Unilateral segmental presentation and a novel EPHB4 gene variant in capillary malformation-arteriovenous malformation type 2.

Capillary malformation-arteriovenous malformation is a rare autosomal dominant disorder associated with EPHB4 loss-of-function mutations. We report the unique presentation of a 6-year-old girl with multiple capillary malformations in a unilateral segmental distribution affecting the right hemiface, right upper chest, and right arm associated with overgrowth. Targeted next-generation sequencing on a tissue sample revealed a novel heterozygotic variant in the EPHB4 gene (NM_004444.5 (EPHB4): c.715T>A, p.[Cys239Ser]). This case highlights a distinct presentation of CM-AVM type 2 and showcases a new variant in EPHB4 not previously reported in the literature.

Early detection of interstitial lung disease in rheumatic diseases: A joint statement from the Portuguese Pulmonology Society, the Portuguese Rheumatology Society, and the Portuguese Radiology and Nuclear Medicine Society.

INTRODUCTION: Interstitial lung disease (ILD) contributes significantly to morbidity and mortality in connective tissue disease (CTD). Early detection and accurate diagnosis are essential for informing treatment decisions and prognosis in this setting. Clear guidance on CTD-ILD screening, however, is lacking. OBJECTIVE: To establish recommendations for CTD-ILD screening based on the current evidence. METHOD: Following an extensive literature research and evaluation of articles selected for their recency and relevance to the characterization, screening, and management of CTD-ILD, an expert panel formed by six pulmonologists from the Portuguese Society of Pulmonology, six rheumatologists from the Portuguese Society of Rheumatology, and six radiologists from the Portuguese Society of Radiology and Nuclear Medicine participated in a multidisciplinary discussion to produce a joint statement on screening recommendations for ILD in CTD. RESULTS: The expert panel achieved consensus on when and how to screen for ILD in patients with systemic sclerosis, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, idiopathic inflammatory myopathies and systemic lupus erythematous. CONCLUSIONS: Despite the lack of data on screening for CTD-ILD, an expert panel of pulmonologists, rheumatologists and radiologists agreed on a series of screening recommendations to support decision-making and enable early diagnosis of ILD to ultimately improve outcomes and prognosis in patients with CTD.

Contact sensitization in pediatric patients with atopic dermatitis: a purpose for a new patch testing serie for the Portuguese population.

Summary: Atopic dermatitis is a common illness in pediatric age. Children with atopic dermatitis are prone to develop cutaneous sensitization due to skin barrier dysfunction and immune dysregulation. Recent studies have shown a higher prevalence of certain allergens, which identification may be clinically relevant and have implications for atopic dermatitis management. Considering the most prevalent and relevant allergens based on a retrospective analysis of 145 pediatric patients, 44.1% (n = 63) with atopic dermatitis, and comparing the positive results, we propose the application of an adapted baseline series with the most relevant 20 allergens for the Portuguese pediatric population with atopic dermatitis with recommendation for an evaluation of allergic contact dermatitis.

Zap1 is required for Candida glabrata response to fluconazole.

The increasing prevalence of fluconazole-resistant clinical isolates of Candida spp. strongly hinders the widespread use of the drug. To tackle this problem, great efforts have been made to fully understand the fungal response to fluconazole. In this work, we show that the role of Zap1 in Candida glabrata goes beyond regulating yeast adaptation to zinc deficiency. In line with our previous observation that deletion of ZAP1 makes yeast cells more sensitive to fluconazole, we found that the mutant CgΔzap1 accumulates higher levels of the drug, which correlates well with its lower levels of ergosterol. Surprisingly, Zap1 is a negative regulator of the drug efflux transporter gene CDR1 and of its regulator, PDR1. The apparent paradox of drug accumulation in cells where genes encoding transporters relevant for drug extrusion are being overexpressed led us to postulate that their activity could be impaired. In agreement, Zap1-depleted cells present, in addition to decreased ergosterol levels, an altered composition of membrane phospholipids, which together should impact membrane function and impair the detoxification of fluconazole. Overall, our study brings to light Zap1 as an important hub in Candida glabrata response to fluconazole.

