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Objetivo: analisar o papel da tomografia computadorizada de tórax na avaliação do acometimento populacional por pneumonia durante a pandemia de COVID-19, em 2020. Método: Trata-se de um estudo retrospectivo onde foram analisados os laudos e imagens de 103 pacientes, internados no período de 01 a 30 de abril de 2020, com suspeita de pneumonia por COVID-19, Fortaleza, Ceará. Resultado: O quantitativo de pacientes que apresentaram imagens sugestivas para COVID-19 foi de 65% dos pacientes admitidos. A média geral de idade dos pacientes com tomografia positiva para infecção foi de 58,68 anos. Os principais achados descritos em laudos analisados foram: padrão de vidro fosco em 97,01 % dos casos, consolidações parenquimatosas em 13,43%, estrias em 29,85% e derrame pleural em 4,47% dos pacientes examinados. Conclusão: A tomografia computadorizada de tórax demonstra protagonismo como ferramenta diagnóstica e tem sido determinante para o isolamento e monitoramento de grande parcela dos pacientes infectados.

This study determined phytochemical composition, antifungal activity and toxicity in vitro and in vivo of Syzygium cumini leaves extract (Sc). Thus, was characterized by gas chromatography coupled to mass spectrometry and submitted to determination of Minimum Inhibitory (MIC) and Fungicidal concentrations (MFC) on reference and clinical strains of Candida spp. and by growth kinetics assays. Toxicity was verified using in vitro assays of hemolysis, osmotic fragility, oxidant and antioxidant activity in human erythrocytes and by in vivo acute systemic toxicity in Galleria mellonella larvae. Fourteen different compounds were identified in Sc, which showed antifungal activity (MIC between 31.25-125 μg/mL) with fungistatic effect on Candida. At antifungal concentrations, it demonstrated low cytotoxicity, antioxidant activity and neglible in vivo toxicity. Thus, Sc demonstrated a promising antifungal potential, with low toxicity, indicating that this extract can be a safe and effective alternative antifungal agent.

Atopic dermatitis is a chronic inflammatory dermatoses, pruritic and relapsing, with variable density in which attacks mostly patients in pediatric age group. Therefore, the disease can cause a series of psychological and social damage because of its consequences at the family’s routine. Thus, the disease gets involved at the daily activities and interpersonal relationship. In summary, this study objective is to review articles about atopic dermatitis’ impact on the life quality of pediatric patients and their caregivers, using integrative review and literature's descriptive as a method, with a quality approach, at SciELO and Google Scholar data base in the month of June of 2021 with the words: “atopic eczema”, “children”, “relatives” and “welfare”. It was found 200 articles written in English, Portuguese and Spanish, published between 2012 and 2021 that had public access. From this number, 11 studies were selected to compose this review’s data base. In conclusion, the atopic dermatitis negatively affects the daily life of pediatric patients and their caregivers. The discomfort caused by the pruritic eczema adds to sleep deprivation and affects the children’s development at school, family and psychosocial life. The worst of this disease is related to bad quality of life index. A better understanding of atopic dermatitis’ impact can positively affect the patient’s frequent treatment and therapeutic strategies.

Purpose: This study aimed to analyze the effect of a Pilates protocol on respiratory muscle strength and heart rate variability (HRV) in patients with type 2 diabetes. Method: A randomized clinical trial (RBR-2gc2qj) was conducted on a type 2 diabetic target population. Patients practiced the Pilates protocol for 8 weeks, with two visits per week. The variables tested were maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and HRV (time and frequency domains). All variables were tested for normal distribution. Using SPSS 21.0, analysis of variance was performed for variables with normal distribution, and the Wilcoxon and Friedman tests were used for variables that did not show a normal distribution, with a 5% significance level. Results: Forty-four participants were included in the study (intervention group: 22; control group: 22; mean age: 61.23 ± 8.49 years), most of whom were female (77.3%), married or in a consensual union (59.1%), had complete literacy (31.8%), and had an average body mass index of 26.96 ± 4.35 kg/m2. There were no significant differences in MIP and MEP before and after the protocol between the intervention and control groups. Regarding HRV, there were significant differences in autonomic modulation, especially between the moments before and during exercise and between the moments during and after exercise; however, it was not possible to determine which system (sympathetic or parasympathetic) is most involved in these changes. Conclusion: The exercise protocol based on the Pilates method did not alter respiratory muscle strength but promoted changes in HRV, especially between the moments before and during exercise and during and after exercise. Clinical Trial Registration Number: RBR-2gc2qj.

Background: Food is already recognized as a trigger for migraine, but its mechanism of action has not been fully clarified. There is evidence that they act on the pathogenesis of migraine, interfer...

INTRODUCTION: Temporomandibular disorder (TMD) is currently considered a central sensitization syndrome that belongs to the orofacial nociplastic pain group and offers great challenges for clinical practice. It can also be identified in individuals with sickle cell disease. Neuromodulation is a promising therapy that can help individuals with refractory chronic pain. To our knowledge, there is no treatment proposal for these individuals with chronic orofacial pain resulting from sickle cell disease. OBJECTIVE: This is a protocol of a randomized, double-blind, cross-over clinical trial. The purpose of this protocol is to investigate whether the immediate effect of transcranial direct current stimulation can be increased by adding the effect of peripheral sensory electrical stimulation. METHODS: Twenty women between 18 and 49 years of age will be screened to participate in this cross-over study where they will all receive the three types of protocol with a one-week washout. Active transcranial Direct Current Stimulation (tDCS) + active Peripheral Electrical Stimulation (PES); Active tDCS + PES sham and tDCS sham + PES sham. Stimulation with tDCS will be at 2 mA anodic over the motor cortex for 20 minutes ipsilateral to the most painful temporomandibular joint (TMJ). Peripheral electrical stimulation will be at 100 Hz over the most painful TMJ masseter muscle for 30 min. OUTCOME: The main outcome will be pain intensity assessed by VAS scale and by a pressure algometer in grams. In addition, endogenous pain modulation will be analyzed through the temporal summation of pain with Aesthesio precision tactile sensory filaments and conditioned pain modulation (CPM) evaluated by an algometer and thermal conditioned stimulus, as secondary outcomes. Data will be analyzed using ANOVA of repeated measures, controlling for confounding variables.

Resistant hypertension (RH) is characterized by the use of three or more antihypertensive drugs without reaching the goal of controlling blood pressure (BP). For a definitive diagnosis of RH, it is necessary to exclude causes of pseudoresistance, including the white-coat effect, errors in BP measurement, secondary hypertension, therapeutic inertia, and poor adherence to lifestyle changes and pharmacological treatment. Herein, we report the history of a patient with long-standing uncontrolled BP, even when using seven antihypertensive drugs. Causes of secondary hypertension that justified the high BP levels were investigated, in addition to the other causes of pseudo-RH. In view of the difficult-to-control BP situation, it was decided to hospitalize the patient for better investigation. After 5 days, he had BP control with practically the same medications previously used. Finally, all factors related to the presence of pseudo-RH are discussed, especially poor adherence to treatment. Poor adherence to antihypertensive treatment is common in daily medical practice, and its investigation is of fundamental importance for better management of BP.

