Inelastic neutron scattering investigation of the crystal field excitations of NdCo5

We present an inelastic neutron scattering study of the crystal electric field (CEF) levels in the intermetallic ferrimagnets RECo5 (RE=Nd and Y). In NdCo5, measurements at 5K reveal two levels at approximately 28.9 and 52.9 meV. Crystal-field calculations including the exchange field Bexc from the Co sites account for both of these, as well as the spectrum at temperatures above the spin-reorientation transition at ∼280 K. In particular, it is found that both a large hexagonal crystal field parameter A66(r6) and Bexc are required to reproduce the data, with the latter having a much larger value than that deduced from previous computational and experimental studies. Our study sheds light on the delicate interplay of terms in the rare-earth Hamiltonian of RECo5 systems, and is therefore expected to stimulate further experimental and computational work on the broader family of rare-earth permanent magnets

Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence

Estudos das indicações clínicas de esplenectomia em pacientes do Hospital Regional da Asa Norte no período de 2014 a 2018 / Studies of clinical indications for splenectomy in patients at the Asa Norte Regional Hospital from 2014 to 2018

O baço é um órgão intraperitoneal com importante função de hemocaterese e imunológica. A esplenectomia, retirada cirúrgica do baço, pode ser realizada em um contexto de urgência e emergência e por indicação clínica, que são controversas e podem ter a finalidade de cura, diagnóstico, estadiamento ou até mesmo paliativo. As consequências e complicações da esplenectomia podem ser gravíssimas, necessitando ser bem indicada, levando em consideração quadro clínico e complicações de doenças de base. Além disso, é imprescindível a vacinação contra S. pneumoniae, H. influenzae e N. Meningitidis, pelo estado imunológico que resta no esplenectomizado. O objetivo geral é: Estudar os casos de esplenectomia por indicação clínica no Hospital Regional da Asa Norte no período de janeiro de 2014 a dezembro de 2018. Os objetivos específicos são: (1) saber se vacinação profilática está sendo realizada no HRAN; (2) estudar as principais indicações clínicas da esplenectomia eletiva e complicações que esses pacientes desenvolveram decorrente de sua doença de base; e (3) estudar as diferentes faixas etárias dos pacientes nessa escolha terapêutica. A metodologia do estudo é uma análise retrospectiva, qualitativa e quantitativa dos prontuários de casos de esplenectomias eletivas. A amostra foi composta por pacientes de todas as idades que foram submetidos à esplenectomia eletiva por indicação clínica. As variáveis eleitas para investigação são: idade, sexo, ocupação, indicações clínicas para a retirada do baço, quadro clínico, via de acesso operatório, profilaxia para bactérias capsuladas, presença de complicações e desfecho clínico após procedimento. Foram incluídos 23 pacientes. Os resultados foram: em relação à idade dos pacientes, encontrado dos 0 aos 10 anos, 0% (N=0), dos 10 aos 20 anos 21,74% (N=5), dos 20 aos 30 anos 17,39% (N=4), dos 30 aos 40 anos 21,74% (N=5), dos 40 aos 50 anos 21,74% (N=5), dos 50 aos 60 anos 4,34% (N=1) e acima dos 60 anos de idade 13,04% (N=3). Predominantemente do sexo feminino 52,17% (N=12) dos pacientes, em comparação com 47,82% (N=11) do sexo masculino. Dados em relação à profissão de pacientes esplenectomizados de maneira eletiva são escassos. O quadro clínico dos pacientes incluídos no estudo se mostrou variável. Equimoses estavam presentes em 26,08% (N=6) dos casos. A trombocitopenia imune primária (PTI) corticodependente ou refratária se mostrou a principal indicação clínica para a esplenectomia, representando 21,73% dos casos (N=5). A plaquetopenia foi a complicação de doença de base mais encontrada, com porcentagem de 17,39% dos pacientes (N=4). Em relação à vacinação profilática, foi realizada antes da cirurgia em 39,13% (N=9) dos casos. A vacinação realizada após a cirurgia foi o caso de 13,04% (N=3) dos pacientes. Uma parcela de 30,43% (N=7) dos prontuários analisados não havia relato da realização ou não da vacinação profilática nos pacientes esplenectomizados.  Em 17,39% (N=4) dos casos, não foi realizada a vacinação profilática. Quanto às complicações cirúrgicas, cerca de 65,22% dos pacientes (N=15) não tiveram qualquer complicação cirúrgica. O desfecho clínico após a cirurgia foi de 91,30% (N=21) de alta hospitalar com acompanhamento ambulatorial.  Concluindo, ao realizar a revisão literária, percebe-se a quantidade reduzida de pesquisas e publicações a nível nacional e internacional, visto a importância da temática escolhida

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases

High tumour contamination of leukaphereses in patients with small cell carcinoma of the lung: a comparison of immunocytochemistry and RT-PCR

In small-cell lung carcinoma (SCLC) tumour cell contamination of leukaphereses is unknown. The present study was performed to define appropriate markers for reverse transcriptase polymerase chain reaction (RT-PCR), then to assess the contamination rate of leukaphereses and corresponding bone marrow samples. Immunocytochemistry (ICC) and RT-PCR methods were also compared. Among the 33 patients included, analyses were performed in 16 who had multiple leukaphereses and 17 who had only bone marrow. Leukapheresis products and bone marrow were analysed by ICC using several specific monoclonal antibodies against neural-cell adhesion molecule (N-CAM), epithelial glycoprotein (EGP-40) and cytokeratins (CK). Samples were also analyzed by RT-PCR for expression for N-CAM, synaptophysin, neuron-specific enolase, chromogranin, cytokeratin-18/-19, CEA, EGP-40, apomucin type 1 (MUC-1) and human endothelial cell-specific molecule (ESM-1). Using ICC staining, contaminating tumour cells were detected in 34% of leukaphereses (27% in patients with limited disease and 43% in those with extensive disease). N-CAM was the most reliable marker for detection of contamination. For RT-PCR, CK-19 and CEA were the only appropriate markers. Positive signal rate in leukaphereses increased to 78% (89% for patients with limited disease and 67% for extensive disease). In bone marrow, both techniques were in agreement whereas in leukaphereses, RT-PCR was better than ICC. A high rate of tumour cell contamination was demonstrated not only in bone marrow but also in leukaphereses from SCLC patients. The most appropriate technique was RT-PCR mainly in patients with limited disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport

Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation.</jats:p

Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians

The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%). This allele is uncommon in Afro-Brazilians (2.0%), rare in the Guarani Amerindians (0.4%) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7%) and R60S in the Afro-Brazilians (5.0%). A29S and L55Q present an impaired response to β-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4%) and Y68C (g.2964A > G) in Kaingang (10.3%). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations

Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection

Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis. Therefore, we sought to characterize, for the first time, the transcriptional profile of murine bone marrow-derived dendritic cells (DCs) at an early stage following their initial interaction with P. brasiliensis. DCs connect innate and adaptive immunity by recognizing invading pathogens and determining the type of effector T-cell that mediates an immune response. Gene expression profiles were analyzed using microarray and validated using real-time RT-PCR and protein secretion studies. A total of 299 genes were differentially expressed, many of which are involved in immunity, signal transduction, transcription and apoptosis. Genes encoding the cytokines IL-12 and TNF-α, along with the chemokines CCL22, CCL27 and CXCL10, were up-regulated, suggesting that P. brasiliensis induces a potent proinflammatory response in DCs. In contrast, pattern recognition receptor (PRR)-encoding genes, particularly those related to Toll-like receptors, were down-regulated or unchanged. This result prompted us to evaluate the expression profiles of dectin-1 and mannose receptor, two other important fungal PRRs that were not included in the microarray target cDNA sequences. Unlike the mannose receptor, the dectin-1 receptor gene was significantly induced, suggesting that this β-glucan receptor participates in the recognition of P. brasiliensis. We also used a receptor inhibition assay to evaluate the roles of these receptors in coordinating the expression of several immune-related genes in DCs upon fungal exposure. Altogether, our results provide an initial characterization of early host responses to P. brasiliensis and a basis for better understanding the infectious process of this important neglected pathogen