The accessory heads of the muscles flexor pollicis longus and flexor digitorum profundus (Gantzer muscle) - An anatomical study in Brazilian cadavers.

An important accessory anatomical variation, exclusively human, and related to the muscular ventres of the flexor pollicis longus and flexor digitorum profundus is frequently denominated Gantzer. These variations have close relations with the anterior interosseous nerve (AIN), which provides, for many authors, by direct compression, one of the rare neuropathic syndromes. In this work, thirty-four forearms were dissected from the collections of the Medical School of the Federal University of Minas Gerais and the Department of Basic Sciences of the Federal University of Juiz de Fora, with a prevalence of 50% of the 34 forearms studied for the Gantzer muscle. The muscle relationship was mainly with the flexor pollicis longus muscle and only one occurrence related to the flexor digitorum profundus muscle, described as a rare occurrence of unilateral double formation of Gantzer muscle. Bilaterality was observed in 88.23% of the findings and the dominant innervation for this muscle variation occurred in 82.35% by the anterior interosseous nerve (AIN). The type morphological in all forms found was the fusiform, with 10.5cm of total length and an average of 0.3cm in diameter and all related, as origin, in the medial aspect of the coronoid process of the ulna, next to the origin of the flexor digitorum superficialis muscle. Our work largely reflected the findings of most publications and, considering the controversy of the occurrence of a compressive neuropathy, the data were not sufficient, from a strictly anatomical point of view, to confirm or refute the hypothesis.

A data-driven model for COVID-19 pandemic - Evolution of the attack rate and prognosis for Brazil.

We introduce a compartmental model SEIAHRV (Susceptible, Exposed, Infected, Asymptomatic, Hospitalized, Recovered, Vaccinated) with age structure for the spread of the SARAS-CoV virus. In order to model current different vaccines we use compartments for individuals vaccinated with one and two doses without vaccine failure and a compartment for vaccinated individual with vaccine failure. The model allows to consider any number of different vaccines with different efficacies and delays between doses. Contacts among age groups are modeled by a contact matrix and the contagion matrix is obtained from a probability of contagion p c per contact. The model uses known epidemiological parameters and the time dependent probability p c is obtained by fitting the model output to the series of deaths in each locality, and reflects non-pharmaceutical interventions. As a benchmark the output of the model is compared to two good quality serological surveys, and applied to study the evolution of the COVID-19 pandemic in the main Brazilian cities with a total population of more than one million. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of We also estimate the attack rate, the total proportion of cases (symptomatic and asymptomatic) with respect to the total population, for all Brazilian states since the beginning of the COVID-19 pandemic. We argue that the model present here is relevant to assessing present policies not only in Brazil but also in any place where good serological surveys are not available.

El impacto de la pandemia de COVID-19 en la activación del Código Ictus y en el tiempo desde el inicio de los síntomas hasta la llegada al hospital en un centro de ictus portugués / The impact of COVID-19 pandemic in stroke code activation and time from symptom onset to hospital arrival in a Portuguese comprehensive stroke centre