Introdução: As doenças são responsável por maior parte das hospitalizações e mortes no mundo. Porém, a maioria delas podem ser previnas por ações realizadas na Atenção Básica. Objetivo: comparar a morbidade e mortalidade por Doenças Crônicas Não Transmissíveis, Hipertensão Arterial e Diabetes Mellitus nos anos 2012-2014 com a cobertura da Atenção Básica na região Nordeste do Brasil. Metodologia: Trata-se de estudo ecológico, retrospectivo, realizado no nordeste brasileiro com dados dos anos de 2012 e 2014 com dados disponíveis no Departamento de Informática do Sistema Único de Saúde. Foi realizada uma análise descritiva e analítica e correlacionada as taxas de internação e óbitos dos agravos estudados com cobertura da Atenção Básica. Resultados: Ao comparar a ocorrência de internação e óbito entre os anos de 2012 e 2014 observou-se redução no nordeste. Todavia, quando correlacionado com a cobertura da Atenção Básica, quanto maior a cobertura maior foi a ocorrência dos agravos. Conclusões: O estudo revelou a necessidade de reflexão e tomada de atitude pelos gestores e profissionais de saúde considerando a continuidade do cuidado ao usuário da Atenção Básica, bem como todos os investimentos financeiros realizados pelo Ministério da Saúde junto aos municípios do Nordeste do Brasil.

Background: Hemispherotomy is the treatment of choice for children with refractory epilepsy. Although hemiplegia, sensory and motor impairments result from this surgical procedure, seizure control is effective as well as anticonvulsant dose reduction. Description of functional gains after rehabilitation of these children are still incomplete. Aims: To evaluate the effects of an early intensive rehabilitation program in the gross motor function of lower limbs after 30, 90, 180 and 360 days of surgery for the treatment of epilepsy (hemispherotomy), and compare to historic controls. Materials and Methods: prospective and longitudinal case series, with historic controls. Fourteen out of sixteen children who underwent hemispherotomy from January 2012 to February 2013 received an early rehabilitation protocol (ERP). Functional assessment included the Berg Balance Scale (BBS), Fugl-Meyer Scale (FMS) lower limb subscale, and Gross Motor Function System of Classification (GMFCS), as well as the need of wheelchairs and walking aids. A historical group of 13 children who received a conventional rehabilitation protocol (CRP) was used as control. Results: FMS and BBS improved in ERP subjects until 6 months after surgery and reached a plateau. One year after hemispherotomy, all children in the ERP group could walk independently and had mild limitations to mobility whereas, among those in the CRP subjects, there was a higher prevalence of musculoskeletal deformities and severe gait restrictions. Conclusions: ERP promotes rapid functional recovery during one-year follow-up and, as compared to the CRP group, the average functional capacity of the ERP group was considerably higher. These data support the beneficial effects of a specific, individualized and early rehabilitation approach for such patients.

Viruses are associated with several human diseases that infect a large number of individuals, hence directly affecting global health and economy. Owing to the lack of efficient vaccines, antiviral therapy and emerging resistance strains, many viruses are considered as a potential threat to public health. Therefore, researches have been developed to identify new drug candidates for future treatments. Among them, antiviral research based on natural molecules is a promising approach. Phospholipases A2 (PLA2s) isolated from snake venom have shown significant antiviral activity against some viruses such as Dengue virus, Human Immunodeficiency virus, Hepatitis C virus and Yellow fever virus, and have emerged as an attractive alternative strategy for the development of novel antiviral therapy. Thus, this review provides an overview of remarkable findings involving PLA2s from snake venom that possess antiviral activity, and discusses the mechanisms of action mediated by PLA2s against different stages of virus replication cycle. Additionally, molecular docking simulations were performed by interacting between phospholipids from Dengue virus envelope and PLA2s from Bothrops asper snake venom. Studies on snake venom PLA2s highlight the potential use of these proteins for the development of broad-spectrum antiviral drugs.

The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist. Copy number variants (CNVs) in the 22q11.2 region were investigated by multiplex ligation-dependent probe amplification (MLPA) for all individuals. The CMA was performed only for individuals with additional major features. MLPA revealed pathogenic CNVs at the 22q11 region in 3/54 (5.6%) individuals. CMA revealed pathogenic CNVs in 4/17 (23.5%) individuals, including the three CNVs at the 22q11 region also detected by MLPA, and CNVs classified as variants of unknown significance (VOUS) in 4/17 (23.5%) individuals. Pathogenic alterations were found at the 2p12, 5p15, 13q13, and 22q11 regions. VOUS were found at 3q29, 5q22.2, 5q22.1, and 9p22 regions. All individuals with pathogenic alterations presented additional major features, including congenital heart disease (CHD). The literature review revealed pathogenic CNVs in 17/193 (8.8%) individuals and most of them also presented additional major features, such as CHD, renal anomalies, or developmental delay. In conclusion, CNVs should be investigated in patients with CFM and additional major features.

INTRODUÇÃO: A atividade física feita de maneira regular tem grande eficácia no retardo do declínio fisiológico do processo do envelhecimento, mantém e otimiza a capacidade física, melhora a funcionalidade e tem expressão no propósito de vida na velhice. OBJETIVO: caracterizar e descrever as condições sociodemográficas, físicas e de propósito de vida em um grupo de idosos praticantes de atividade física regular no interior do Amazonas. MÉTODOS: Estudo transversal com idosos ativos da comunidade que realizam atividade física em suas comunidades por pelo menos 3 vezes na semana em torno de 50 minutos. Estes foram avaliados através de questionários e escalas validadas: Mini Exame Exame Estado Mental (MEEM), Teste de Trilha, Propósito de Vida, Teste Short PhysicalPerformanc e Battery (SPPB), Índice de Comorbidades Funcional, Escala numérica de dor e foram coletados dados referentes às características sociodemográficas. RESULTADOS: Dos 36participantes,100% são naturais do interior do Amazonas; 28 (77%) sobrevivem com renda mensal de salário mínimo; 27(75%) relatam sentir dor em alguma parte do corpo e 21(58,3%) apresentaram sobrepeso ou obesidade grau 1,33(91,6%) diz se sentir bem quando pensam no passado e no futuro. CONCLUSÃO: apesar de sentir dor, de baixa renda e baixa escolaridade,os idosos praticam atividade física que traz benefícios como manutenção da saúde física, diminuição dos sintomas depressivos, percepção de realização, motivação, satisfação e felicidade em viver.

Juvenile ossifying fibroma is an uncommon, fast-growing benign neoplasm classified within the group of fibro-osseous lesions that directly affect the face and the jaws. Although it is not followed by metastasis, it usually presents a highly aggressive nature. It is histopathologically divided into two patterns: trabecular and psammomatoid. It can be differentiated through the age of the patients, anatomic location and behavior of the lesion. In this context, this paper reports on the findings of a rare pathology case: juvenile ossifying fibroma, focusing primarily on its clinical, medical imaging and histopathological features characteristics, in order to familiarize the dentist, provide correct diagnosis and the most appropriate treatment.

Introduction: Several drugs were withdrawn from the market due to safety. Objective: The aim of this study was to describe data supporting drug withdrawal from the market due to safety reasons in countries belonging to the World Health Organization. Methods: We analyzed drugs withdrawn from the market between 1990 and 2010. All medicine agencies of the countries belonging to the Program for International Drug Monitoring of the World Health Organization were contacted. To complete data, Medline, reference books and available drug databases were also searched. Information sources on which authorities based their withdrawal were categorized and the average time between the first date of exposure and withdrawal was calculated and stratified. Results: A total of 133 drugs that met the inclusion/exclusion criteria were withdrawn from the market due to safety reasons in the period reviewed (1990 - 2010). Hepatotoxicity (n=36, 27.1%), cardiac disorders (n=25, 18.8%), hypersensitivity (n=17, 12.8%) and nephrotoxicity (n=14, 9.8%) were the major reasons responsible for 69.2% of all drugs withdrawn. In most cases, Information Sources for drug withdrawal were spontaneous reports and/or case reports (n=86, 64.7%), followed by clinical trials (n=24, 18.0%). The average time between the introduction of a drug and its withdrawal due to safety reasons was 20.3 years (SD±13.8). Conclusion: According to available and published evidence, there is no gold standard to identify risks associated with drug exposure. These findings strengthen the role of different information sources within the drug safety review process.

The tuberous sclerosis complex (TSC), focal cortical dysplasia IIB (FCD IIB), and hemimegalencephaly (HME) exhibit similar molecular features that are dependent on the hyperactivation of the mTOR pathway. They are all associated with refractory epilepsy and the need for surgical resection with varying outcomes. The phosphorylated protein S6 (pS6) is a downstream target of mTOR, whose increased expression might indicate mTOR hyperactivation, but which is also present when there is no alteration in the pathway (such as in FCD type I). We have performed immunohistochemical marking and quantification of pS6 in resected brain specimens of 26 patients clinically and histologically diagnosed with TSC, FCD IIB, or HME and compared this data to a control group of 25 patients, to measure the extent of pS6 positivity and its correlation with clinical aspects. Our results suggest that pS6 may serve as a reliable biomarker in epilepsy and that a greater percentage of pS6 marking can relate to more severe forms of mTOR-dependent brain anomalies.

Individuals with sickle cell disease (SCD) exhibit changes in static brain connectivity in rest. However, little known as chronic pain associated with hip osteonecrosis affects dynamic brain connectivity during rest and the motor imagery task. The aim of this study was to investigate the characteristics of the dynamic functional brain connectivity of individuals with SCD and chronic pain secondary to hip osteonecrosis. This is a cross-sectional study comparing the dynamic brain connectivity of healthy individuals (n = 18) with the dynamic brain connectivity of individuals with SCD and chronic pain (n = 22). Individuals with SCD and chronic pain were stratified into high- or low-intensity pain groups based on pain intensity at the time of assessment. Dynamic brain connectivity was assessed through electroencephalography in 3 stages, resting state with eyes closed, and during hip (painful for the SCD individuals) and hand (control, nonpainful) motor imagery. Average weight of the edges and full synchronization time (FST)—time required for 95% of the possible edges to appear over time during a given task—were evaluated. Regarding the average weight of the edges, individuals with SCD and high-intensity pain presented higher edge weight during hip motor imagery. The average weight of the edges correlated positively with pain intensity and depression symptoms. Individuals with SCD and chronic pain complete the cerebral network at rest more quickly (lower FST). Individuals with SCD and chronic pain/hip osteonecrosis have impaired dynamic brain network with shorter FST in rest network and more pronounced diffuse connectivity in individuals with high-intensity pain. The dynamic brain network evaluated by time-varying graphs and motif synchronization was able to identify differences between groups.

Background Anaemia is a prevalent health problem worldwide. Some types are preventable or controllable with iron supplementation (pills or drops), fortification (sprinkles or powders containing iron added to food) or improvements to dietary diversity and quality (e.g. education or counselling). Objectives To summarise the evidence from systematic reviews regarding the benefits or harms of nutrition-specific interventions for preventing and controlling anaemia in anaemic or non-anaemic, apparently healthy populations throughout the life cycle. Methods In August 2020, we searched MEDLINE, Embase and 10 other databases for systematic reviews of randomised controlled trials (RCTs) in anaemic or non-anaemic, apparently healthy populations. We followed standard Cochrane methodology, extracting GRADE ratings where provided. The primary outcomes were haemoglobin (Hb) concentration, anaemia, and iron deficiency anaemia (IDA); secondary outcomes were iron deficiency (ID), severe anaemia and adverse effects (e.g. diarrhoea, vomiting). Main results We included 75 systematic reviews, 33 of which provided GRADE assessments; these varied between high and very low. Infants (6 to 23 months; 13 reviews) Iron supplementation increased Hb levels and reduced the risk of anaemia and IDA in two reviews. Iron fortification of milk or cereals, multiple-micronutrient powder (MMNP), home fortification of complementary foods, and supplementary feeding increased Hb levels and reduced the risk of anaemia in six reviews. In one review, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia. In another, caterpillar cereal increased Hb levels and IDA prevalence. Food-based strategies (red meat and fortified cow's milk, beef) showed no evidence of a difference (1 review). Preschool and school-aged children (2 to 10 years; 8 reviews) Daily or intermittent iron supplementation increased Hb levels and reduced the risk of anaemia and ID in two reviews. One review found no evidence of difference in Hb levels, but an increased risk of anaemia and ID for the intermittent regime. All suggested that zinc plus iron supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverage versus control, and point-of-use fortification of food with iron-containing micronutrient powder (MNP) versus placebo or no intervention may increase Hb levels and reduce the risk of anaemia and ID. Fortified dairy products and cereal food showed no evidence of a difference on the incidence of anaemia (1 review). Adolescent children (11 to 18 years; 4 reviews) Compared with no supplementation or placebo, five types of iron supplementation may increase Hb levels and reduce the risk of anaemia (3 reviews). One review on prevention found no evidence of a difference in anaemia incidence on iron supplementation with or without folic acid, but Hb levels increased. Another suggested that nutritional supplementation and counselling reduced IDA. One review comparing MMN fortification with no fortification observed no evidence of a difference in Hb levels. Non-pregnant women of reproductive age (19 to 49 years; 5 reviews) Two reviews suggested that iron therapy (oral, intravenous (IV), intramuscular (IM)) increased Hb levels; one showed that iron folic acid supplementation reduced anaemia incidence; and another that daily iron supplementation with or without folic acid or vitamin C increased Hb levels and reduced the risk of anaemia and ID. No review reported interventions related to fortification or dietary diversity and quality. Pregnant women of reproductive age (15 to 49 years; 23 reviews) One review apiece suggested that: daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at delivery and in the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery; intermittent iron supplementation had no effect on Hb levels and IDA, but increased the risk of anaemia at or near term and ID, and reduced the risk of side effects; vitamin A supplementation alone versus placebo, no intervention or other micronutrient might increase maternal Hb levels and reduce the risk of maternal anaemia; MMN with iron and folic acid versus placebo reduced the risk of anaemia; supplementation with oral bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side effects; MNP for point-of-use fortification of food versus iron and folic acid supplementation might decrease Hb levels at 32 weeks' gestation and increase the risk of anaemia; and LNS versus iron or folic acid and MMN increased the risk of anaemia. Mixed population (all ages; 22 reviews) Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people (4 reviews). Hb levels appeared to increase and risk of anaemia and ID decrease in two reviews investigating MMN fortification versus placebo or no treatment, iron fortified flour versus control, double fortified salt versus iodine only fortified salt, and rice fortification with iron alone or in combination with other micronutrients versus unfortified rice or no intervention. Each review suggested that fortified versus non-fortified condiments or noodles, fortified (sodium iron ethylenediaminetetraacetate; NaFeEDTA) versus non-fortified soy sauce, and double-fortified salt versus control salt may increase Hb concentration and reduce the risk of anaemia. One review indicated that Hb levels increased for children who were anaemic or had IDA and received iron supplementation, and decreased for those who received dietary interventions. Another assessed the effects of foods prepared in iron pots, and found higher Hb levels in children with low-risk malaria status in two trials, but no difference when comparing food prepared in non-cast iron pots in a high-risk malaria endemicity mixed population. There was no evidence of a difference for adverse effects. Anaemia and malaria prevalence were rarely reported. No review focused on women aged 50 to 65 years plus or men (19 to 65 years plus). Authors' conclusions Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children may have prophylactic benefits for malaria endemicity low-risk populations. In any age group, only a limited number of reviews assessed interventions to improve dietary diversity and quality. Future trials should assess the effects of these types of interventions, and consider the requirements of different populations.

