Delayed hemolytic transfusion reaction presenting as a painful crisis in a patient with sickle cell anemia

CONTEXT: Patients with sickle cell anemia (SCA) are frequently transfused with red blood cells (RBC). Recently, we reported that the calculated risk of RBC alloimmunization per transfused unit in Brazilian patients with SCA is 1.15%. We describe a delayed hemolytic transfusion reaction (DHTR) presenting as a painful crisis in a patient with SCA. CASE REPORT: A 35-year-old Brazilian female with homozygous SCA was admitted for a program of partial exchange transfusion prior to cholecystectomy. Her blood group was O RhD positive and no atypical RBC alloantibody was detected using the indirect antiglobulin technique. Pre-transfusional hemoglobin (Hb) was 8.7 g/dL and isovolumic partial exchange transfusion was performed using 4 units of ABO compatible packed RBC. Five days after the last transfusion she developed generalized joint pain and fever of 39°C. Her Hb level dropped from 12.0 g/dL to 9.3 g/dL and the unconjugated bilirrubin level rose to 27 mmol/L. She was jaundiced and had hemoglobinuria. Hemoglobin electrophoresis showed 48.7% HbS, 46.6% HbA1, 2.7% HbA2, and 2.0% HbF. The patient s extended RBC phenotype was CDe, K-k+, Kp(a-b+), Fy(a-b-), M+N+s+, Le(a+b-), Di(a-). An RBC alloantibody with specificity to the Rh system (anti-c, titer 1:16.384) was identified by the indirect antiglobulin test. The Rh phenotype of the RBC used in the last packed RBC transfusion was CcDEe. The patient was discharged, asymptomatic, 7 days after admission.CONTEXTO: Pacientes com anemia falciforme recebem com freqüência concentrados de glóbulos vermelhos (CGV). Recentemente, nós relatamos que o risco de alo-imunização eritrocitária por unidade transfundida em pacientes brasileiros com anemia falciforme é 1,15%. RELATO DE CASO: Nós descrevemos uma reação transfusional hemolítica tardia (RTHT) apresentando-se como uma crise dolorosa em um paciente com anemia falciforme.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Computational approaches in antibody-drug conjugate optimization for targeted cancer therapy

WOS: 000444683500007PubMed ID: 30068276Cancer has become one of the main leading causes of morbidity and mortality worldwide. One of the critical drawbacks of current cancer therapeutics has been the lack of the target-selectivity, as these drugs should have an effect exclusively on cancer cells while not perturbing healthy ones. In addition, their mechanism of action should be sufficiently fast to avoid the invasion of neighbouring healthy tissues by cancer cells. The use of conventional chemotherapeutic agents and other traditional therapies, such as surgery and radiotherapy, leads to off-target interactions with serious side effects. In this respect, recently developed target-selective Antibody-Drug Conjugates (ADCs) are more effective than traditional therapies, presumably due to their modular structures that combine many chemical properties simultaneously. In particular, ADCs are made up of three different units: a highly selective Monoclonal antibody (Mab) which is developed against a tumour-associated antigen, the payload (cytotoxic agent), and the linker. The latter should be stable in circulation while allowing the release of the cytotoxic agent in target cells. The modular nature of these drugs provides a platform to manipulate and improve selectivity and the toxicity of these molecules independently from each other. This in turn leads to generation of second-and third-generation ADCs, which have been more effective than the previous ones in terms of either selectivity or toxicity or both. Development of ADCs with improved efficacy requires knowledge at the atomic level regarding the structure and dynamics of the molecule. As such, we reviewed all the most recent computational methods used to attain all-atom description of the structure, energetics and dynamics of these systems. In particular, this includes homology modelling, molecular docking and refinement, atomistic and coarse-grained molecular dynamics simulations, principal component and cross-correlation analysis. The full characterization of the structure-activity relationship devoted to ADCs is critical for antibody-drug conjugate research and development.Fundacao para a Ciencia e a Tecnologia (FCT) Investigator programme [IF/00578/2014]; European Social Fund; Programa Operacional Potencial Humano; Marie Sklodowska-Curie Individual Fellowship MSCA-IF-2015 [MEMBRANEPROT 659826]; European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme [CENTRO-01-0145-FEDER-000008]; European Regional Development Fund (ERDF), COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation; Portuguese national funds via FCT [POCI-01-0145-FEDER-007440]; FCT [FCT-SFRH/BPD/97650/2013]; Fundacao para a Ciencia e Tecnologia (FCT), Portugal [UID/Multi/04349/2013]Irina S. Moreira acknowledges support by the Fundacao para a Ciencia e a Tecnologia (FCT) Investigator programme - IF/00578/2014 (co-financed by European Social Fund and Programa Operacional Potencial Humano), and a Marie Sklodowska-Curie Individual Fellowship MSCA-IF-2015 [MEMBRANEPROT 659826]. This work was also financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0145-FEDER-000008: Brain-Health 2020, and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-007440. Rita Melo acknowledges support from the FCT (FCT-SFRH/BPD/97650/2013). This work has been partially supported by the Fundacao para a Ciencia e Tecnologia (FCT), Portugal, through the UID/Multi/04349/2013 project in Centre for Nuclear Sciences and Technologies (C2TN)

