Journals
2015 PO
Bárbara Raquel Agostini · Maria Tatiana De Lima Rocha Félix · Edson Marcos De Godoy Palomares
A Ginástica Rítmica (GR) é caracterizada como uma modalidade competitiva olímpica que demonstra um alto domínio das capacidades coordenativas por intermédio de pequenos aparelhos. A exteriorização da demonstração dessas atividades ocorre através das séries de competição. O treinamento da modalidade, em nível competitivo, torna-se uma tarefa diária e constante, que demanda a necessidade de enfrentamento de desafios que exigem uma condição psicológica eficaz que varia de acordo com aspectos individuais e situacionais. Dessa forma, o presente estudo tem por objetivo avaliar os fatores estressores no período pré-competitivo em um grupo de atletas de GR. Caracterizou-se como uma pesquisa de campo do tipo descritiva e transversal. A amostra foi composta por 22 atletas de GR participantes do Campeonato Cearense de 2013, com idades entre 12 e 14 anos. Como instrumento utilizou-se o teste “Lista de Sintomas de Estresse Pré-Competitivo Infanto-Juvenil (LSSPCI)”. Para análise dos dados foi utilizado o tipo ‘moda’ de estatística descritiva. Concluímos que o controle do estresse desencadeado pela competição é um fator primordial no aprimoramento técnico, físico e psicológico de atletas de GR. O medo de perder a competição e a ansiedade pré-competitiva apresentaram-se como os principais sintomas estressores relatados.Palavras-chave: ginástica, estresse, treinamento esportivo, fisiologia, esporte.
Journals
2015 PO
Gustavo Gastão Davanzo · Fernando Canova · Dora Maria Grassi Kassisse
A hidratação adequada permanece sendo uma barreira a se superar. Por conta disso, neste estudo, objetivamos apresentar a resposta do organismo frente às adversidades do ambiente, clima seco, úmido, frio ou calor, estando o indivíduo em atividade ou em repouso. Como complemento para entendimento dos fenômenos fisiológicos envolvidos com a [des]- [re]-[hiper]-hidratação, apresenta-se o sistema renal contextualizando sua relação com o sistema cardiovascular e endócrino. São apresentados conceitos básicos como compartimentos líquidos do organismo, osmolaridade plasmática e urinária, funções dos rins, estímulos da sede. Também é abordado o ajuste fino que o corpo faz frente a situações de excesso (hiper-hidratação) ou falta de água no organismo (desidratação), dando especial atenção para o exercício físico e a importância da [re]-hidratação adequada. Terminando com orientações para que o atleta tenha uma melhora no desempenho tomando para sua rotina hábitos simples e saudáveis.Palavras-chave: hidratação, sais minerais, atividade física.
Journals
2015 EN
Dimitrios Papaioannou · Anna-Maria Strothmeyer · Marcus Duehren-von Minden
+6 more
Antigen receptors of B cells (BCR) exhibit a virtually unlimited repertoire, created by V(D)J recombination through combinatorial and junctional diversity of genetic elements in B-precursor cells. B cells further increase the antigen affinity of their BCR through somatic hypermutation (SHM). VDJ
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Journals
2015 EN
Morena Caira · Anna Candoni · Luisa Verga
+41 more
Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient's risk category and improve targeted prophylactic strategies. (Clinicaltrial.gov: NCT01315925)
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Journals
2015 EN
Cristina Bugarin · Jolanda Sarno · Chiara Palmi
+17 more
Genomic rearrangements of the cytokine receptor-like factor 2 (CRLF2) gene,[1][1],[2][2] which is part of the thymic stromal lymphopoietin receptor (TSLPR), result in overexpression of CRLF2 itself leading to JAK2-mediated activation of STAT5, which regulates cell proliferation, survival, and
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Journals
2015 EN
Marina Pereira Colella · Erich Vinícius De Paula · João Agostinho MachadoNeto
+5 more
Hemoglobin SC disease is a very prevalent hemoglobinopathy; however, very little is known about this condition specifically. There appears to be an increased risk of thromboembolic events in hemoglobin SC disease, but studies evaluating the hemostatic alterations are lacking. We describe the findings of a cross-sectional observational study evaluating coagulation activation markers in adult patients with hemoglobin SC, comparing them with those in sickle cell anemia patients and healthy controls. A total of 56 hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients was taking hydroxyurea. Hemoglobin SC patients had a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (P<0.01). Hemoglobin SC patients had lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (P<0.05). Markers of endothelial activation (soluble thrombomodulin and soluble vascular cell adhesion molecule-1) and inflammation (tumor necrosis factor-alpha) were both significantly elevated in hemoglobin SC patients when compared to controls, being as high as the levels seen in patients with sickle cell anemia. Overall, in hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in hemoglobin SC disease: retinopathy and osteonecrosis. In summary, our results demonstrate that hemoglobin SC patients have a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia.