Staphylococcus aureus is one of the main bacterial agents responsible for cases of mastitis in ruminants, playing an important role in the persistence and chronicity of diseases treated with antimicrobials. Using the multilocus sequence typing technique, network approaches and study of the population diversity of microorganisms, we performed analyzes of S. aureus (ES-GPM) isolated from goats with persistent mastitis (GPM). The most strains of ES-GPM were categorically different phylogenetically from the others and could be divided into two lineages: one with a majority belonging to ES-GPM and the other to varied strains. These two lineages were separated by 27 nuclear polymorphisms. The 43 strains comprised 22 clonal complexes (CCs), of which the ES-GPM strains were present in CC133, CC5 and a new complex formed by the sequence type 4966. The genetic diversity of some alleles showed be greater diversity and polymorphism than others, such as of the aroE and yqiL genes less than glpF gene. In addition, the sequences ES-GPM to the arc gene and glpF alleles showed the greatest number of mutations for ES-GPM in relation to non-ES-GPM. Therefore, this study identified genetic polymorphisms characteristic of S. aureus isolated from milk of goats diagnosed with persistent mastitis after the failed treatment with the antibiotic enrofloxacin. This study may help in the future to identify and discriminate this agent in cases of mastitis, and with that, the most appropriate antibiotic treatment can be performed in advance of the appearance of persistent mastitis caused by the agent, reducing the chances of premature culling and animal suffering.

Foot angioleiomyomas are rare tumors that are more prevalent in older women, may be asymptomatic, and rarely recur after surgical excision. We report an atypical case in a young woman of a painful and recurrent angioleiomyoma after excision. Level of Evidence V; Diagnostic Studies; Expert Opinion.

The aims were to examine changes in the prevalence of overweight and obesity among students from 2001 to 2011, and to verify if these changes differ according to age group, area of residence, and family income. We analyzed two cross-sectional surveys conducted in 2001 and 2011 with brazilian adolescents. Sociodemographic and anthropometric characteristics were self-reported using a questionnaire. Multinomial logistic regression was used to analyze changes in overweight and obesity between the two surveys. The nutritional status was the outcome of the present study and the surveys (2001 and 2011) were the exposure. The odds of being overweight and obese were higher among boys and girls in urban areas in the 2011 survey compared to the 2001. Boys and girls with higher income were also more likely to present overweight and obesity in the second survey compared to the first. An increase of overweight and obesity was observed over a decade. We suggest that future interventions consider the area of residence and the family income to strengthen the effectiveness of actions developed to prevent and control these indicators among adolescents.

Objective: To assess the quality of life and functional status of patients subjected to debridement of ulcers in the posterior ankle who required complete Achilles tendon resection without any type of reconstruction or tendon transfer. Method: This is a case series of 5 (mostly diabetic) patients who underwent complete Achilles tendon resection due to an ulcer in the posterior ankle region. Preservation of the Achilles tendon was prevented due to tendon exposure, extensive degeneration and the need for infection control. Patients answered the Brazilian Portuguese version of the Achilles Tendon Total Rupture Score (ATRS-BR) questionnaire and the 36-item Short-Form Health Survey (SF-36) during the postoperative period, and follow-up varied between 6 and 24 months. The ATRS-BR ranges from 0 to 100, and higher scores indicate fewer symptoms and limitations. The SF-36 consists of 36 questions comprising 8 domains, which are independently assessed and given a score of up to 100 points, with higher scores indicating better health status. Results: The mean age of patients was 70 years. The mean score on the SF-36 physical functioning domain was 70 (50-95) points. The mean value of the ATRS-BR was 54.6 (31-88) points; however, the patients had few complaints about their functional status. Conclusion: Non-reconstruction of the Achilles tendon in predominantly diabetic elderly patients with posterior ankle ulcers presents encouraging functional outcomes. This study suggests that complete Achilles tendon resection is a viable option for ulcer treatment in this population. Level of Evidence IV; Therapeutic Studies; Cases Series.

The aim of this study was to verify the effects of swimming-learning program of mental health parameters, cognition and motor coordination in students with Attention Deficit Hyperactivity Disorder (ADHD). Thirty-three children of both sexes between 11 and 14 years were randomized into trained group (n = 18) and untrained group (n = 15). The training was performed for 8 weeks. Then, before and after 48 h of training period of both groups were submitted to find the mental health, cognition, motor coordination test, and physical fitness. Our results demonstrate that the aquatic exercise program significantly improved the depression parameters (p = 0.048), stress (p = 0.039), cognitive flexibility (p = 0.042) and selective attention (p = 0.047). In relation to motor coordination and physical fitness, the results showed significant improvements in the coordination of lower limbs laterality (p = 0.05), flexibility (p = 0.049), and abdominal resistance (p = 0.037). Taken together, the results suggest that swimming-learning program significantly improved the mental health, cognition, and motor coordination in children with ADHD.

OBJECTIVEThe objective of this study was to describe a new experimental model of hemispherotomy performed on laboratory animals.METHODSTwenty-six male young adult Wistar rats were distributed into two groups (surgery and control). The nonfluorescent anterograde neurotracer biotinylated dextran amine (BDA; 10,000 MW) was microinjected into the motor cortex area (M1) according to The Rat Brain in Stereotaxic Coordinates atlas to identify pathways and fibers disconnected after the experimental hemispherectomy. SPECT tomographic images of 99mTc hexamethylpropyleneamine oxime were obtained to verify perfusion in functioning areas of the disconnected and intact brain. A reproducible and validated surgical procedure is described in detail, including exact measurements and anatomical relationships. An additional 30 rodents (n = 10 rats per group) were divided into naïve, sham, and hemispherotomy groups and underwent the rotarod test.RESULTSCortico-cortical neural pathways were identified crossing the midline and contacting neuronal perikarya in the contralateral brain hemisphere in controls, but not in animals undergoing hemispherotomy. There was an absence of perfusion in the left side of the brain of the animals undergoing hemispherotomy. Motor performance was significantly affected by brain injuries, increasing the number of attempts to maintain balance on the moving cylinder in the rotarod test at 10 and 30 days after the hemispherotomy, with a tendency to minimize the motor performance deficit over time.CONCLUSIONSThe present findings show that the technique reproduced neural disconnection with minimal resection of brain parenchyma in young adult rats, thereby duplicating the hemispherotomy procedures in human patients.

Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment. Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF. Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submitted to a ventricular-subcutaneous shunt (VSCS) 1 week after induction. All animals were euthanized at 21 days of age. They underwent motor function and memory testing as well as brain MRI scans. Histopathological analysis for glial fibrillary acidic protein and Ki-67 was done, and CSF was collected for measurement of IL-1β, IL-6, and TNF-α. Results: The average time to reach the water maze platform was highest in the untreated hydrocephalic group. The magnetization transfer rates were 37.21 and 33.76 before and after shunting, respectively. The mean astrocyte counts were 2.45, 1.36, and 90.5 for shunted, untreated, and control animals, respectively. The mean CSF IL-1β concentrations were 62.3 and 249.6 pg/mL, the average IL-6 levels were 104.2 and 364.7 pg/mL, and the average TNF-α values were 4.9 and 170.5 pg/mL for the treated hydrocephalic group and the untreated group, respectively. Conclusions: Pups treated with a CSF shunt showed better performance on memory tests. VSCS did not revert demyelination caused by hydrocephalus. Likewise, reactive astrocytosis and cell proliferation over the germinal matrix were not reversed after shunting. Hydrocephalic animals had raised levels of inflammatory interleukins, which returned to normal after treatment.

Cancer is a set of numerous diseases characterized by the abundant and disordered growth of cells. In the pediatric population, central nervous system tumors account for 20% of neoplasms. In this scenario, it is necessary to highlight that patients with tumors in the posterior fossa and aggressive treatments, such as exposure to cranial radiotherapy, have been associated with a decline in cognitive functioning. Thus, the main objective of this research was to evaluate, through theoretical and empirical studies of national and international literature, the cognitive impact on individuals with brain neoplasms in the posterior fossa region. To achieve this goal, the descriptors "brain neoplasms", "cognitive dysfunction" and "child development" were used in the LILACS-BVS, SciELO, and MEDLINE/PubMed databases, being considered as inclusion criteria articles published in the last five years (2016 -2020) and excluding articles whose methodology was inconsistent and bibliographic reviews; 4 articles were selected as a research sample. Based on the selected articles, it can be identified, in general, that the association between cognitive decline and infratentorial brain neoplasms is due to the form of treatment normally suggested to deal with this disease. Furthermore, a direct relationship was perceived between aggressive treatments – such as chemotherapy and radiotherapy – and long-term decline. However, few articles on the subject were identified, and it is possible to conclude that there is a gap in this segment, making it necessary to develop more research in the area.

Manoel Paz Landim, Luciana Neves Cosenso-Martin, Aleandra Polegati Santos, Jessica Rodrigues Roma Uyemura, Leticia Barufi Fernandes, Valquiria da Silva Lopes, Juan Carlos Yugar-Toledo, Jose Fernando Vilela-Martin Internal Medicine Department, State Medical School at Sao Jose do Rio Preto (FAMERP), Sao Jose do Rio Preto, Sao Paulo, BrazilCorrespondence: Jose Fernando Vilela-MartinInternal Medicine Department, State Medical School at Sao Jose do Rio Preto (FAMERP), Ave Brig Faria Lima 5416, Vila Sao Pedro, Sao Jose do Rio Preto, 15090-000, Sao Paulo, BrazilEmail vilelamartin@uol.com.brBackground: The causal relationship between systemic arterial hypertension and target organ damage (TOD) is well known, as well as the association with cardiovascular risk factors (CV). Ambulatory blood pressure monitoring (ABPM) is important in monitoring hypertension and assessing the risk of TOD.Objective: To evaluate the relationship between blood pressure (BP) and clinical and biochemical parameters in the development of TOD in hypertensive patients.Methods: This was a retrospective cohort study with 162 hypertensive patients followed for an average period of 13 years. The TOD investigated were left ventricular hypertrophy (LVH), microalbuminuria, coronary artery disease (CAD) and stroke. Blood pressure was assessed by ABPM and LVH using echocardiogram and electrocardiogram, respectively. Biochemical-metabolic tests and 24-hour microalbuminuria were performed at baseline and follow-up. The P-value < 0.05 was considered significant.Results: The average age was 69± 11.8 years, with a predominance of women (64.8%), white ethnicity (79.6%) and diabetics (78.4%). ABPM showed a significant reduction in BP values during follow-up, although without association with TOD (microalbuminuria, stroke, and CAD), except for LVH that showed a correlation with sleep BP ≥ 120/70 mmHg (P=0.044). The most frequent TODs were LVH (29.6%), microalbuminuria (26.5%), CAD (19.8%) and stroke (17.3%). In the follow-up, there was an association between LVH and diabetes; microalbuminuria was associated with diabetes and triglycerides; stroke was associated with HDL-cholesterol (HDL-c), microalbuminuria and carotid disease. CAD showed a relationship with age and HDL-c.Conclusion: Predictive factors for TOD are age, microalbuminuria, diabetes, HDL-c, triglycerides and carotid disease. Nocturnal BP is correlated with LVH. The absence of a relationship between ABPM and other TODs can be explained by the use of effective drugs, improvement of metabolic and blood pressure parameters.Keywords: arterial hypertension, ambulatory blood pressure monitoring, left ventricular hypertrophy, albuminuria, stroke, coronary artery disease

Objective: To associate the sociodemographic variables of elderly women with cervical cancer and staging of an oncology reference hospital. Method: An observational, retrospective analytical study of 559 elderly women. Results: The variables that presented a statistically significant correlation with cervical cancer staging were: married elderly women, histopathological squamous cell carcinoma, radiotherapy + chemotherapy as the first treatment received in the hospital, complete remission of the disease at the end of the first treatment, without deaths from cancer and never having smoked. Conclusion: Although some characteristics are related to higher prevalence, they were not associated with staging, such as older ages. Early treatment was also an aspect associated with less late staging. Thus, the study reaffirms the importance of knowing the epidemiological characteristics of these women, as it favors the planning an devaluation of effective programs in the control of cervical cancer. Keywords: Cancersofthecervix; Aging; Women'shealth.

Background Immune-related adverse events (IrAEs) associated with the use of immune checkpoint inhibitors (ICIs) may not be fully covered by existing measures like the PRO-CTCAE™. Selecting PRO-CTCAE™ items for monitoring symptomatic adverse events is hindered by the heterogeneity and complexity of IrAEs, and no standardised selection process exists. We aimed to reach expert consensus on the PRO-CTCAE™ symptom terms relevant for cancer patients receiving ICIs and to gather preliminary expert opinions about additional symptom terms reflecting ICI symptomatic toxicities. Additionally, we gathered expert consensus about a core set of priority symptom terms for prospective surveillance and monitoring. Design This Delphi study involved an international panel of experts (n = 6 physicians; n = 3 nurses, n = 1 psychiatrist and n = 1 patient advocates). Experts prioritised the relevance and importance of symptom terms to monitor in patients treated with ICIs. Results Experts reached a consensus on the relevance of all (n = 80) PRO-CTCAE™ Symptom Terms. Consensus on the importance of these symptom terms for prospective monitoring in patients receiving ICIs was reached for 81% (n = 65) of these terms. Additional symptoms terms (n = 56) were identified, with a consensus that 84% (47/56) of these additional symptom terms should also be considered when monitoring symptomatic IrAEs. Conclusion This study identified a prioritised list of symptom terms for prospective surveillance for symptomatic IrAEs in patients receiving ICI treatment. Our results indicate the need to strengthen the validity of PRO measures used to monitor patients receiving ICIs. While these results provided some support for the content validity of the PRO CTCAE™ and resulted in a preliminary set of salient symptomatic adverse events related to the use of ICIs, broader international agreement and patient involvement are needed to further validate our initial findings.