Estudo Estatístico sobre Saldos de Caixa de Empresas Portuguesas

The cash balances of businesses have recently become one of the main topics of interest in the financial area. As a result of this interest, several studies and theories have been applied to this field, mainly to larger companies, and with a lesser application to the universe of small businesses. Portuguese business context is mainly composed by owner managed companies of the small businesses. The theoretical support that was considered most appropriate to back the analysis was the trade-off theory. The trade-off theory, in general terms, explains the amount of cash reported by companies on their balance sheets. This study is based on a sample of Portuguese manufacturing firms. It uses a methodology of econometric nature, based on models that were constructed to test if the tradeoff theory can explain the amount of cash held by these companies. The modeling considered four key variables (determinants) significant in the explanation of such amounts: the "net working capital", the "debt", the "size" and "cash flow". Moreover, after a closer analysis, the results indicate that there are significant differences when if there is or not an auditor that certifies the accounts of the companies is added as control.info:eu-repo/semantics/publishedVersio

Teachers' digital competences in higher education in Portugal and Spain

The potential of DTIC has brought new and emerging challenges to teachers, making it essential to acquire digital competences, especially in virtual learning environments and online technologies. In this sense, based on the DigCompEdu CheckIn self-assessment questionnaire, validated for the Portuguese population by earlier studies, this research aims to identify the most fragile and robust areas of digital competences of Portuguese and Spanish university teachers. The quantitative methodological approach emphasizes teachers' perception of their digital competences in three dimensions: teachers' professional competences, teachers' pedagogical competences and students' competences and involved 347 teachers from Portugal and Spain. The results show that teachers of the two institutions have an overall moderate level of digital proficiency-level B1 and B2-and that the differences encountered between Portuguese and Spanish teachers (for example, Portuguese teachers have level A2 in area 4-assessment-, while Spanish teachers are already at level B2) highlight the need to invest in specific training that may address specific frailties, and therefore allow for the promotion of their digital competences. Results relating to teaching experience and age show that there is no direct relation between either factor or being digitally competent. Regarding gender, results reveal that men had slightly better results than women. Overall, what the results show is the need for teachers to increase the level of digital competence through specific training, prepared according to the specificities of each institution, and the importance of developing public policies that prepare teachers for a more digital education

New insight on the solidification path of an alloy 625 weld overlay

AbstractNi-based alloys are a special class of engineering material with excellent corrosion resistance in harsh environments. However, microstructural changes due to the solidification, may result in solidification cracks and reduction in the corrosion resistance. Knowing the microchemical and microstructural evolutions during the solidification of these alloys is essential for the understanding of the relationship between the metallurgical aspects and the properties. This research presents a new insight on the solidification path of alloy 625 weld metals deposited by the TIG cold wire process on the C–Mn steel plates. After the welding, samples having been extracted and evaluated by the scanning electron microscope, transmission electron microscopy and energy dispersive X-ray spectroscopy techniques. The results showed the presence of two types of secondary phases, identified as Laves phase and complex nitride/carbide particles. Due to the presence of nitrides particles, stable in the solid state during the melting of the alloy, during the solidification it is noted the occurrence of a complex nitride/carbide precipitation. This implies in a new route to explain the solidification of the aforementioned alloy

Variation of the Anthropometric Index for pectus excavatum relative to age, race, and sex

OBJECTIVES: To determine possible variations in the Anthropometric Index for pectus excavatum relative to age, race, and sex in individuals free of thoracic wall deformities. METHODS: Between 2002 and 2012, 166 individuals with morphologically normal thoracic walls consented to have their chests and the perimeter of the lower third of the thorax measured according to the Anthropometric Index for pectus excavatum. The participant characteristics are presented (114 men and 52 women; 118 Caucasians and 48 people of African descent). RESULTS: Measurements of the Anthropometric Index for pectus excavatum were statistically significantly different between men and women (11-40 years old); however, no significant difference was found between Caucasians and people of African descent. For men, the index measurements were not significantly different across all of the age groups. For women, the index measurements were significantly lower for individuals aged 3 to 10 years old than for individuals aged 11 to 20 years old and 21 to 40 years old; however, no such difference was observed between women aged 11 to 20 years old and those aged 21 to 40 years old. CONCLUSION: In the sample, significant differences were observed between women aged 11 to 40 years old and the other age groups; however, there was no difference between Caucasian and people of African descent

Whole-body ARHGAP21-deficiency improves energetic homeostasis in lean and obese mice

Inhibition of Rab-GAP TBC1 domain family member 1 (TBC1D1) reduces body weight and increases energy expenditure in mice. Here, we assessed the possible involvement of GTPase activating protein 21 (ARHGAP21), a Rho-GAP protein, in energy homeostasis. Wild-type and whole-body ARHGAP21-haplodeficient mice were fed either chow or high-fat diet for 10 weeks. These mice were analyzed for body weight, food intake, voluntary physical activity, and energy expenditure by indirect calorimetry. Real-time PCR was performed to determine changes in the expression of hypothalamic-anorexic genes. Whole-body ARHGAP21-haplodeficient mice showed lower body weight and food intake associated with increased energy expenditure. These mice also showed higher expression of hypothalamic-anorexic genes such as POMC and CART. Our data suggest that the reduction in body weight of ARHGAP21-haplodeficient mice was related to alterations in the central nervous system. This suggests a new role for ARHGAP21 in energetic metabolism and prompts us to consider GAP protein members as possible targets for the prevention and treatment of obesity and related diseases10CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulonão tem2012/14993-9; 2015/12611-

Strongyloides stercoralis: a plea for action.

This paper argues that enough is now known on this neglected parasite to justify starting specific control measures

In Patients With Acute Myocardial Infarction, the Impact of Hyperglycemia as a Risk Factor for Mortality Is Not Homogeneous Across Age-Groups

OBJECTIVE To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AM I). RESEARCH DESIGN AND METHODS A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), >= 50 and <60 (n = 477),>= 60 and <70 (n = 545), >= 70 and <80 (n = 495), and years (n = 209). Hyperglycemia was defined as initial glucose >= 115 mg/dL. RESULTS The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001.), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5. CONCLUSIONS The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients