Functional capacity and risk of injury in CrossFit practitioners measured through smartphone apps.

BACKGROUND: CrossFit is a high intensity functional training that tends to challenge physical limits. The objectives of this study were to assess functional capacity, prevalence and risk of injury in CrossFit practitioners. METHODS: This cross-sectional, observational and prospective study evaluate the rate of injuries that occurred in CrossFit practitioners in the last 12 months and their functional capacities. The sample was given for convenience, with a total of 22 participants. Functional capacities and risk of injury were measured by functional tests using PHAST and Clinometer applications. The prevalence of injuries was cataloged using the Nordic Musculoskeletal Questionnaire. RESULTS: 5% of the injuries occurred in the neck; 9% in shoulder, hip, thighs, ankles and feet; 14% in the lumbar spine and knees. The worst functional results were for the shoulder medial rotation ROM test, where 86-95% of the athletes were classified as "Bad"; the dorsiflexion ROM test also performed poorly in 68% of athletes. CONCLUSION: This study shows that the CrossFit practice suggests that the injury prevalence is relatively low, affecting mainly knees, lumbar spine, wrists and hands. However, the risk of injuries shown by the functional musculoskeletal assessment is higher, especially in the shoulder and ankle, and it is important for the practitioner to realize a specific functional assessment before starting training.

Sputum interleukin-6 level as a marker of severity during acute chest syndrome in children with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of morbimortality in sickle cell disease (SCD). In this prospective observational study, we investigated sputum interleukin-6 (IL-6) level as an ACS severity marker during 30 ACS episodes in 26 SCD children. Sputum IL-6 levels measured within the first 72 h of hospitalisation for ACS were significantly higher in patients with oxygen requirement ≥2 L/min, ventilation (invasive and/or non-invasive) length ≥5 days, bilateral and/or extensive opacities on chest X-ray or erythrocytapheresis requirement. Sputum IL-6 could serve as an ACS severity marker to help identify patients requiring targeted anti-inflammatory treatments such as tocilizumab.

Oral famotidine reduces the plasma level of soluble P-selectin in children with sickle cell disease.

Plasma histamine levels are increased in patients with sickle cell disease (SCD), potentially promoting endothelial P-selectin expression and vaso-occlusion via histamine type 2 (H2) receptors. We conducted a prospective, non-comparative, single-centre study to determine whether famotidine, a H2 receptor antagonist, reduces P-selectin expression in SCD children. The median plasma P-selectin level was significantly reduced after 29 days of oral famotidine (53.2 ng/mL [IQR: 46.7-63.4] vs. 69.9 ng/mL [IQR: 53.6-84.2], median difference -10.2 ng/mL [IQR: -21.8 to -2.7], p = 0.005) in 28 patients. No effect was observed on other adhesion molecules, inflammation or haemolysis markers, except decreased reticulocyte count. No adverse events deemed related to famotidine were observed. Randomized controlled trials are now needed to assess the efficacy of famotidine in preventing vaso-occlusion in SCD.

Dramatic efficacy of cannabidiol on refractory chronic pain in an adolescent with sickle cell disease.

Here, we report a dramatic efficacy of cannabidiol in an adolescent with SCD suffering from chronic pain refractory to other analgesics, with complete regression of chronic pain and rapid plasma histamine level normalization after treatment.

Successful treatment of JAK1-associated inflammatory disease.

BACKGROUND: Gain-of-function variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy, and eosinophilia. OBJECTIVES: This study sought to describe the clinical and immunological characteristics associated with a new gain-of-function variant of JAK1 and report the therapeutic efficacy of Janus kinase (JAK) inhibition. METHODS: The investigators identified a family affected by JAK1-associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signaling was studied by flow and mass cytometry in patients' cells at basal state or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with 1 of 2 JAK inhibitors: either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period. RESULTS: Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhea, disseminated calcifying fibrous tumors, and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected, tested patients. Hyper-phosphorylation of STAT3 was found in 5 of 6 patients tested. Treatment of patients' cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation. CONCLUSIONS: Patients with this new JAK1 gain-of-function pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumors. The disease, which appears to be linked to STAT3 hyperactivation, was well controlled under treatment by JAK inhibitors in adult patients.

A deep dive into future therapies for microcytic anemias and clinical considerations.