Introduction: Hypertension and kidney function are closely related. However, there are few studies on renal function during acute elevation of blood pressure (BP), denominated hypertensive crisis (HC). Objectives: To evaluate the relationship between renal function and inflammatory cytokines in HC, subdivided into hypertensive urgency (HUrg) and emergency (HEmerg). Methods: 74 normotensive subjects (NT), 74 controlled hypertensive (ContrHT), 50 patients with HUrg and 78 with HEmerg were studied. The glomerular filtration rate (eGFR) was estimated, and cytokine levels were measured. Statistical analysis was performed using the Kruskal-Wallis or Mann-Whitney test and Spearman's correlation, with significant differences p-value Results: The eGFR was significantly lower in HEmerg group compared to the NT, ContrHT and HUrg groups. All cytokines were significantly elevated in patients with HC compared to the control groups (NT and ContrHT). In addition, the cytokines interleukin (IL)-1β, IL-6 and IL-10 were higher in the HEmerg group compared to the HUrg groups. There was a negative correlation between eGFR and the cytokines (IL-6, IL-8, IL-10 and TNF-α) in the HEmerg group. Conclusions: Elevated inflammatory cytokines are associated with reduced eGFR in individuals with HEmerg, indicating an involvement of the inflammatory process in the pathogenesis of acute elevations of BP.

This study aims to discuss diagnostic criteria and severity assessment for craniofacial microsomia (CFM). A series of 61 patients with diverse CFM phenotypes had their clinical data collected by experienced dysmorphologists using a single protocol. Genetic abnormalities were searched through karyotype and chromosomal microarray analysis. Sex ratio, prenatal risk factors, and recurrence rate corroborated the literature. Despite the wide variability of clinical findings, ear disruption was universal. Eight patients were assigned as syndromic, four of whom had demonstrable genetic alterations. The majority of patients (67.2%) fulfilled four known diagnostic criteria, while 9.8% fulfilled one of them. Data strengthened disruptions of the ear and deafness as a semiotically valuable sign in CFM. Facial impairment should consider asymmetry as a mild expression of microsomia. Spinal and cardiac anomalies, microcephaly, and developmental delay were prevalent among extra craniofacial features and should be screened before planning treatment and follow up. The severity index was able to recognize the less and the most affected patients. However, it was not useful to support therapeutic decisions and prognosis in the clinical scenario due to syndromic and non-syndromic phenotypes overlapping. These issues make contemporary the debate on diagnostic methods and disease severity assessment for CFM. They also impact care and etiopathogenetic studies.

Made available in DSpace on 2022-05-01T07:58:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico Background and purpose: Severe diarrhoea, a common gastrointestinal manifestation of anticancer treatment with irinotecan, might involve single nucleotide polymorphisms (SNPs) of toll-like receptors (TLRs), described as critical bacterial sensors in the gut. Here, colorectal cancer patients carrying missense TLR4 A896G (rs4986790) or C1,196T (rs4986791) SNPs and Tlr4 knockout (Tlr4−/−) mice were given irinotecan to investigate the severity of the induced diarrhoea. Experimental approach: Forty-six patients treated with irinotecan-based regimens had diarrhoea severity analysed according to TLR4 genotypes. In the experimental setting, wild-type (WT) or Tlr4−/− mice were given irinotecan (45 or 75 mg·kg−1, i.p.) or saline (3 ml·kg−1). Diarrhoea severity was evaluated by measuring intestinal injury and inflammatory markers expression after animals were killed. Key results: All patients with TLR4 SNPs chemotherapy-treated presented diarrhoea, whereas gastrointestinal toxicity was observed in 50% of the wild homozygous individuals. Mice injected with irinotecan presented systemic bacterial translocation and increased TLR4 immunostaining in the intestine. In line with the clinical findings, Tlr4 gene deficiency enhanced irinotecan-related diarrhoea and TLR9 expression in mice. An increased myeloperoxidase activity and Il-18 expression along with IL-10 decreased production in Tlr4−/− mice also indicated an intensified intestinal damage and inflammatory response. Conclusion and implications: TLR4 deficiency upregulates TLR9 expression and enhances intestinal damage and the severity of late-onset diarrhoea during irinotecan-based treatment. Identifying patients genetically predisposed to chemotherapy-associated diarrhoea is a strategy toward precision medicine. Graduate Program in Pathology Department of Pathology and Forensic Medicine Faculty of Medicine Federal University of Ceará Laboratory of Molecular Biology and Genetics Haroldo Juaçaba Hospital Cancer Institute of Ceará (ICC) Graduate Program in Pharmaceutical Sciences Department of Pharmacy Faculty of Pharmacy Nursing and Dentistry Federal University of Ceará Laboratory of Inflammation and Cancer Pharmacology Drug Research and Development Center (NPDM) Department of Physiology and Pharmacology Federal University of Ceará Cancer Cytogenomic Laboratory Drug Research and Development Center (NPDM) Federal University of Ceará Clinical Oncology Service Haroldo Juaçaba Hospital Cancer Institute of Ceará (ICC) Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP) Clinical Oncology Service Walter Cantídio University Hospital Federal University of Ceará Department of Pharmacology School of Medicine of Ribeirão Preto University of São Paulo Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP) CNPq: 310568/2017-0 CNPq: 421202/2018-1 CAPES: CAPES-PROEX 0756/2020 Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico: PR2-0101-00054.01.00/15

Demonstrate that transcranial ultrasonography (TUS) scanning is viable and useful as a diagnostic method in experimental hydrocephalus, as well as to compare measurements of cerebral and ventricular width obtained from TUS scans of hydrocephalic rats with post-mortem anatomical specimens, aiming for the development of accurate criteria to establish ventricular enlargement and progression of hydrocephalus subsequently. Thirty-five male Wistar rats were used. Following hydrocephalus induction, they underwent a transcranial ultrasound scan to measure cerebral and ventricular dimensions, in the fourth and 21 post-induction days. By the end of the experiments, measurements obtained from TUS scans were compared with actual values as seen in the post-mortem specimens of each animal. Ventricular dilation could be clearly visualized in hydrocephalic animals. We performed intraclass correlation coefficient and linear regression analyses that have demonstrated a precise correlation between measurements of TUS scans and post-mortem specimens; we have found a similarity of 0,95 for the cerebral diameter and 0,97 for ventricular width. Transcranial ultrasonography is a useful and reliable diagnostic tool for experimental hydrocephalus; also, it can be used to assess the progression of ventriculomegaly in animal models of hydrocephalus.

