Hypertriglyceridemic Pancreatitis: Conventional Treatment Versus Therapeutic Plasma Exchange

Introdução:A pancreatite aguda (PA) por hipertrigliceridemia (HTG) pode ser tratada com troca plasmática terapêutica (TPT), com redução rápida dos valores de triglicerídeos. Contudo, não existem estudos comparativos definitivos que comprovem o real benefício desta terapêutica. Objetivo: Comparação dos métodos de tratamento (troca plasmática terapêutica versus convencional) em doentes com PA HTG, durante um período de 12 anos (2000-2012). Métodos: Estudo retrospetivo descritivo e inferencial de 37 doentes, avaliando: sexo, idade, antecedentes pessoais, gravidade, valores de TG e evolução consoante o tratamento (“TPT” ou terapêutica convencional “C”). Resultados: Os dois grupos TPT e C mostraram-se homogéneos quanto ao sexo (p = 0,647), idade (43,5 ± 9,74 anos TPT versus 45,30 ± 9,90 anos C; p = 0.320), pancreatite prévia (40% TPT vs 40,7% C; p = 1,0) alcoolismo crónico (50% TPT vs 70,4% C; p = 0,275) e gravidade pelo score de APACHE II (p = 0,054) e Ranson às 48 horas (p = 0,258). Dos doentes 45,95% apresentava mais de um fator de risco secundário para HTG. O grupo TPT apresentou maiores valores de TG à admissão: 4850 ± 2802 mg/dL vs 1845 ± 1858 mg/dL (p = 0,001). Não se verificaram diferenças na duração do internamento 14,2 ± 6,8 dias vs 13,5 ± 9,0 dias (p = 0,56) ou na taxa de mortalidade (p = 0,47). À data de alta a redução dos TG foi superior no grupo TPT: 4433,70 ± 2896,08 mg/dL - 91,41% vs 1582,95 ± 2051,06 mg/dL – 83,92% (p = 0,002). De referir seis intercorrências minor durante a troca plasmática terapêutica. Discussão/Conclusões: Apesar do viés de seleção (estudo retrospetivo), foi constatada uma maior redução dos TG por esta técnica. As intercorrências inerentes à técnica de troca plasmática terapêutica foram de simples resolução.info:eu-repo/semantics/publishedVersio

Dependence on Dectin-1 Varies With Multiple Candida Species

This is the final version. Available from Frontiers Media via the DOI in this recordFour Candida spp. (albicans, glabrata, tropicalis, parapsilosis) cause >95% of invasive Candida infections. C. albicans elicits immune responses via pathogen recognition receptors including C-type lectin-like receptors (CLRs). The CLR, Dectin-1 is important for host immunity to C. albicans and C. glabrata, however, whether Dectin-1 is important for host defense against C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the involvement of Dectin-1 in response to these four diverse Candida spp. We found that Dectin-1 mediates innate cytokine responses to these Candida spp. in a species- and cell-dependent manner. Dectin-1 KO mice succumbed to infection with highly virulent C. albicans while they mostly survived infection with less virulent Candida spp. However, Dectin-1 KO mice displayed increased fungal burden following infection with each Candida spp. Additionally, T cells from Dectin-1 KO mice displayed enhanced effector functions likely due to the inability of Dectin-1 KO mice to clear the infections. Together, these data indicate that Dectin-1 is important for host defense to multiple Candida spp., although the specific roles for Dectin-1 varies with different Candida spp.Wellcome TrustRoyal SocietyUK Dementia Research InstituteMRC Centre for Medical Mycolog

Pancreatite Hipertrigliceridémica: Tratamento Convencional Versus Troca Plasmática Terapêutica