INTRODUCTION: Microcytic anemias (MA) have frequent or rare etiologies. New discoveries in understanding and treatment of microcytic anemias need to be reviewed. AREAS COVERED: Microcytic anemias with a focus on the most frequent causes and on monogenic diseases that are relevant for understanding biocellular mechanisms of MA. All treatments except gene therapy, with a focus on recent advances. PubMed search with references selected by expert opinion. EXPERT OPINION: As the genetic and cellular backgrounds of dyserythropoiesis will continue to be clarified, collaboration with bioengineering of treatments acting specifically at the protein domain level will continue to provide new therapies in hematology as well as oncology and neurology.

Mast cell-mediated inflammation relies on insulin-regulated aminopeptidase controlling cytokine export from the Golgi.

BACKGROUND: On activation, mast cells rapidly release preformed inflammatory mediators from large cytoplasmic granules via regulated exocytosis. This acute degranulation is followed by a late activation phase involving synthesis and secretion of cytokines, growth factors, and other inflammatory molecules via the constitutive pathway that remains ill defined. OBJECTIVE: We investigated the role for an insulin-responsive vesicle-like endosomal compartment, marked by insulin-regulated aminopeptidase (IRAP), in the secretion of TNF-α and IL-6 in mast cells and macrophages. METHODS: Murine knockout (KO) mouse models (IRAP-KO and kit-Wsh/sh) were used to study inflammatory disease models and to measure and mechanistically investigate cytokine secretion and degranulation in bone marrow-derived mast cells in vitro. RESULTS: IRAP-KO mice are protected from TNF-α-dependent kidney injury and inflammatory arthritis. In the absence of IRAP, TNF-α and IL-6 but not IL-10 fail to be efficiently secreted. Moreover, chemical targeting of IRAP endosomes reduced proinflammatory cytokine secretion. Mechanistically, impaired TNF-α export from the Golgi and reduced colocalization of vesicle-associated membrane protein (VAMP) 3-positive TNF-α transport vesicles with syntaxin 4 (aka Stx4) was observed in IRAP-KO mast cells, while VAMP8-dependent exocytosis of secretory granules was facilitated. CONCLUSION: IRAP plays a novel role in mast cell-mediated inflammation through the regulation of exocytic trafficking of cytokines.

Cursos técnicos de habilitação em Educação Física de 2° grau: estudos de caso no Rio de Janeiro no período de 1970 a 1990 / Technical courses in Physical Education at the high school: case studies in Rio de Janeiro from 1970 to 1990 / Cursos tecnicos en Educación Física en la escuela secundária: studios de caso en Rio de Janeiro de 1970 hasta 1990

Presente no sistema universitário em âmbito federal para civis desde 1939, a formação em Educação Física conviveu com outros espaços de formação por longo tempo. Um desses espaços consiste nos cursos técnicos de habilitação de professores em Educação Física de 2° grau (atual ensino médio). Nesse sentido, que papel teria o curso técnico de formação de professores em Educação Física? Para responder tal questão, a pesquisa teve como objetivo específico analisar os cursos técnicos de 2° grau de formação de professores em Educação Física e a sua mediação com a formação profissional nas décadas de 1970, 1980 e 1990. Como material empírico foi realizada a análise documental de matrizes curriculares, portarias governamentais e legislações federais e estaduais (Rio de Janeiro) sobre educação, além da visita a quatro instituições de educação básica no Estado do Rio de Janeiro que, em outros tempos, ofertavam o referido curso.

Present in the university system at the federal level since 1939, it has lived with other spaces of formation for a long time. One of these spaces consists of the technical courses of habilitation of teachers in Physical Education at the level of 2nd degree (current high school). In this sense, what role would the technical course of teacher training in Physical Education have? In order to answer this question, the research had the specific objective of analyzing the technical courses of 2nd degree of teacher training in Physical Education and its mediation with professional training in the 1970s, 1980s and 1990s. As empirical material the analysis was performed documentary of curricular matrices, governmental ordinances and federal and state legislations (Rio de Janeiro) on education, besides the visitto four institutions of basic education in the Stateof Rio de Janeiro that offered the referred course at the time.