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Journals
2015 EN
Jessica Bordini · Maria Teresa Sabrina Bertilaccio · Maurilio Ponzoni
+5 more
Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients.
Ferrata Storti Foundation
Journals
2015 EN
Carolina Moreno · Marco Montillo · Panayiotis Panayiotidis
+32 more
We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062.
Ferrata Storti Foundation
Journals
2015 EN
Isabella Spinello · Maria Teresa Quaranta · Rosa Paolillo
+6 more
High expression of the chemokine receptor 4, CXCR4, associated with a negative prognosis in acute myeloid leukemia, is related to hypoxia. Because CXCR4 expression is under the post-transcriptional control of microRNA-146a in normal and leukemic monocytic cells, we first investigated the impact of hypoxia on microRNA-146a and CXCR4 expression during monocytopoiesis and in acute monocytic leukemia. We then analyzed the effects of hypoxia on drug sensitivity of CXCR4-expressing leukemic cells. We found that microRNA-146a is a target of hypoxia-inducible factor-1α or -2α in relation to the stage of monocytopoiesis and the level of hypoxia, and demonstrated the regulation of the microRNA-146a/CXCR4 pathway by hypoxia in monocytes derived from CD34(+) cells. Thus, in myeloid leukemic cell lines, hypoxia-mediated control of the microRNA-146a/CXCR4 pathway depends only on the capacity of hypoxia-inducible factor-1α to up-regulate microRNA-146a, which in turn decreases CXCR4 expression. However, at variance with normal monocytic cells and leukemic cell lines, in acute monocytic leukemia overexpressing CXCR4, hypoxia up-modulates microRNA-146a but fails to down-modulate CXCR4 expression. We then investigated the effect of hypoxia on the response of leukemic cells to chemotherapy alone or in combination with stromal-derived factor-1α. We found that hypoxia increases stromal-derived factor-1α-induced survival of leukemic cells by decreasing their sensitivity to anti-leukemic drugs. Altogether, our results demonstrate that hypoxia-mediated regulation of microRNA-146a, which controls CXCR4 expression in monocytic cells, is lost in acute monocytic leukemia, thus contributing to maintaining CXCR4 overexpression and protecting the cells from anti-leukemic drugs in the hypoxic bone marrow microenvironment.
Ferrata Storti Foundation
Journals
2015 EN
Michael Auerbach · J W Adamson · Andreas J. Bircher
+14 more
Anemia is one of the world’s most common disorders. In 2010, global anemia prevalence was 32.9%, affecting over 2.2 billion people, and iron deficiency the most common of the causes.1 Oral iron, while inexpensive and effective when taken and tolerated, is frequently associated with unpleasant gastrointestinal side-effects, resulting in high rates of non-adherence. Furthermore, in conditions such as inflammatory bowel disease, end-stage renal disease, heavy uterine bleeding, hereditary hemorrhagic telangiectasia, and following major and bariatric surgery, oral iron may be ineffective due to its inability to keep up with losses or may be harmful by worsening the underlying pathology or by causing significant gastrointestinal side-effects. Under these circumstances, intravenous iron administration is the repletion route of choice. Currently, five formulations are available in the United States and six in Europe. Based on the overwhelming amount of published evidence, intravenous iron is nearly universally effective, with serious adverse events being very rare, estimated to be less than 1:200,000 administrations.2 Nonetheless, there is an ongoing prejudice against the use of parenteral iron largely based on experience with earlier preparations that are no longer available and which were associated with unacceptably high rates of anaphylactic reactions. Adding to these concerns is the use of spontaneous reporting of serious adverse events, a proscribed method of determining relative safety profiles of different formulations,3 and corroborated by a recent guidance document by the European Medicines Agency stating post-marketing spontaneous reports “cannot be used to detect any differences in the safety profile of the different iron medicines”.4Therefore, the seventeen co-authors of this commentary wish to challenge the conclusions drawn in a recent Prescrire publication, which makes recommendations based on inferences that are inaccurate and clinically imprudent.5In a recent criticism of the use of intravenous iron and a warning against one product, ostensibly less safe than others, the authors omitted all prospective and intrainstitutional observational studies that have come to the opposite conclusion (see below).6,7 An example is found in the concluding paragraph: “Given the risk of serious hypersensitivity reactions as well as other adverse effects, the use of intravenous iron-containing products should be limited to situations in which the benefits clearly outweigh the harm. Iron sucrose is the best choice, as other products do not have a more favorable harm-benefit balance. The decision to keep iron dextran on the market is absurd: it protects the manufacturer while exposing patients to unnecessary risks”. In contradistinction, an examination of published evidence suggests the above statements are simply incorrect. Below we highlight this evidence.Shortly after recombinant erythropoietin was approved for correction of anemia in patients on dialysis, it became apparent that intravenous iron was necessary for an optimal erythropoietic response. High molecular weight iron dextran (HMWID, Imferon®), which is no longer available, was the only