Introduction: Coronavirus disease 2019 (COVID-19) impacted emergency services worldwide.Aim: We aimed to evaluate COVID-19 effect on the number of stroke code activations and timings during the first two months of the pandemic. Material and methods: We reviewed the stroke code database of a single comprehensive stroke centre in Portugal for the number of activations through 2019-2020. We compared the pathway timings between March and April 2020 (COVID-19 period) and the homologous months of the previous four years (pre-COVID-19 period), whilst using February as a control. Results: Monthly stroke code activation rates decreased up to 34.2% during COVID-19 pandemic. Compared to the pre-COVID-19 period, we observed an increase in the time from symptom onset to emergency call, with a significant number of patients waiting more than four hours (March 20.8% vs. 6.8%, p = 0.034; April 23.8% vs. 6%, p = 0.01); as well as an increase in the time from symptom onset to hospital arrival (March: median 136 minutes [IQR 106-410] vs. 100 [IQR 64-175], p = 0.001; April: median 188 [IQR 96-394] vs. 98 [IQR 66-168], p = 0.007). No difference between both periods was found concerning in-hospital times, patient characteristics, stroke/mimic diagnosis, stroke severity, and mortality. Conclusion: COVID-19 related factors probably reduced healthcare services utilization, and delayed emergency calls and hospital arrival after stroke onset. These highlight the importance of health education to improve the effectiveness of medical assistance. The preservation of in-hospital times validates the feasibility of the protected stroke code protocol.(AU)

Introducción: La enfermedad por coronavirus 2019 (COVID-19) provocó un considerable impacto mundial en los servicios de emergencia. Objetivo: Se pretende evaluar el efecto de la COVID-19 sobre el número y los tiempos de activaciones del Código Ictus en el comienzo de la pandemia. Material y métodos. Se revisó la base de datos del Código Ictus de un centro de ictus de Portugal entre 2016 y 2020. Se compararon los tiempos de activación entre marzo y abril de 2020 (período COVID-19) y los meses homólogos de los cuatro años anteriores, mientras que se utilizó febrero como control. Resultados: Las tasas mensuales de activación disminuyeron hasta el 34,2% durante la pandemia. En comparación con el período previo, se observó un aumento del tiempo desde los síntomas hasta la llamada de emergencia, con un aumento de pacientes que esperaron más de cuatro horas (marzo: 20,8 frente a 6,8%, p = 0,034; abril: 23,8 frente a 6%, p = 0,01) y del tiempo desde los síntomas hasta la llegada al hospital –marzo: mediana de 136 minutos (rango intercuartílico [RIC]: 106-410) frente a 100 (RIC: 64-175), p = 0,001; abril: mediana de 188 (RIC: 96-394) frente a 98 (RIC: 66-168), p = 0,007–. No hubo diferencias en los tiempos de internamiento, las características de los pacientes, el diagnóstico de ictus/stroke mimics, la gravedad del ictus o la mortalidad. Conclusión: Los factores relacionados con la COVID-19 redujeron la utilización de los servicios sanitarios y retrasaron las llamadas de emergencia y el tiempo de llegada al hospital. Esto demuestra la importancia de la educación sanitaria para mejorar la eficacia de la asistencia médica.(AU)

The impact of COVID-19 pandemic in stroke code activation and time from symptom onset to hospital arrival in a Portuguese comprehensive stroke centre. / El impacto de la pandemia de COVID-19 en la activación del Código Ictus y en el tiempo desde el inicio de los síntomas hasta la llegada al hospital en un centro de ictus portugués.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) impacted emergency services worldwide. AIM: We aimed to evaluate COVID-19 effect on the number of stroke code activations and timings during the first two months of the pandemic. MATERIAL AND METHODS: We reviewed the stroke code database of a single comprehensive stroke centre in Portugal for the number of activations through 2019-2020. We compared the pathway timings between March and April 2020 (COVID-19 period) and the homologous months of the previous four years (pre-COVID-19 period), whilst using February as a control. RESULTS: Monthly stroke code activation rates decreased up to 34.2% during COVID-19 pandemic. Compared to the pre-COVID-19 period, we observed an increase in the time from symptom onset to emergency call, with a significant number of patients waiting more than four hours (March 20.8% vs. 6.8%, p = 0.034; April 23.8% vs. 6%, p = 0.01); as well as an increase in the time from symptom onset to hospital arrival (March: median 136 minutes [IQR 106-410] vs. 100 [IQR 64-175], p = 0.001; April: median 188 [IQR 96-394] vs. 98 [IQR 66-168], p = 0.007). No difference between both periods was found concerning in-hospital times, patient characteristics, stroke/mimic diagnosis, stroke severity, and mortality. CONCLUSION: COVID-19 related factors probably reduced healthcare services utilization, and delayed emergency calls and hospital arrival after stroke onset. These highlight the importance of health education to improve the effectiveness of medical assistance. The preservation of in-hospital times validates the feasibility of the protected stroke code protocol.

