilepsy.

Neurodevelopmental disorders have been linked to numerous genes, particularly pathogenic variants in genes encoding postsynaptic scaffolding proteins, like SHANK3. This study aims to provide insights into the cardiovascular profile of patients with pathogenic SHANK3 variants, expanding beyond the well-established associations with neurodevelopmental disorders and epilepsy. We conducted a prospective study involving patients affected by neurodevelopmental disorders with pathogenic SHANK3 variants. Comprehensive cardiovascular assessments were performed and molecular genetic testing included chromosomal microarray followed by clinical exome sequencing. We identified five patients with de novo SHANK3 variants, all of whom exhibited cardiac involvement, including myocardial dysfunction, congenital heart disease (patent ductus arteriosus), and a case of postictal atrial fibrillation. Our findings emphasize an elevated risk of cardiovascular abnormalities in patients with SHANK3 pathogenic variants compared to prior reports. Despite their young age, these patients displayed significant cardiac abnormalities. The study highlights the necessity of integrating cardiac evaluation and ongoing cardiovascular monitoring into multidisciplinary care, facilitating early detection of heart failure and assessment of the risk of sudden unexpected death in epilepsy (SUDEP). Further research is needed to elucidate the underlying mechanisms of cardiac manifestations in SHANK3 mutation carriers.

Cognitive outcome after stereo-electroencephalography-guided radiofrequency thermocoagulation in temporal lobe epilepsy.

OBJECTIVE: Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) is being used incrementally in the invasive diagnosis of epilepsy. There is currently a lack of information regarding the potential cognitive consequences of the extended use of this technique. This work describes, for the first time, the cognitive outcomes after RFTC in patients with temporal lobe epilepsy (TLE), evaluated longitudinally and using a control group. METHODS: Forty-eight adult patients with drug-resistant unilateral TLE (30 RFTC-treated patients and 18 controls) were evaluated using a comprehensive neuropsychological protocol at baseline. In the RFTC group, two follow-up assessments were performed at 3 months and 1 year. The control group was reevaluated after 1 year. Two analyses were performed: 1) group-level analyses, in which linear mixed models were applied according to TLE lateralization (intragroup and intergroup [RFTC vs control] comparisons), and 2) individual-level analyses, in which the Reliable Change Index (RCI) algorithm was developed and a 90% CI (cutoff ± 1.64) was used to describe neuropsychological outcomes at 1 year post-RFTC. A memory subanalysis was performed in hippocampal RFTC patients (25/30). A Spearman coefficient study was conducted to determine the correlation between cognitive change and thermocoagulated contacts. RESULTS: Left- and right-sided TLE patients treated with RFTC showed cognitive preservation at baseline. At a group level, the short-term evaluation, including verbal and visual memory, language, and executive functions, showed preservation in these domains and no significant differences compared with baseline. In the long-term follow-up assessment (1 year after RFTC), no significant intragroup changes were found, nor were significant changes found in comparison with the control group. The RCI algorithm showed that significant individual cognitive losses and gains were infrequent. Three patients presented with naming deficits, only 1 (3.3%) of whom showed a clinically significant deficit. Significant gains were more prevalent in executive function tests with a speed component (4/20 left-sided RFTC patients). Twenty-five of the 30 (83%) patients were treated with hippocampal RFTC. No patients experienced significant loss in verbal delayed memory in the left-sided RFTC sample or in visual delayed memory in the right-sided RFTC sample. The correlations between cognitive change and RFTC contacts were mostly nonsignificant. CONCLUSIONS: In the group-level comparisons, discernible cognitive impairment following RFTC was not evidenced. The majority of patients did not exhibit significant individual declines during the 1-year follow-up period. Notably, the procedural intervention yielded no substantial repercussions on memory functioning following hippocampal RFTC. These findings underscore the evidence supporting the cognitive preservation associated with SEEG-guided RFTC.

Discrimination and dental students: What is the reality in Brazilian institutions?