formulation used at first. While infrequent serious reactions were observed, safety concerns were raised. Then, in 1991, Imferon® was removed from market, but serendipitously at the same time, low molecular weight iron dextran (LMWID, INFeD® in the United States and CosmoFer® in Europe) was approved for use. The literature is rife with safety and efficacy reports, and serious adverse events with LMWID are extremely rare. It was not until 1996, when a HMWID (Dexferrum®), which is also no longer available, was released, that serious adverse events became frequent; numerous publications support this view.8 With HMWID now withdrawn from the market, there is no credible evidence supporting either increased efficacy or decreased safety with any of the remaining available formulations compared to any other. As a result, the US FDA wrote a letter to the American distributors of iron sucrose, which is now in the public domain, ordering them to remove all advertising claiming any safety advantage with iron sucrose.Three prospective studies, a meta-analysis and an intrainstitutional observational study at the Harvard Medical School hospitals6,7 report no significant efficacy or safety differences. A comparison of ferric carboxymaltose and LMWID in second and third trimester gravidas reported safety and efficacy without serious adverse events in either group.9 Supporting their conclusions in a single institution observational study using a prospective model for the integrated safety analysis, 1266 total dose infusions (1000 mg in 1 h) of low molecular weight iron dextran were given to 888 patients, 162 of whom were pregnant, intolerant of oral iron, or in whom oral iron was ineffective or contraindicated.10 No serious adverse events were observed. Low molecular weight iron dextran is the formulation currently being used for the first prospective study of intravenous iron in the second or third trimester of pregnancy in the US under an FDA IND (#114696). In a preliminary analysis of 57 of 60 planned subjects having completed study treatment to date, no serious adverse events have been observed. It should be noted that the total number of subjects included in these studies is small, and important adverse effects and relative differences in adverse events could be present that are not reflected in the studies.In a prospective, controlled, randomized trial of 162 patients, comparing iron sucrose and ferumoxytol in patients with chronic kidney disease, the authors reported no difference in safety or efficacy.11 The only prospective trial to report a significant safety difference between any of the formulations compared the now unavailable HMWID to ferric carboxymaltose and erroneously concluded, without differentiating the high and low molecular weight formulations, that ferric carboxymaltose had a safety advantage over iron dextran.12 Corroborating data were recently published in a large meta-analysis of studies carried out in thousands of subjects who received intravenous iron.13In an editorial accompanying the article, Prescrire reported that “there is no advantage to the use of iron dextran over iron sucrose and the risks of using iron dextran far outweigh the benefits”. Not only is the statement without evidence to support it, but a replacement dose of intravenous iron sucrose requires four or five clinical visits compared to one visit with an infusion of 1000 mg of LMWID (a commonly used method approved in Europe but still off label in the US). The same advantage can be achieved with ferric carboxymaltose (approved as 1000 mg in 15 min in Europe and 750 mg in the US), iron isomaltoside (Europe only), and ferumoxytol (approval limited to 510 mg per visit).Pre-medication with antihistamines is frequently administered without any data supporting their use. There are even published data suggesting that the majority of adverse events seen with intravenous iron, when intravenous diphenhydramine is used as pre-medication, are due to the pre-medication and mistakenly attributed to the intravenous iron.14 Antihistamines can cause flushing, hypotension, somnolence, and supraventricular tachycardia, prompting inappropriate intervention and the conversion of a minor reaction to a severe one. In contrast, there is a syndrome occurring in approximately 1:200 patients, consisting of arthralgias, myalgias or flushing, without associated hypotension, tachycardia, tachypnea, wheezing, stridor or periorbital edema. No intervention is necessary.15 After symptoms abate, re-challenge is appropriate. In the rare patient who reacts twice, the iron formulation should be changed. Antihistamines are inappropriate since measured tryptase levels after these reactions have always been normal.16 While post-marketing, spontaneous adverse event reporting can provide useful and important information, one simply cannot determine relative safety among formulations. Without head-to-head trials, such conclusions lack validity.Parenteral iron is not just ‘superior’, it is a necessity since oral iron is ineffective in a number of clinical settings. Overstating the avoidance of intravenous iron is not only counterproductive but potentially harmful. Limiting its use will dramatically increase erythropoietin usage as well as transfusions and their associated complications. Essentially, all interpretable evidence supports the equivalent efficacy and safety of all of the current intravenous iron formulations. If minor infusion reactions occur with one formulation, switching to another is appropriate and safe.
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