RELATO DE CASO: DOENÇA DE KAWASAKI

 A Doença de kawasaki foi descrita, em 1967, por um pediatra japonês, chamado Tomisaku Kawasaki. Definida como uma vasculite sistêmica aguda, o que significa que existe uma inflamação das paredes dos vasos sanguíneos, que pode evoluir para dilatação (aneurismas), principalmente, das artérias coronárias. A causa da doença é incerta, embora se suspeite que haja uma origem infecciosa. Os critérios diagnósticos incluem: febre que persiste além de cinco dias, congestão ocular bilateral não exsudativa, ressecamento de lábios e hiperemia de orofaringe com proeminência das papilas linguais, exantema polimorfo não vesicular que se inicia no tronco e se estende para membros, eritema e edema de mãos e pés que evolui para descamação periungueal, linfadenopatia cervical aguda não supurativa uni ou bilateral superior a 1,5 cm de diâmetro. Os critérios "completos" são: febre acima de cinco dias associada a quatro dos cinco critérios restantes ou a presença de febre e aneurisma coronariano associado a três dos demais critérios. O tratamento consiste no uso imunoglobulina, 2 g/kg em infusão contínua, e ácido acetil salicílico na dose de 100 mg/kg/dia, até o desaparecimento da febre e, a partir daí, 3 a 5 mg/kg/dia para manter o do efeito anti-trombótico até a normalização das plaquetas

Hanseníase: apresentação rara de comprometimento das 20 unhas - relato de caso / Hansen's disease: a rare presentation with the involvement of 20 nails – case report

Alterações ungueais são comuns na hanseníase e atribuídas a uma combinação de fatores como neuropatia, trauma, desordens vasculares e infecções.  Estima-se que 56% dos pacientes paucibacilares e 87% dos pacientes multibacilares apresentem alterações nas unhas, das quais as mais comuns são: hiperceratose ungueal, onicogrifose, onicorréxis, microníquia, anoníquia, sulcos de Beau, escleroníquia, melanoníquia longitudinal e pterígio ungueal inverso. Relatamos caso clínico de paciente que apresentava alterações ungueais da Hanseníase na sua manifestação mais rara de acometimento das 20 unhas e o diagnóstico diferencial com o líquen plano ungueal, a candidíase mucocutânea, a paquidermoperiostose, e outras neuropatias periféricas como no Diabetes Mellitus.

Estimating the costs of air pollution to the National Health Service and social care : An assessment and forecast up to 2035

BACKGROUND: Air pollution damages health by promoting the onset of some non-communicable diseases (NCDs), putting additional strain on the National Health Service (NHS) and social care. This study quantifies the total health and related NHS and social care cost burden due to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in England. METHOD AND FINDINGS: Air pollutant concentration surfaces from land use regression models and cost data from hospital admissions data and a literature review were fed into a microsimulation model, that was run from 2015 to 2035. Different scenarios were modelled: (1) baseline 'no change' scenario; (2) individuals' pollutant exposure is reduced to natural (non-anthropogenic) levels to compute the disease cases attributable to PM2.5 and NO2; (3) PM2.5 and NO2 concentrations reduced by 1 μg/m3; and (4) NO2 annual European Union limit values reached (40 μg/m3). For the 18 years after baseline, the total cumulative cost to the NHS and social care is estimated at £5.37 billion for PM2.5 and NO2 combined, rising to £18.57 billion when costs for diseases for which there is less robust evidence are included. These costs are due to the cumulative incidence of air-pollution-related NCDs, such as 348,878 coronary heart disease cases estimated to be attributable to PM2.5 and 573,363 diabetes cases estimated to be attributable to NO2 by 2035. Findings from modelling studies are limited by the conceptual model, assumptions, and the availability and quality of input data. CONCLUSIONS: Approximately 2.5 million cases of NCDs attributable to air pollution are predicted by 2035 if PM2.5 and NO2 stay at current levels, making air pollution an important public health priority. In future work, the modelling framework should be updated to include multi-pollutant exposure-response functions, as well as to disaggregate results by socioeconomic status

Innervation of the nipple-areolar complex after reduction mammaplasty: a histological study

INTRODUCTION: The periareolar dermal release maneuver in mammoplasty promotes better mobility of the nipple-areola complex. However, there are doubts on possible nerve damages in this kind of topography. This quantitative analysis compared the nerve branches density from the medial, lateral and caudal side-flow of the nipple-areola complex (NAC). METHODS: This was a prospective study. The study included 26 women who have undergone a mammaplasty reduction using the Pitanguy's classic technique. The dermis fragments collected from the medial, lateral and caudal sides were properly prepared and subjected to a histological study in order to determine the nerve branches density in each studied sides. RESULTS: Of 26 studied patients, 42.3% had a higher nerve branches density in the lateral side; 38.5%, on the medial side and 19.2% on the caudal side. The statistical analysis used to evaluate whether there was a predominance of one side where the dermis has been sectioned showed that the proportion comparison test was not significant (p = 0.304). CONCLUSION: The comparative analysis has shown that there is no preponderance of nerve density in any periareolar dermis side

The Pro-Oncogenic Adaptor CIN85 Acts as an Inhibitory Binding Partner of Hypoxia-Inducible Factor Prolyl Hydroxylase 2

The EGFR adaptor protein, CIN85, has been shown to promote breast cancer malignancy and hypoxia-inducible factor (HIF) stability. However, the mechanisms underlying cancer promotion remain ill defined. Here we show that CIN85 is a novel binding partner of the main HIF-prolyl hydroxylase, PHD2, but not of PHD1 or PHD3. Mechanistically, the N-terminal SRC homology 3 domains of CIN85 interacted with the proline-arginine-rich region within the N-terminus of PHD2, thereby inhibiting PHD2 activity and HIF degradation. This activity is essential in vivo, as specific loss of the CIN85-PHD2 interaction in CRISPR/Cas9-edited cells affected growth and migration properties, as well as tumor growth in mice. Overall, we discovered a previously unrecognized tumor growth checkpoint that is regulated by CIN85-PHD2 and uncovered an essential survival function in tumor cells by linking growth factor adaptors with hypoxia signaling. Significance: This study provides unprecedented evidence for an oxygen-independent mechanism of PHD2 regulation that has important implications in cancer cell survival.Peer reviewe

Daily risk of adverse outcomes in patients undergoing complex lesions revascularization: a subgroup analysis from the RAIN-CARDIOGROUP VII study (veRy thin stents for patients with left mAIn or bifurcatioN in real life)

Introduction: Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known.Methods: All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint.Results: 2745 patients were included, mean age 68 ± 11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer.Conclusions: The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications

De novo mutations in GRIN1 cause extensive bilateral polymicrogyria

Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-d-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-d-aspartate receptor signalling in the pathogenesis of polymicrogyria