INTRODUCTION: This study aimed to evaluate whether there is discrimination in the dental educational environment, assess the main reasons for the discriminatory events, and if there is an association between discriminatory episodes and sociodemographic characteristics of undergraduate dental students. MATERIALS AND METHODS: This observational cross-sectional study was conducted with a self-administered questionnaire to students enrolled in three Brazilian dental schools. Questions included sociodemographic characteristics and the occurrence of discriminatory episodes in the dental academic environment. Descriptive analysis was performed in RStudio 1.3 (R Core Team, RStudio, Inc., Boston, USA) software and the associations were tested using Pearson's chi-square test, considering 95% confidence intervals. RESULTS: A total of 732 dental students were included, with a response rate of 70.2%. The vast majority of students were female (66.9%), with white/yellow skin colour (67.9%), and with a mean age of 22.6 (SD 4.1) years. Sixth-eight percent of students reported having experienced some discrimination in the academic environment and most reported feeling uncomfortable with the episode. The main reasons to have been discriminated against raised by students were specific behaviour/habit, have specific moral, ethical, and aesthetic values, gender, and socioeconomic status or social class. The occurrence of discriminatory episodes was associated with female gender (p = .05), non-heterosexual sexual orientation (p < .001), studying in public institutions (p < .001), receiving an institutional scholarship (p = .018), and being in the final undergraduate cycle (p < .001). CONCLUSION: The occurrence of discriminatory episodes was common in Brazilian dental higher education. Discriminatory situations generate traumas and psychological marks, causing a loss of diversity within the academic environment that leads to loss of productivity, creativity, and innovation. Thus, strong institutional policies against discrimination are crucial to create a healthy dental academic environment.

Discriminatory episodes negatively impact the quality of life of Brazilian dental students: A cross-sectional study.

PURPOSE: This study aimed to evaluate whether discriminatory episodes occurring in the university environment were associated with dental students' self-perceived overall quality of life and assess the cumulative effect of perceived discriminatory experiences on the overall quality of life. METHODS: In this cross-sectional study, all students enrolled in three Brazilian dental schools were invited to participate in a survey between August and October 2019. The outcome was students' self-perceived quality of life, measured through the overall quality of life item of the World Health Organization-Quality of Life Abbreviated Version (WHOQOL-BREF). Descriptive, bivariate, and multivariable logistic regression analyses (95% confidence intervals and α of 5%) were conducted using RStudio software. RESULTS: The sample was composed of 732 students (70.2% response rate). The great part was female (66.9%), white or yellow skin color (67.9%), and were children of highly educated mothers. About 68% of the students reported having experienced at least one of the seven discriminatory experiences presented in the questionnaire and 18.1% reported neutral or negative quality of life. In multivariable analyses, it was estimated that students who experienced at least one episode of discrimination were 2.54 times (95% CI: 1.47-4.34) more likely to report worse quality of life than their counterparts who reported no experience of discrimination. There was also a 25% (95% CI: 1.10-1.42) increase in the odds of reporting poorer quality of life for each additional discriminatory experience reported. CONCLUSION: Reporting at least one discriminatory situation in the academic environment was associated with worse quality of life among dental students, and a cumulative effect was also noted.

Evaluation of parasite contamination on toothbrushes in children in Southeastern Brazil / Evaluación de la contaminación parasitaria en cepillos de dientes en niños del sudeste de Brasil

ABSTRACT Introduction : The toothbrush is an important object for the hygiene of the oral cavity and an effective mechanism to remove the oral waste. Objective : To evaluate the perception of care, storage and parasitic contamination of toothbrushes in children with special health care needs (CSHCN) and children without special health care needs (CWSHCN) in Southern of Minas Gerais State. Material and Methods : This is an observational cross-sectional non-randomized study. The population consisted in 54 children, with age between 7 and 14 years. The questionnaire was distributed to patients to evaluate the perception of care and storage of children's toothbrushes. Investigation of toothbrushes contamination was performed by parasitological examination and real-time polymerase chain reactions. Results : Regarding the procedures performed after brushing, 50.0% of children with special health care needs (CSHCN) and 56.3% of children without special health care needs (CWSHCN) report washing their brush bristles with water (p <0.001). Both groups did not use an antiseptic solution on toothbrushes. 73.3% of (CSHCN) and 58.7% of (CWSHCN) answered that they use some protection (brush holder and bathroom cabinet) to avoid exposure of brushes to the environment (p <0.001). Conclusion : The children investigated by the study presented good conditions of care and storage of their toothbrushes. No contamination by pathogenic parasites was found during the study period.