Meningitis is a serious public health problem due to its magnitude, its transmission potential, pathogenicity and social relevance. The clinic varies according to the patient's age and disease duration, and is characterized by nonspecific symptoms. The objective of this study is to outline the profile of meningitis epidemiology in Tocantins between 2010 and 2020, in order to highlight risk factors that favor the epidemic pattern of the pathology, which microregions need more attention and the diagnostic pattern. This is a descriptive, clinical-epidemiological research, with a retrospective cross-sectional study method. The data collection instrument used for this research was the Informatics Department of the Unified Health System (DATASUS). For theoretical foundation, data from scientific articles collected on the Scielo, Pubmed and Uptodate platforms were used. The present study observes that cases are more recurrent in the age group between 20 and 39 years, with a prevalence of males and the viral etiology of the disease. The main diagnostic method used is the clinical one, and when thinking about laboratory confirmation, culture is highlighted. Thus, it is necessary to formulate public policies, as well as strengthen existing ones. Keywords: Meningitis. Epidemiology. Health. Etiology. Profile.

Objectives Previous attempts to classify cancer cachexia (CC) have demonstrated limitations regarding stages and diagnostic criteria. This study aims to develop and validate a new staging system for CC in patients with incurable cancer. Methods This is an analysis of a database from a prospective cohort study of 1325 patients with advanced cancer referred for palliative care between 2016 and 2020. The cohort was randomly divided into two groups: Development (882 patients) and validation (443 patients) sets. A hierarchical cluster analysis was performed to distinguish different stages of CC in the development set. Next, the optimal cutoff points and ideal combinations of the most important factors associated with the CC groups (clusters) were ascertained. Finally, the relationship between the CC stages determined using the new system and body composition, quality of life, and overall survival was verified with the validation set. Results The new system classified CC into three stages: Precachexia (10.8%), cachexia (57.8%), and refractory cachexia (31.4%), based on a combination of percentage weight loss in the past 6 mo ( 26.4 kg/m2), and mid-upper-arm muscle area (≥38.0/≥35.5 or Conclusions This study presents a useful, valid system for CC staging in the clinical setting, and is also capable of predicting outcomes, including quality of life and overall survival.

To analyze the publications regarding the quality of life of women with cervical cancer. This is an integrative review performed in the indexed LILACS, MEDLINE and SCIELO databases. The descriptors “Quality of Life” AND “Cervical Neoplasms”, “Quality of Life” AND “Woman's Health” and “Woman's Health” AND “Cervical Neoplasms” were used, in which articles published in the period from 2010-2018 that met the inclusion criteria were selected. The research resulted in three articles in Lilacs, three in Medline, and five in Scielo, totaling 11 articles. The research used three questionnaires, such as EORTC QLQ-C30, WHOQOL-bref, and FACT-Cx. These instruments are the most widely used today to measure the quality of life and health conditions in broad aspects. It was observed that cervical cancer positively affects women's quality of life in social and emotional aspects. Quality of life, although with a positive evaluation, should encourage the formulation of public health policies aimed at improving this target audience's quality of life. The discovery of the disease brings several fears, including the thought of death. In addition, it has a physical and psychological impact on these women's lives. Analisar as publicações referentes à qualidade de vida das mulheres acometidas pelo câncer cervical. Trata-se de uma revisão integrativa realizada nas bases de dados indexadas LILACS, MEDLINE e SCIELO. Utilizou-se os descritores “Qualidade de vida” AND “Neoplasias do colo do útero”, “Qualidade de vida” AND “Saúde da Mulher” e “Saúde da Mulher” AND “Neoplasias do colo do útero”, na qual foram selecionados artigos publicados no período de 2010-2018 que atendessem aos critérios de inclusão. A pesquisa resultou em três artigos na Lilacs, três na Medline e cinco na Scielo, totalizando 11 artigos. As pesquisas utilizaram três questionários, tais como: EORTC QLQ-C30, WHOQOL-bref e FACT-Cx. Esses instrumentos são os mais utilizados na atualidade para mensurar a qualidade de vida e as condições de saúde em amplos aspectos. Observou-se que o câncer cervical afeta positivamente a qualidade de vida das mulheres nos aspectos sociais e emocionais. A qualidade de vida embora com a avaliação positiva nas mulheres deva ser incentivada à formulação de políticas públicas de saúde que visem à melhora da qualidade de vida desse público-alvo. A descoberta da doença traz vários receios, entre eles, o pensamento de morte que repercute de forma física e psicológica na vida dessas mulheres.

Umbilical hernia (UH) is one of the most frequent defects affecting pig production, however, it also affects humans and other mammals. UH is characterized as an abnormal protrusion of the abdominal contents to the umbilical region, causing pain, discomfort and reduced performance in pigs. Some genomic regions associated to UH have already been identified, however, no study involving RNA sequencing was performed when umbilical tissue is considered. Therefore, here, we have sequenced the umbilical ring transcriptome of five normal and five UH-affected pigs to uncover genes and pathways involved with UH development. A total of 13,216 transcripts were expressed in the umbilical ring tissue. From those, 230 genes were differentially expressed (DE) between normal and UH-affected pigs (FDR

Duplications of dosage sensitive sex-locus Xp21.2 including NR0B1 have been linked to 46,XY gonadal dysgenesis (GD) and their effects are attributed merely to increase gene dosage of NR0B1 (DAX1). Here we present a general mechanism how deletions, duplications, triplications or inversions with or without NR0B1 at Xp21.2 can lead to partial or complete GD by disrupting the cognate topological associated domain (TAD) in the vincinity of NR0B1. Our model is supported by three unrelated patients: two showing a 287kb overlapping duplication at the Xp21.2 locus upstream of NR0B1 containing CXorf21 and GK and one patient having a large new triplication of Xp21.2 as the most likely cause of GD. Whole Genome sequencing uncovered the exact structural rearrangements of the duplications and the triplication. Comparison with a previously published deletion upstream of NR0B1 revealed a common 35kb overlap between the deletion, our newly reported NR0B1 upstream duplications and the triplication as well as all other copy number variations (CNVs) at Xp21.2 reported so far. This overlap contains a strong CCCTC-binding factor (CTCF) binding site representing one boundary of the NR0B1 TAD. All three CNVs at Xp21.2 most likely disrupt this TAD boundary, which isolates NR0B1 from CXorf21 and GK and putatively results in GK and CXorf21 enhancer adoption and ensuing ectopic NR0B1 expression. As a result, the patients’ transcriptomes developed an intermediate expression pattern with both ovarian and testicular features and greatly reduced expression of spermatogenesis-related genes. This model not only allows better diagnosis of GD displaying CNVs at Xp21.2, but also gives deeper insight how spatiotemporal activation of developmental genes can be disrupted by reorganized TADs also in other rare diseases.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, chronic and systemic autoimmune disease generally with a more severe clinical phenotype than the adult-onset SLE. In both conditions, it is known that females are predominantly affected; therefore, the possible overlap of SLE and sex chromosomal abnormalities has attracted attention. Our case report describe the clinical manifestations and immunological profile of a Brazilian female with cSLE and trisomy X. The 22 year-old patient, diagnosed with cSLE at age of 11, present some features related to 47, XXX, such as difficulties at school and communication, although this was not enough to investigate for chromosome abnormalities. Cytoscan HD array screening allowed the comprehensive diagnosis for this patient. We also characterized her ancestral composition, showing that she has 6.2% higher African component than the mean from health subjects from the same geographical area. This report reinforces the role of the X chromosome dose effect for sex bias in SLE, as well as the importance of African ancestry composition in cLES. It also throws lights upon the application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data., Highlights • This report reinforces the role of the X chromosome dose effect for sex bias in SLE. • We highlight the importance of African ancestry composition in cSLE. • The application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data.