Introduction: Acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) can be treated with therapeutic plasma exchange (TPE), resulting in rapid reduction of triglyceride level. However, there are no definitive comparative studies that prove the real benefits of this therapy. Objectives: Comparison of treatment methods (TPE versus conventional) in patients with HTG AP during a period of 12 years (2000-2012). Methods: Retrospective, descriptive and inferential analysis of 37 patients, evaluating: gender, age, personal pathologic history, severity of disease, HTG values and evolution depending on treatment with therapeutic plasma exchange (“TPE”) or with conventional therapy (“C”). Results: Both groups TPE and C demonstrated homogeneity considering gender (p = 0.647), age (43.5 ± 9.74 years TPE vs 45.30 ± 9.90 years C; p = 0.320), prior AP episode (40% TPE vs 40.7% C; p = 1.0), chronic alcohol consumption (50% TPE vs 70.4% C; p = 0.275) and severity disease scores: APACHE II (p = 0.054) and Ranson (p = 0.258). More than one secondary HTG risk factor was presented in 45.95% of patients . TPE group presented higher TG levels at admission: 4850 ± 2802 mg/dL vs 1845 ± 1858 mg/dL (p = 0.001). No significant statistical differences were observed considering length of hospital stay [14.2 ± 6.8 days vs 13.5 ± 9.0 days (p = 0.56)] or mortality rate (p = 0.47). At discharge, TG reduction was greater in TPE group: 4433.70 ± 2896.08 mg/dL – 91.41% vs 1582.95 ± 2051.06 mg/dL – 83,92% (p = 0.002). Six minor complications associated to TPE occurred. Discussion/Conclusion: Despite the selection bias (retrospective study), a greater TG reduction was observed with TPE technique. Complications associated with the technique were simple to resolveinfo:eu-repo/semantics/publishedVersio

Communication in Clinical Practice, the Perspective of Patients with Cancer: Translation of the PACE (Patient Assessment of Cancer Communication Experiences) Questionnaire to European Portuguese

Introduction: Communication in clinical practice is essential to healthcare quality, especially in Oncology. The Patient Assessment of Communication Experiences questionnaire evaluates the perspective of cancer patients towards communication and identifies areas that can be improved. This study consists in its translation and validation to European Portuguese, to identify these areas. Material and methods: We performed a descriptive, observational, cross-sectional study. The translation was conducted according to the World Health Organization's guidelines. We applied the questionnaires to a convenience sample, in patients under systemic antineoplastic treatment at the Day Hospital of Centro Hospitalar Universitário do Porto, between January and March 2020. We calculated the Cronbach's Alpha for each phase of care, the bivariate and multiple correlations and, for each question, the percentage of "non applicable" and most positive answers. Results: We had 100 participants. The instrument we obtained ha good internal consistency, but the classification of some questions does not correlate sufficiently with the global opinion about the experiences with communication in the respective phase. The diagnosis phase revealed a lower proportion of positive experiences, particularly in terms of receiving the bad news. Conclusion: This study translates and validates part of the communication assessment instrument PACE to the Portuguese language and elicits the necessity to invest in the phase of diagnosis and disclosure of bad news.ste trabalho não recebeu qualquer tipo de suporte financeiro de nenhuma entidade no domínio público ou privado

Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

Analysis of Insulin Doses of Chinese Type 2 Diabetic Patients with Intensive Insulin Treatment

BACKGROUND: To investigate the daily insulin doses and the ratio of basal insulin to total daily insulin in Chinese type 2 diabetic patients who received basal bolus insulin therapy. METHODOLOGY/PRINCIPAL FINDINGS: Totally 2480 patients prescribed with pre-meal bolus insulin and bedtime basal insulin were included. The mean daily insulin doses was 38.22 ± 14.92 IU/day, the mean daily insulin doses per weight was 0.58 ± 0.22 IU/kg, the mean bolus insulin dose was 0.44 ± 0.17 IU/kg and the mean basal insulin dose was 0.13 ± 0.08 IU/kg. The mean basal/total daily insulin ratio (BD/TDD) was 0.23 ± 0.08. In most patients (47.94%), the BD/TDD was between 0.20 and 0.30. Diabetic duration, BMI, HbA1c, fasting and postprandial blood glucose level were positively associated with daily insulin dose, while age was negatively associated with daily insulin dose. Diabetic duration, BMI, HbA1c, fasting blood glucose level, and using metformin were positively associated with BD/TDD ratio, while age, postprandial C peptide, postprandial blood glucose level and CRE level were negatively associated with BD/TDD ratio. CONCLUSIONS/SIGNIFICANCE: The daily insulin doses of intensive treatment in Chinese type 2 diabetic patients was 38.22 IU/day, the mean daily insulin doses per weight was 0.58 IU/kg, mean BD/TDD ratio was 0.23