RESUMEN Introducción : El cepillo de dientes es un objeto importante para la higiene de la cavidad bucal y un mecanismo eficaz para eliminar los residuos bucales. Objetivo : Evaluar la percepción del cuidado, almacenamiento y contaminación parasitaria de los cepillos dentales en niños con necesidades especiales de salud (CSHCN) y niños sin necesidades especiales de salud (CWSHCN) en el sur del estado de Minas Gerais. Material y Métodos : Se trata de un estudio observacional transversal no aleatorio. La población consistió en 54 niños, con edad entre 7 y 14 años. El cuestionario fue distribuido a los pacientes para evaluar la percepción del cuidado y almacenamiento de los cepillos dentales de los niños. La investigación de la contaminación de los cepillos dentales se realizó mediante un examen parasitológico y reacciones en cadena de la polimerasa en tiempo real. Resultados : En cuanto a los procedimientos realizados tras el cepillado, el 50,0% de los niños con necesidades especiales de atención sanitaria (NCNEAS) y el 56,3% de los niños sin necesidades especiales de atención sanitaria (NSNEAS) refieren lavar las cerdas del cepillo con agua (p <0,001). Ambos grupos no utilizaron una solución antiséptica en los cepillos de dientes. El 73,3% de los (NCNEAS) y el 58,7% de los (NSNEAS) contestaron que utilizan alguna protección (portacepillos y mueble de baño) para evitar la exposición de los cepillos al medio ambiente (p <0,001). Conclusiones : Los niños investigados por el estudio presentaron buenas condiciones de cuidado y almacenamiento de sus cepillos dentales. No se encontró contaminación por parásitos patógenos durante el período de estudio.

Use of P-CPQ to measure the impact of oral health on the quality of life of children with special health care needs / Uso de la P-CPQ para medir el impacto de la salud oral en la calidad de vida de los niños con necesidades especiales de atención médica / Uso do P-CPQ para mensuração do impacto da saúde bucal na qualidade de vida de crianças com necessidades especiais de saúde

Abstract Introduction and objective: the WHO defined the concept of quality of life as the self-perception that the individual has about his position in the social, cultural and ideological context, being these factors the main responsible for denoting the worst parameters regarding oral health care during the dental clinical examination performed by the dentist. To evaluate the impact of oral health on the quality of life of children with special health care needs aged 7 to 14 years old and the influence of different types of specialties on the quality of life, in the view of parents/caregivers in the Brazil southeast region. Materials and methods: the sample was composed of 62 children enrolled in municipal public schools and the Association of Parents and Friends of the Exceptional. The validated Parental- Caregivers Perception Questionnaire (P-CPQ) was used as an instrument for data collection, applied in the home environment and answered by the main responsible. The relation between demographic factors, type of special need and P-CPQ was evaluated with alpha of 0.05. Results: the worst parameters in Family Impact Scale were observed when the mother and father was responsible for data transmission (p= 0.004). Oral health was associated with the worst parameters of oral symptoms on quality of life in the view of parents (p = 0.012). There was no statistically significant difference regarding the impact of the child's type of specialty on quality of life. Conclusion: the variables caregiver and oral health status child are related to the worst indicators regarding the impact of oral health on quality of life.

Resumen Introducción y objetivo: la OMS definió el concepto de calidad de vida como la autopercepción que tiene el individuo sobre su posición en el contexto social, cultural e ideológico, siendo estos factores los principales responsables de denotar los peores parámetros en cuanto al cuidado de la salud bucal durante el examen clínico dental realizado por el dentista. Evaluar el impacto de la salud bucal en la calidad de vida de los niños con necesidades especiales de atención de la salud de 7 a 14 años de edad y la influencia de los diferentes tipos de especialidades en la calidad de vida, en opinión de los padres/cuidadores de la región sudoriental del Brasil. Materiales y métodos: la muestra se compuso de 62 niños matriculados en escuelas públicas municipales y en la Asociación de Padres y Amigos de los Excepcionales. Se utilizó el cuestionario validado Parental- Caregivers Perception Questionnaire (P-CPQ) como instrumento para la reunión de datos, aplicado en el entorno doméstico y contestado por el principal responsable. La relación entre los factores demográficos, el tipo de necesidad especial y el P-CPQ se evaluó con un alfa de 0,05. Resultados: los peores parámetros en la Escala de Impacto Familiar se observaron cuando la madre y el padre fueron los responsables de la transmisión de datos (p= 0,004). La salud oral se asoció con los peores parámetros de los síntomas orales sobre la calidad de vida a juicio de los padres (p = 0,012). No hubo diferencias estadísticamente significativas en cuanto al impacto del tipo de especialidad del niño en la calidad de vida. Conclusión: las variables "cuidador" y "estado de salud bucal del niño" se relacionan con los peores indicadores relativos al impacto de la salud bucal en la calidad de vida.

Resumo Introdução e objetivo: a OMS definiu o conceito de qualidade de vida como a autopercepção que o indivíduo tem sobre sua posição no contexto social, cultural e ideológico, sendo esses fatores os principais responsáveis por denotar os piores parâmetros quanto aos cuidados com a saúde bucal durante o exame clínico odontológico realizada pelo dentista. Avaliar o impacto da saúde bucal na qualidade de vida de crianças com necessidades especiais de cuidados de saúde de 7 a 14 anos de idade e a influência de diferentes tipos de especialidades na qualidade de vida, na visão dos pais/cuidadores na região sudeste do Brasil. Materiais e métodos: a amostra foi composta por 62 crianças matriculadas nas escolas públicas municipais e na Associação de Pais e Amigos dos Excepcionais. Foi utilizado o Parental- Caregivers Perception Questionnaire (P-CPQ) como um instrumento de mensuração, aplicado no ambiente familiar e respondido pelo responsável principal. A relação entre fatores demográficos, tipo de necessidade especial e o P-CPQ foi avaliada com alfa de 0,05. Resultados: os piores parâmetros em relação à qualidade de vida foram observados quando a mãe foi a responsável pela transmissão dos dados (p= 0,004). A variável estado de saúde bucal (p= 0,012) apresentou resultados relevantes quando relacionadas com os piores parâmetros na percepção do impacto da saúde bucal na qualidade de vida na percepção dos cuidadores sobre suas crianças. Não houve diferença estatisticamente significante com relação ao impacto do tipo de especialidade da criança na qualidade de vida. Conclusão: as variáveis cuidador e estado de saúde oral da criança estão relacionadas com os piores indicadores relativos ao impacto da saúde oral sobre a qualidade de vida.

Mood Disturbances, Anxiety, and Impact on Quality of Life in Patients Admitted to Epilepsy Monitoring Units.

Introduction: The overall combined prevalence of anxiety and depression in patients with epilepsy has been estimated at 20.2 and 22.9%, respectively, and is considered more severe in drug-refractory epilepsy. Patients admitted to epilepsy monitoring units constitute a particular group. Also, patients with psychogenic non-epileptic seizures can reach more than 20% of all admissions. This study aims to characterize these symptoms in a large cohort of patients admitted for evaluation in a tertiary epilepsy center. Materials and Methods: The study was conducted among 493 consecutive patients (age: 38.78 ± 12.7, 57% females) admitted for long-term video EEG from January 2013 to February 2021. Demographic, clinical, and mood disorder patients' data were collected. Anxiety and depression symptoms were assessed through the Hospital Anxiety Depression Scale (HADS-A and HADS-D), the State Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI-II). Quality of life was determined using the QOLIE-10. Patients were divided into three groups: patients with epilepsy (n = 395), psychogenic non-epileptic seizures (PNES) (n = 56), and combined (n = 33). A univariate and multivariate regression analysis was performed for variables associated with quality of life. Results: Of 493 patients, 45.0% had structural etiology, and considering epilepsy classification, 43.6% were of temporal lobe origin. In addition, 32.45% of patients had a previous psychiatric history, 49.9% of patients had depressive symptoms in BDI, and 30.9% according to HADS-D; 56.42 and 52.63% of patients presented pathological anxiety scores in STAI-T and STAI-S, respectively; and 44.78% according to HADS-A. PNES and combined groups revealed a higher incidence of pathologic BDI scores (64.29 and 78.79%, p < 0.001) as well as pathologic HADS-A scores (p = 0.001). Anxiety and depression pathologic results are more prevalent in females, HADS-A (females = 50.7%, males = 36.8%; p = 0.0027) and BDI > 13 (females = 56.6%, males = 41.0%; p = 0.0006). QOLIE-10 showed that 71% of the patients had their quality of life affected with significantly higher scores in the combined group than in the epilepsy and PNES groups (p = 0.0015). Conclusions: Subjective anxiety, depression, and reduced quality of life are highly prevalent in patients with refractory epilepsy. These symptoms are more evident when PNES are associated with epilepsy and more severe among female patients. Most of the cases were not previously diagnosed. These factors should be considered in everyday clinical practice, and specific approaches might be adapted depending on the patient's profile.

Antisaccades and memory-guided saccades in genetic generalized epilepsy and temporal lobe epilepsy.

OBJECTIVE: Oculomotor tasks can be used to measure volitional control of behavior sensitive to frontal dysfunction. This study aimed to examine the saccadic eye movement in Genetic Generalized Epilepsy (GGE) which could correlate with the abnormality of the frontal lobe or the thalamo-frontal network. METHODS: Twenty-one patients with GGE were compared with 22 patients with Temporal Lobe Epilepsy (TLE) and 39 healthy controls. Visual-guided saccades, Antisaccades, and Memory-guided saccades as oculomotor tasks were performed using a novel gaze-tracker designed for clinical practice use. RESULTS: Patients with epilepsy (either GEE or TLE) had similar latency, accuracy, and velocity in visual-guided saccades and memory-guided saccades. Patients with epilepsy had similar latencies and correct antisaccade number. However, healthy volunteers, matched by age, had faster responses and more accurate results than patients with epilepsy. CONCLUSIONS: Our investigations did not reveal differences between TLE and GGE patients' groups in visually guided saccades, antisaccades, and memory-guided saccades, thus suggesting that the frontal cortical mechanisms responsible for them are not explicitly impaired in patients with GGE.

Gender inequalities in the dental science: An analysis of high impact publications.

OBJECTIVE: To assess the participation of women in publications of dental journals with a high impact factor. METHODS: Articles published in 2016, 2011, and 2006 in 10 dental journals chosen for their highest impact factors in each dental fields were included in this research. Articles-related variables collected included the country of origin of each author, the type of study, and gender of the researchers. Gender was examined through PubMed, Scopus, ResearchGate, and respective affiliated institutions. Furthermore, a website designed to discover the gender of names was used when the previous alternatives were not conclusive. Forward stepwise Poisson regression models were used for data analysis. RESULTS: A total of 3365 studies were included in the first authorship analysis and 3398 in analysis related to last authorship. The prevalence of women as first authors was 37.2% (confidence interval (CI) 95% 34.5-37.5) and as last authors was 22.6% (CI 95% 21.3-23.9). Having a woman as the last author increased the presence of women in the first author position in scientific dental articles by 16% (prevalence ratio = 1.16, CI 95% [1.04-1.29]). The year of publication, journal, and region of the author were associated with an increase in the prevalence of women as last authors. From 2006 to 2016, the prevalence of women as last authors increased by 61%. Despite these trends, women were still underrepresented in science in the evaluated period. CONCLUSIONS: There are meaningful gender inequalities in publications of scientific dental papers. Encouraging women to lead research groups can reduce the inequities observed in the present study.

Periodontal disease and preterm birth: Findings from the 2015 Pelotas birth cohort study.

OBJECTIVES: To verify the association between periodontal conditions and preterm birth. MATERIALS AND METHODS: This study used data from the 2015 Pelotas Birth Cohort Study, Brazil. Pregnant women expected to give birth in 2015 were interviewed and dentally examined by a trained dentist, with periodontal measures collected in all teeth, six sites per tooth. Exposure was periodontal disease. Outcomes were preterm birth (all births <37 weeks of gestational age) and early preterm birth (<34 weeks). Analysis was carried out using Poisson regression according to a directed acyclic graph. RESULTS: A total of 2,474 women participated in the study. Incidence of preterm births was 10.2% and of early preterm births was 3.5%. Frequency of gingivitis was 21.7%, and periodontitis was 14.9%. Periodontitis was associated with a risk almost two times higher of having early preterm delivery compared with healthy pregnant women (RR 1.93; 95% CI 1.09-3.43). Presence of 5+ mm periodontal pocket with bleeding on probing was also associated with higher risk for early preterm delivery. CONCLUSIONS: The association between periodontal disease in pregnancy and the occurrence of preterm delivery is sensitive to the case definitions. Periodontal disease increased the risk of early preterm delivery.

Haemoproteus syrnii (Haemosporida: Haemoproteidae) in owls from Brazil: morphological and molecular characterization, potential cryptic species, and exo-erythrocytic stages.

Haemoproteus syrnii is a haemosporidian parasite found in owls. Although morphological and molecular data on the species is available, its exo-erythrocytic development was never researched. In this study, we provide the morphological, morphometric, and molecular characterization of H. syrnii populations found in owl species from Minas Gerais, southeast Brazil. We also characterized the coalescent species delimitation based on the molecular and histopathology data. Samples from 54 owls from six different species were analyzed, generating 11 sequences of the cyt b gene, from which six were new sequences. The overall prevalence of infection was high (72.22%). The H. syrnii sequences were grouped into two well-supported independent clades, which included other Haemoproteus (Parahaemoproteus) species. This was supported by both the coalescent species delimitation analysis and by the genetic divergence between lineages of these distinct clades. There were small morphological and morphometric differences within the population presented in this study. However, when compared with other studies, the molecular analysis demonstrated considerable intraspecific variation and suggests potential cryptic species. The histopathological analysis revealed, for the first time, that lungs and skeletal muscle are exo-erythrocytic stage location of H. syrnii, and that the parasite is linked to the histopathological changes found in owls. This study brings new data from Haemoproteus species biology and host infection, and improves host-parasite relationship understanding under an owl conservation perspective.

Persistent asymptomatic or mild symptomatic hyperCKemia due to mutations in ANO5: the mildest end of the anoctaminopathies spectrum.

BACKGROUND: The ANO5 gene encodes for anoctamin-5, a chloride channel involved in muscle cell membrane repair. Recessive mutations in ANO5 are associated with muscular diseases termed anoctaminopathies, which are characterized by proximal or distal weakness, or isolated hyperCKemia. We present the largest series of patients with asymptomatic/paucisymptomatic anoctaminopathy reported so far, highlighting their clinical and radiological characteristics. METHODS: Twenty subjects were recruited retrospectively from the Neuromuscular Disorders Units database of two national reference centers. All had a confirmed genetic diagnosis (mean age of diagnosis was 48 years) established between 2015 and 2019. Clinical and complementary data were evaluated through clinical records. RESULTS: None of the patients complained about weakness or showed abnormal muscular balance. Among paucisymptomatic patients, the main complaints or findings were generalized myalgia, exercise intolerance and calf hypertrophy, occasionally associated with calf pain. All patients showed persistent hyperCKemia, ranging from mild-moderate to severe. Muscle biopsy revealed inflammatory changes in three cases. Muscle magnetic resonance imaging revealed typical signs (preferential involvement of adductor and gastrocnemius muscles) in all but one patient. In two cases, abnormal findings were detectable only in STIR sequences (not in T1). Three patients showed radiological progression despite remaining asymptomatic. Twelve different mutations in ANO5 were detected, of which seven are novel. CONCLUSIONS: Recessive mutations in ANO5 are a frequent cause of undiagnosed asymptomatic/paucisymptomatic hyperCKemia. Patients with an apparent indolent phenotype may show muscle involvement in complementary tests (muscle biopsy and imaging), which may progress over time. Awareness of anoctaminopathy as the cause of nonspecific muscular complaints or of isolated hyperCKemia is essential to correctly diagnose affected patients.