TITLE: El impacto de la pandemia de COVID-19 en la activación del Código Ictus y en el tiempo desde el inicio de los síntomas hasta la llegada al hospital en un centro de ictus portugués.Introducción. La enfermedad por coronavirus 2019 (COVID-19) provocó un considerable impacto mundial en los servicios de emergencia. Objetivo. Se pretende evaluar el efecto de la COVID-19 sobre el número y los tiempos de activaciones del Código Ictus en el comienzo de la pandemia. Material y métodos. Se revisó la base de datos del Código Ictus de un centro de ictus de Portugal entre 2016 y 2020. Se compararon los tiempos de activación entre marzo y abril de 2020 (período COVID-19) y los meses homólogos de los cuatro años anteriores, mientras que se utilizó febrero como control. Resultados. Las tasas mensuales de activación disminuyeron hasta el 34,2% durante la pandemia. En comparación con el período previo, se observó un aumento del tiempo desde los síntomas hasta la llamada de emergencia, con un aumento de pacientes que esperaron más de cuatro horas (marzo: 20,8 frente a 6,8%, p = 0,034; abril: 23,8 frente a 6%, p = 0,01) y del tiempo desde los síntomas hasta la llegada al hospital ­marzo: mediana de 136 minutos (rango intercuartílico [RIC]: 106-410) frente a 100 (RIC: 64-175), p = 0,001; abril: mediana de 188 (RIC: 96-394) frente a 98 (RIC: 66-168), p = 0,007­. No hubo diferencias en los tiempos de internamiento, las características de los pacientes, el diagnóstico de ictus/stroke mimics, la gravedad del ictus o la mortalidad. Conclusión. Los factores relacionados con la COVID-19 redujeron la utilización de los servicios sanitarios y retrasaron las llamadas de emergencia y el tiempo de llegada al hospital. Esto demuestra la importancia de la educación sanitaria para mejorar la eficacia de la asistencia médica.

The effect of thoracic manipulation on pulmonary function in swimmers / Efecto de la manipulación torácica en la función pulmonar de nadadores / Efeito da manipulação torácica na função pulmonar em nadadores

Objective: Spinal manipulation has been used to improve respiratory function in healthy individuals. However, it has been observed that there are no studies in the context of sports activities. The objective of this study was to analyse the effect of thoracic spinal manipulation on forced vital capacity, forced expiratory volume in one second and maximal voluntary ventilation in swimmers.Method: A randomized controlled crossover study consisting of 21 swimmers, divided into two groups (Intervention vs Control), aged 16 – 24y, where forced vital capacity, forced expiratory volume in one second and maximal voluntary ventilation were measured in five evaluation moments: at baseline and, 1 minute, 10 minutes, 20 minutes and 30 minutes following the thoracic spinal manipulation procedures.Results: ANOVA tests showed no statistically significant differences for forced vital capacity (p = 0.35) and forced expiratory volume in one second (p = 0.25) among the five evaluation moments. With the maximal voluntary ventilation there was a statistically significant (p = 0.02) reduction, observed between baseline (86.00 litres) and at 10 minutes (79.29 litres) and 30 minutes (76.24 litres). No significant differences were observed between the results of intervention and control groups.Conclusions: In the current study no significant differences were observed in pulmonary function after thoracic spinal manipulation. Future research efforts should examine the effects of different manual therapy techniques and treatment protocols. (AU)