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Strong CD4 T cell responses to Zika virus antigens in a cohort of Dengue virus immune mothers of congenital Zika virus syndrome infants

Background: There is an urgent need to understand the complex relationship between cross-reactive anti-viral immunity, disease susceptibility, and severity in the face of differential exposure to related, circulating Flaviviruses. Co-exposure to Dengue virus and Zika virus in Brazil is a case in point. A devastating aspect of the 2015-2016 South American Zika outbreak was the dramatic increase in numbers of infants born with microcephaly to mothers exposed to Zika virus during pregnancy. It has been proposed that this is more likely to ensue from Zika infection in women lacking cross-protective Dengue immunity. In this case series we measure the prevalence of Dengue immunity in a cohort of mothers exposed to Zika virus during pregnancy in the 2015-2016 Zika outbreak that gave birth to an infant affected by microcephaly and explore their adaptive immunity to Zika virus. Results: Fifty women from Sergipe, Brazil who gave birth to infants with microcephaly following Zika virus exposure during the 2015-16 outbreak were tested for serological evidence of Dengue exposure and IFNγ ELISpot spot forming cell (SFC) response to Zika virus. The majority (46/50) demonstrated Dengue immunity. IFNγ ELISpot responses to Zika virus antigens showed the following hierarchy: Env>NS1>NS3>C protein. Twenty T cell epitopes from Zika virus Env were identified. Responses to Zika virus antigens Env and NS1 were polyfunctional with cells making IFNγ, TNFα, IL-4, IL-13, and IL-10. In contrast, responses to NS5 only produced the immune regulatory TGFβ1 cytokine. There were SFC responses against Zika virus Env (1-20) and variant peptide sequences from West Nile virus, Dengue virus 1-4 and Yellow Fever virus. Conclusion: Almost all the women in our study showed serological evidence of Dengue immunity, suggesting that microcephaly can occur in DENV immune mothers. T cell immunity to Zika virus showed a multifunctional response to the antigens Env and NS1 and immune regulatory responses to NS5 and C protein. Our data support an argument that different viral products may skew the antiviral response to a more pro or anti-inflammatory outcome, with an associated impact on immunopathogenesis

Psychosocial correlates of physical activity in school children aged 8-10 years

Background: Understanding correlates of physical activity (PA) among children in different populations may contribute to fostering active lifestyles. This study considered gender differences in relationships between biologic (body mass index, BMI), demographic (socioeconomic sport status, SES) and psychosocial correlates of PA and level of PA in Portuguese primary school children. Methods: 683 children, aged 8–10 years, from 20 different elementary schools in northern Portugal were surveyed. Weight status was classified using International Obesity Task Force (IOTF) criteria for the BMI. Family SES was estimated from school records. PA level and psychosocial correlates (attraction to PA, perceived physical competence and parental socialization) were obtained with interview and standardized questionnaires, respectively. Sex-specific hierarchical multiple regression analyses (SPSS 18.0) were conducted and included two blocks of predictor variables (biologic and demographic, and psychosocial). Results: Level of PA was significantly higher in boys than girls. Enjoyment of participation in vigorous PA was positively associated with level of PA. Perceived acceptance by peers in games and sports and parental encouragement were positively and significantly related to PA in girls. Perceived physical competence was positively and significantly related to PA in boys. Weight status and SES were not associated with PA. Conclusions: Boys and girls differed in perceived attractiveness of PA and perceived physical competence, both of which influenced level of PA. Differences in perceptions may be important aspects of motivation for PA in school children