Collagen VI-related limb-girdle syndrome caused by frequent mutation in COL6A3 gene with conflicting reports of pathogenicity.

Recently the scientific community has started to view Bethlem myopathy 1 and Ullrich congenital muscular dystrophy as two extremes of a collagen VI-related myopathy spectrum rather than two separate entities, as both are caused by mutations in one of the collagen VI genes. Here we report three individuals in two families who are homozygous for a COL6A3 mutation (c.7447A> G; p.Lys2483Glu), and compare their clinical features with seven previously published cases. Individuals carrying homozygous or compound heterozygous c.7447A> G, (p.Lys2483Glu) mutation exhibit mild phenotype without loss of ambulation, similar to the cases described previously as Collagen VI-related limb-girdle syndrome. The phenotype could arise due to an aberrant assembly of Von Willebrand factor A domains. Based on these data, we propose that c.7447A> G, (p.Lys2483Glu) is a common pathogenic mutation.

A novel mutation in the mitochondrial MT-ND5 gene in a family with MELAS. The relevance of genetic analysis on targeted tissues.

We report the case of two members of the same family with a novel mitochondrial DNA (mtDNA) gene variant in the MT-ND5 gene associated with MELAS syndrome and discuss limitations of genetics studies. The m.13045A > G mutation was detected at very low load in the daughter's urine cells (5%) and at different levels in the skeletal muscle of both mother (50%) and daughter (84%), being absent in blood, hair and saliva. Our findings suggest that non-invasive genetic assessment in urine cells may not be a sensitive diagnostic method neither a good predictor of disease development in relatives of some families with mtDNA-associated MELAS, particularly if involving MT-ND5 gene.

Adesão ao tratamento para Tuberculose Multidroga Resistente (TBMDR): estudo de caso em ambulatório de referência, Niterói (RJ), Brasil / Adherence to Multidrug-Resistant Tuberculosis (MDR-TB) Treatment: case study in a reference outpatient clinic, Niterói (RJ), Brazil

Resumo Introdução Adesão ao tratamento e aumento das taxas de cura resultam da interação de fatores relacionados aos serviços de saúde, pacientes, sociedade e gestão pública. Objetivo Conhecer os fatores relativos à adesão ao tratamento da tuberculose multidroga resistente (TBMDR), na perspectiva dos usuários, profissionais e gestores. Método Estudo de caso de abordagem qualiquantitativa, diferentes fontes de evidência, estatística descritiva e análise de conteúdo das categorias: adesão, acesso, acolhimento, vínculo e responsabilização. Resultados Oferta gratuita da medicação, realização de exames no ambulatório, flexibilidade na agenda, busca de faltosos e vínculo com a equipe de saúde foram descritos como favoráveis à adesão; sendo a dificuldade de acesso aos benefícios sociais e equipe de saúde incompleta como desfavoráveis. Conhecimento sobre a doença atual, o tratamento e o desejo de cura foram relatados como importantes fatores para superar barreiras encontradas para adesão. Conclusão Apesar da existência de fatores desfavoráveis à adesão, as ações de acolhimento, vínculo e responsabilização desenvolvidas pelo serviço foram suficientes para promover a adesão neste grupo. Recomenda-se a melhoria do acesso aos benefícios assistenciais, implementação de novas formas de comunicação e articulação com outros segmentos públicos e da sociedade para o enfrentamento da TBMDR.

Abstract Background Adherence to treatment and high cure rates result from the interaction health services, patients, society and public management. Objective To determine the factors associated with adherence to multidrug-resistant tuberculosis (MDR-TB) treatment from the perspective of patients, professionals and managers. Method Case study using quali-quantitative approach, different sources of evidence, descriptive statistics and content analysis based on the categories: adherence, access, embracement, bonding and accountability. Results The free supply of medicines and exams in the clinic, flexibility of scheduling, active search for no-show patients and relationship with the health team were described as important factors for adherence. Difficult access to social benefits and absence of some professionals of health team were unfavorable factors for adherence. Knowledge of the current illness and its treatment associated with the patient's will were important aspects to overcome the barriers when conducting treatment. Conclusion Despite the existence of unfavorable factors, the actions of embracement, bonding and accountability were sufficient to promote adherence in this group. It is recommended to further promote access to welfare benefits, new forms of communication and collaboration with other public sectors and society to confront the MDR-TB.

Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.

BACKGROUND: Bethlem myopathy represents the milder phenotype of collagen type VI-related myopathies. However, clinical manifestations are highly variable among patients and no phenotype-genotype correlation has been described. We aim to analyse the clinical, pathological and genetic features of a series of patients with Bethlem myopathy, and we describe seven new mutations. METHODS: A series of 16 patients with the diagnosis of Bethlem myopathy were analyzed retrospectively from their medical records for clinical, creatine kinase (CK), muscle biopsy, and muscle magnetic resonance (MRI) data. Genetic testing was performed through next-generation sequencing of custom amplicon-based targeted genes panel of myopathies. Mutations were confirmed by Sanger sequencing. RESULTS: The most frequent phenotype consisted of proximal limb weakness associated with interphalangeal and wrists contractures. However, cases with isolated contractures or isolated myopathy were found. CK levels did not correlate with severity of the disease. The most frequent mutation was the COL6A3 variant c.7447A>G, p.Lys2486Glu, with either an homozygous or compound heterozygous presentation. Five new mutations were found in COL6A1 gene and other two in COL6A3 gene, all of them with a dominant heritability pattern. From these, a new COL6A1 mutation (c.1657G>A, p.Glu553Arg) was related to an oligosymptomatic phenotype with predominating contractures in the absence of weakness and a normal muscle MRI. Finally, the most common COL6A1 mutation reported to date that leads to an Ullrich phenotype (c. 868G>A, p.Gly290Arg), has been found here as Bethlem presentation. CONCLUSIONS: Manifestations of Bethlem myopathy are quite variable, so either contractures or weakness may be lacking, and no phenotype-genotype associations can be brought.

Polymorphism evidence in Plasmodium (Haemamoeba) lutzi Lucena, 1939 (Apicomplexa, Haemosporida) isolated from Brazilian wild birds.

Plasmodium parasites can infect great variety of bird species around the world inflicting the so called avian malaria, an illness that could be fatal in some cases and consequently, should be monitored and widely included into conservation programs. The aim of this study was to characterize two lineages of Plasmodium (Haemamoeba) lutzi found in some birds in the Atlantic Forest of Minas Gerais - Brazil, that were morphologically identified after blood smears analyses under light microscopy and molecularly by sequencing the mitochondrial cytochrome b gene (cyt b). Besides these two lineages could be clearly morphologically identified as P.(H.) lutzi, some variations in comparison with its original description were noticed: absence of meronts and gametocytes (early and fully grown) in polychromatic erythrocytes, the larger size of pigment granules in meronts and gametocytes, and the presence of small vacuoles between pigment accumulation in fully grow macrogametocytes. Moreover, a certain degree of genetic intraspecific diversity was also observed across the lineages of P. (H.) lutzi, indicating the existence of polymorphisms within this taxon, which is uncommon in Haemosporida. These results allow discussion about species boundaries within avian hemosporidians and highlight the importance of multidisciplinary approaches for a more efficient species identification and characterization.