Patient-reported outcomes (PROs) are the patient’s assessment of their own health status, free from the interpretation of any third party, including healthcare providers. They convey valuable information on issues that are not easily assessed by healthcare providers, such as symptom frequency and burden or health-related quality of life, which are crucial to provide supportive care, and supplement the clinician perspective for treatment-related decisions. In oncology, their use has been associated with improved control over symptoms, overall survival, and patient satisfaction. PROs are increasingly being collected electronically (ePROs), allowing them to be transmitted to healthcare providers remotely and in real time.

Herein we evaluated the genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) from Bothrops pauloensis, on breast cancer cells. BnSP-6 was able to induce a higher cytotoxic and genotoxic activity in MDA-MB-231 cells, when compared to MCF10A (a non-tumorigenic breast cell line), suggesting that this protein presented a possible preference for cancer cells. BnSP-6 inhibited MDA-MB-231 proliferation at 24, 48 and 72 h. In addition, BnSP-6 induced significant increase in the percentage of TUNEL-positive cells, a marker of DNA damage. To obtain novel insight into the direct DNA damage interference in MDA-MB-231 survival and proliferation, we evaluated cell cycle progression. BnSP-6 produced a significant decrease in 2N (G1) and an increase in the G2/M phase and this capacity is likely related to the modulation of expression of progression cell cycle-associated genes (CCND1, CCNE1, CDC25A, CHEK2, E2F1, CDH-1 and NF-kB). Taken together, these results indicate that BnSP-6 induces DNA damage in breast cancer cells and is an attractive model for developing innovative therapeutic agents against breast cancer.

Submicroscopic deletions in chromosome 19 have been rarely reported. We reported a male patient presenting with neurodevelopmental delay and facial dysmorphisms with a de novo 19p13.11p13.12 deletion of approximately 1.4 Mb. To date, there are seven cases with deletions overlapping the 19p13.11-p13.12 region described in the literature. A region of 800 kb for branchial arch defects in the proximal region of 19p13.12, and another minimal critical region of 305 kb for hypertrichosis, synophrys, and protruding front teeth have been proposed previously. We suggest that the shortest region of overlap could be refined to an approximately 53 kb region shared within all patients, encompassing part of BRD4 and AKAP8L genes and the AKAP8 gene. Based on the genotype-phenotype correlation of the present case and cases with overlapping deletions described in the literature, it was possible to recognize a consistent phenotype characterized by microcephaly, ear abnormalities, rounded face, synophrys, arched or upwardly angulated eyebrows, short nose, anteverted nares, prominent cheeks, teeth abnormalities, and developmental delay.

Jalili syndrome (JS) is an autosomal recessive disease characterized by a combination of cone-rode retinal dytrophy (CRD) and amelogenesis imperfect (AI). Mutations in cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene cause JS. Here we described 2 families (3 members) affected by JS. In the first family, JS was caused by the homozygous p.Leu324Pro (c.971T > C) missense mutation and the affected patient developed both CRD and AI. In the second family, a specific combination of a compound heterozygous mutation was found – the p.Leu324Pro (c.971T > C) missense transition and the novel p.Tyr581* (c.1743C > G) nonsense mutation. The proband showed CRD and AI, but her father just developed eye alterations. Together, these findings suggest that the p.Leu324Pro mutation in homozygosis induces a complete phenotype with both CRD and AI, but in heterozygosis and in composition with the novel p.Tyr581* nonsense mutation in CNNM4 promotes variable clinical expressivity, particularly with lack of dental phenotypes. These different phenotypes could be explained by deletions affecting the proband's homologous allele, epistasia or interactions with environmental factors leading to residual activity of protein.

Craniofacial Microsomia (CFM) also known as Oculo-auriculo-vertebral Spectrum (OAVS) or Goldenhar Syndrome, presents wide phenotypic and etiological heterogeneity. It affects mainly the structures originated from the first and second pharyngeal arches. In addition, other major anomalies may also be found, including congenital heart diseases. In this study, we report a patient with distal deletion in the 22q11.2 region and a phenotype which resembles CFM. The proband is a girl, who presented bilateral preauricular tags, left auditory canal stenosis, malar hypoplasia, cleft lip and palate, mild asymmetry of soft tissue in face, congenital heart disease, intestinal atresia, annular pancreas and hydronephrosis. The genomic imbalances investigation by Multiplex Ligation-dependent Probe Amplification (MLPA) and Chromosomal Microarray Analysis (CMA) revealed a distal deletion of 1,048 kb at 22q11.2 encompassing the region from Low Copy Repeats (LCRs) D to E. We did review of the literature and genotype-phenotype correlation. This is the sixth case of distal 22q11.2 deletion resembling CFM and the second encompassing the region between LCRs D to E. All cases share some phenotypic signs, such as preauricular tags, facial asymmetry, cleft lip and palate, and congenital heart diseases. Candidate genes in this region have been studied by having an important role in pharyngeal arches developmental and in congenital heart diseases, such as HIC2, YPEL1and MAPK1/ERK2. This case corroborates the phenotypic similarity between 22q11.2 distal deletion and CFM/OAVS. It also contributes to genotype-phenotype correlation and reinforces that candidate genes for CFM, in the 22q11.2 region, might be located between LCRs D and E.

We investigated the possible beneficial effects that hyperbaric oxygen therapy could offer in different brain structures affected by ventriculomegaly in pup rats submitted to experimental hydrocephalus. Seven-day-old Wistar rats were submitted to hydrocephalus by intracisternal injection of 10% kaolin into the cisterna magna. The animals were divided into four groups: control (n = 5); control with HBOT (3ATA/2 h/day) (n = 5); untreated hydrocephalic (n = 10); hydrocephalic treated with HBOT (3ATA/2 h/day) (n = 10). The treatment with HBOT was performed daily for 14 days post-induction of hydrocephalus. To evaluate the response to treatment, behavioral tests (open field, Morris water maze, and activity monitor) were performed. After 14 days, the animals were euthanized, and the brain was removed for histological (hematoxylin-eosin and solochrome-cyanine) and immunohistochemical (GFAP and Ki-67) studies. The hyperbaric treatment, although not causing changes in ventricular enlargement, resulted in a significant improvement in the behavioral performance (p = 0.0001), with greater agility and exploration of the environment, preservation of spatial memory, and greater learning capacity (p = 0.0001). Through the immunohistochemical study, the astrocytic activity (glial fibrillary acidic protein) in the corpus callosum (p = 0.0001) and in the germinative matrix (p = 0.0033) was significantly reduced as compared to that in the H group. The results suggest that hyperbaric treatment bettered the behavioral performance and offered benefits to the structures affected by the ventricular increase helping to recover the brain damages. In this way, the HBOT it can be considered an adjuvant therapy for the treatment of hydrocephalus.