Objetivo: La manipulación espinal se ha utilizado para mejorar la función respiratoria en individuos sanos. Sin embargo, se ha observado que no hay estudios en el contexto de las actividades deportivas. El objetivo de este estudio fue analizar el efecto de la manipulación de la columna torácica en la capacidad vital forzada, el volumen espiratorio forzado en el primer segundo y la ventilación voluntaria máxima en nadadores.Método: Un estudio cruzado controlado aleatorio que consta de 21 nadadores, divididos en dos grupos (Intervención vs Control), de 16 a 24 años, donde se midieron la capacidad vital forzada, el volumen espiratorio forzado en el primer segundo y la ventilación voluntaria máxima en cinco momentos de evaluación: al inicio y, 1 minuto, 10 minutos, 20 minutos y 30 minutos después de los procedimientos de la manipulación de la columna torácica.Resultados: Las pruebas ANOVA no mostraron diferencias estadísticamente significativas para la capacidad vital forzada (p = 0.35) y el volumen espiratorio forzado en el primer segundo (p = 0.25) entre los cinco momentos de evaluación. Con la ventilación voluntaria máxima hubo una reducción estadísticamente significativa (p = 0.02), observada entre lo inicio (86.00 litros) y a los 10 minutos (79.29 litros) y 30 minutos (76.24 litros). No se observaron diferencias significativas entre los resultados de los grupos de intervención y control.Conclusiones: En el presente estudio, no se observaron diferencias significativas en la función pulmonar después de la manipulación de la columna torácica. Futuros estudios de investigación deberían examinar los efectos de diferentes técnicas de terapia manual y protocolos de tratamiento. (AU)

Objetivo: A manipulação da coluna vertebral tem sido utilizada para melhorar a função respiratória em indivíduos saudáveis. No entanto, observou-se que não existem estudos no contexto de atividades desportivas. O objetivo deste estudo foi analisar o efeito da manipulação da coluna torácica na capacidade vital forçada, volume expiratório forçado no primeiro segundo e ventilação voluntária máxima em nadadores.Método: Estudo aleatorizado controlado cruzado composto por 21 nadadores, divididos em dois grupos (Intervenção vs Controlo), com idades entre 16 e 24 anos, onde a capacidade vital forçada, volume expiratório forçado no primeiro segundo e ventilação voluntária máxima foram medidos em cinco momentos de avaliação: no início e, 1 minuto, 10 minutos, 20 minutos e 30 minutos após os procedimentos da manipulação da coluna torácica.Resultados: Os testes ANOVA não mostraram diferenças estatisticamente significativas para a capacidade vital forçada (p = 0.35) e volume expiratório forçado no primeiro segundo (p = 0.25) entre os cinco momentos da avaliação. Com a ventilação voluntária máxima houve uma redução estatisticamente significante (p = 0.02), observada entre o início (86.00 litros) e as medições aos 10 minutos (79.29 litros) e 30 minutos (76.24 litros). Não foram observadas diferenças significativas entre os resultados dos grupos intervenção e controlo.Conclusões: No presente estudo, não foram observadas diferenças significativas na função pulmonar após a manipulação da coluna torácica. Futuras pesquisas devem examinar os efeitos de diferentes técnicas de terapia manual e protocolos de tratamento. (AU)

Inadequacy of Vitamin D Nutritional Status in Individuals with Metabolically Unhealthy Obesity Phenotype: The Relevance of Insulin Resistance.

PURPOSE: The aim was to evaluate 25(OH)D serum concentrations in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) and its relation with biochemical and clinical parameters in both groups according to homeostatic model assessment-insulin resistance (HOMA-IR) definition of the obesity phenotypes. PATIENTS AND METHODS: Descriptive cross-sectional study was conducted with individuals of both genders. Anthropometric data [waist circumference, body mass index (BMI)] and metabolic parameters: blood glucose, glycated hemoglobin, insulin, lipid profile, calcium, phosphorus, parathyroid hormone (PTH) and high-sensitivity c-reactive protein (hs-CRP) and (25(OH)D) were obtained. The cutoff points for vitamin D deficiency and insufficiency were ≤20 and 21-29 ng/mL, respectively. Individuals were classified as MUHO according to HOMA-IR≥2.5. RESULTS: This study comprised 232 individuals with obesity (BMI≥35 kg/m2; 42.6±4.7 kg/m2). The MUHO phenotype was observed in 76.7% of the population. The mean values of glucose (P<0.001), insulin (P<0.001), HOMA-IR (P<0.001), and triglycerides (P=0.049) were significantly higher in the MUHO than in the MHO phenotype group. The mean value of 25(OH)D showed a significant difference between the MHO and MUHO phenotype groups (P=0.011). Additionally, and in line, lower mean 25(OH)D values were found in the MUHO vs the MHO phenotype group in the deficiency (14.5±3.6 ng/mL/17.1±2.7 ng/mL, P=0.004) and insufficiency (24.5±2.9 ng/mL/25.7±2.6 ng/mL, P=0.077) 25(OH)D groups. An increase of 1 ng/mL of vitamin D increased in 1.051 (95% CI= 1.011-1.093, P=0.012) the odds of the healthy phenotype. CONCLUSION: The highest prevalence of inadequacy of serum concentrations of 25(OH)D and greater severity of this deficiency in individuals with MUHO phenotype were observed. Low serum concentrations of this vitamin were associated, mainly, with insulin resistance. Monitoring the nutritional status of vitamin D in individuals with obesity that present with MUHO phenotype may contribute to minimize the occurrence and aggravation of diseases associated with obesity.

A copper(II)-binding triazole derivative with ionophore properties is active against Candida spp.

Invasive fungal infections (IFIs) are life threatening and existing antifungal drugs are not completely effective due to undesirable side effects and resistance emergence. Azoles are often the treatment of choice for IFIs and growing evidence suggests that copper can act synergistically with these drugs. In this work, we designed a compound bringing together azole and copper(II)-binding groups and studied the molecular mechanisms underlying its biological toxicity. Our results show that both the compound, 4, and its copper(II) complex, Cu.4, are active against Candida spp. We found that Cu.4 acts as a copper(II) ionophore, which results in the intracellular accumulation of reactive oxygen species (ROS), whereas compound 4 is an iron chelator and exerts its toxicity by decreasing iron bioavailability. Interestingly, while 4 is not very toxic to macrophages or HeLa cells, Cu.4 significantly affects their viability. Overall, this work provides evidence of how copper can be combined with azoles to deregulate copper homeostasis, opening new horizons for the development of bifunctional antifungals.

Plasmonic photothermal microneedle arrays and single needles for minimally-invasive deep in-skin hyperthermia.

We report, for the first time, crosslinked polymeric microneedle (MN) arrays and single needles (2 mm and 4.5 mm length) coated with gold nanorods (GnRs) to induce deep hyperthermia in a 3 mm-thickness skin model upon near infrared (NIR) laser irradiation. Using excised neonatal porcine skin as tissue model, it was seen that insertion capabilities of single prototypes were not affected by the coating, as around 80% of their length was inserted before and after coating. Insertion of MN arrays dropped from 74% to 55%, which could be attributed to a less sharp structure after the coating process. Nonetheless, GnRs-coated MN arrays achieved the highest increase in temperature in the skin model: over 15 °C after only 15 s of NIR laser irradiation (808 nm, 2 W cm-2). Surprisingly, removal of MN arrays after irradiation left no detectable polymer or plasmonic material behind, confirming the enhanced safety and minimally-invasive potential of this device for future biomedical applications of deep in skin hyperthermia.

Influence of temperature-humidity index on conception rate of Nelore embryos produced in vitro in northern Brazil.

Considering the high temperatures that the tropical climate provides to most of Brazil and the effects of thermal stress on reproductive processes, the objective of the present study was to analyze, in the warmer months of 2016, conception rates of Nelore bovine embryos in Acre state. For this purpose, oocytes were aspirated (ultrasound-guided follicular aspiration), matured, fertilized with Nelore bull semen, cultured for 6 days, and then the embryos were transferred to crossbred recipients. Pregnancy diagnosis was performed 30 and 60 days after embryo transfer. Meteorological data were obtained at www.inmet.gov.br to generate temperature-humidity index (THI). The data from the conception rates and periods of the year were submitted to the chi-square test at 5% probability to verify independence. Regression analysis was used to verify the relationship between THI and gestation rate. There was a strong relationship between conception rates and THI values, verified by an increase in conception rates as THI values were reduced and a decrease when THI reached the highest value. Our findings demonstrated a negative effect of heat stress in conception rates of crossbred cows in northern Brazil.

Diretrizes da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria para sibilância e asma no pré-escolar / Guidelines of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics for wheezing and asthma in preschool children

A asma é uma das doenças crônicas de maior frequência na infância. Parcela significativa de crianças com asma desenvolve sintomas nos primeiros anos de vida, mas nem sempre a sua confirmação diagnóstica é fácil. Outras causas de sibilância que podem gerar confusão diagnóstica, além da complexidade para a obtenção de medidas objetivas, tais como a realização de provas de função pulmonar nessa faixa etária, são justificativas para esse fato. Especialistas na abordagem desses pacientes, da Associação Brasileira de Alergia e Imunologia e da Sociedade Brasileira de Pediatria, após revisão extensa da literatura pertinente elaboraram esse documento, onde são comentados os possíveis agentes etiológicos, prevalência, diagnóstico diferencial, assim como tratamento e prevenção da sibilância e asma em pré-escolares.

Asthma is one of the most frequent chronic diseases in childhood. A significant portion of children with asthma develop symptoms in the first years of life, but diagnostic confirmation is not always easy. The difficulty is justified by other causes of wheezing that can generate diagnostic confusion, and by the complexity involved in obtaining objective measures ­ such as pulmonary function tests ­ in this age group. Specialists with expertise in the approach of these patients, from both the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics, after extensive review of the pertinent literature, developed this document to discuss possible etiological agents, prevalence, differential diagnosis, as well as treatment and prevention of wheezing and asthma in preschool children.

Portuguese recommendations for the prevention, diagnosis and management of primary osteoporosis - 2018 update.

BACKGROUND: Advances in osteoporosis (OP)case definition, treatment options, optimal therapy duration and pharmacoeconomic evidence in the national context motivated the Portuguese Society of Rheumatology (SPR) to update the Portuguese recommendations for the diagnosis and management of osteoporosis published in 2007. METHODS: SPR bone diseases' working group organized meetings involving 55 participants (rheumatologists, rheumatology fellows and one OP specialist nurse) to debate and develop the document. First, the working group selected 11 pertinent clinical questions for the diagnosis and management of osteoporosis in standard clinical practice. Then, each question was investigated through literature review and draft recommendations were built through consensus. When insufficient evidence was available, recommendations were based on experts' opinion and on good clinical practice. At two national meetings, the recommendations were discussed and updated. A draft of the recommendations full text was submitted to critical review among the working group and suggestions were incorporated. A final version was circulated among all Portuguese rheumatologists before publication and the level of agreement was anonymously assessed using an online survey. RESULTS: The 2018 SPR recommendations provide comprehensive guidance on osteoporosis prevention, diagnosis, fracture risk assessment, pharmacological treatment initiation, therapy options and duration of treatment, based on the best available evidence. They attained desirable agreement among Portuguese rheumatologists. As more evidence becomes available, periodic revisions will be performed. Target audience and patient population: The target audience for these guidelines includes all clinicians. The target patient population includes adult Portuguese people. Intended use: These recommendations provide general guidance for typical cases. They may not be appropriate in all situations - clinicians are encouraged to consider this information together with updated evidence and their best clinical judgment in individual cases.