Presente en el sistema universitario a nivel federal para civiles desde 1939, convivió durante mucho tiempo com otros espacios de formación. Uno de estos espacios consiste en cursos técnicos para La formación de profesores de Educación Física en Secundaria. En este sentido, ¿qué papel tendría el curso técnico para La formación de profesores de Educación Física? Para responder a esta interrogante, La investigación tuvo como objetivo específico analizar los cursos técnicos de 2° grado de formación de profesores de Educación Física y su mediación com La formación profesional en las décadas de 1970, 1980 y 1990. Como material empírico, El análisis fue documental de matrices curriculares, ordenanzas gubernamentales y legislación federal y estatal (Río de Janeiro) sobre educación, además de la visita a cuatro instituciones de educación básica del Estado de Río de Janeiro que, em otros tiempos, ofrecieron este curso.

Quantum Statistical Complexity Measure as a Signaling of Correlation Transitions.

We introduce a quantum version for the statistical complexity measure, in the context of quantum information theory, and use it as a signaling function of quantum order-disorder transitions. We discuss the possibility for such transitions to characterize interesting physical phenomena, as quantum phase transitions, or abrupt variations in correlation distributions. We apply our measure on two exactly solvable Hamiltonian models: the 1D-Quantum Ising Model (in the single-particle reduced state), and on Heisenberg XXZ spin-1/2 chain (in the two-particle reduced state). We analyze its behavior across quantum phase transitions for finite system sizes, as well as in the thermodynamic limit by using Bethe Ansatz technique.

HbS promotes TLR4-mediated monocyte activation and proinflammatory cytokine production in sickle cell disease.

Monocytes are considered crucial actors of inflammation in sickle cell disease (SCD), being responsible for an increased production of proinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. Although a role of free heme released by intravascular hemolysis has been suspected, the mechanisms underlying monocyte activation in patients with SCD remain unknown. Using purified human hemoglobin (Hb), we demonstrate herein, that cell-free HbS, unlike HbA or heme, is responsible for a major enhancement in the expression of proinflammatory cytokines by human monocytes. This effect was found mediated by direct interaction with the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex, resulting in the activation of both the nuclear factor-κB (NF-κB) and type I interferon pathways. In Townes SCD mice, injection of HbS, unlike HbA, was responsible for an increased production of proinflammatory cytokines, which was prevented by the TLR4 inhibitor, TAK-242. Our results reveal a novel mechanism of monocyte activation and systemic inflammation in SCD, which opens new promising therapeutic perspectives targeting the HbS-TLR4 interaction.

Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1.

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by restoring antitumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Neuropilin-1 (NRP1) is a transmembrane glycoprotein required for nervous system and angiogenesis embryonic development, also expressed in immune cells. We hypothesized that NRP1 could be an immune checkpoint co-receptor modulating CD8+ T cells activity in the context of the antitumor immune response. Here, we show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T cells, cooperates and enhances PD-1 activity. In mice, CD8+ T cells specific deletion of Nrp1 improves anti-PD1 antibody antitumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T cells predicts poor outcome of patients treated with anti-PD1. NRP1 is a promising target to overcome resistance to anti-PD1 therapies.

Erythrocytosis associated with IgA nephropathy.

BACKGROUND: Erythrocytosis is a hematological disorder usually related to hematopoietic stem cell somatic mutations. However, unexplained erythrocytosis remains frequent. In this study, we evaluated the involvement of IgA1, a regulator of erythropoiesis also implicated in IgA nephropathy (IgAN) pathophysiology, in unexplained polycythemia/erythrocytosis (PE) of IgAN patients. METHODS: IgAN-PE patients' serum was collected, analyzed and used to study IgA1 effect on proliferation and differentiation of erythroid progenitors. Hematological parameters of transgenic mice for human alpha1 heavy chain were studied. Multicentric observational cohorts of chronic kidney disease (CKD) patients, including both native kidney diseases and renal transplants, were studied to analyze patient hemoglobin levels. FINDINGS: We retrospectively identified 6 patients with IgAN and unexplained PE. In large CKD cohorts, IgAN was associated with PE in 3.5% of patients (p<0.001 compared to other nephropathies). IgAN was an independent factor associated with higher hemoglobin levels (13.1g/dL vs 12.2 g/dL, p=0.01). During post-transplant anemia, anemia recovery was faster in IgAN patients. Elevated polymeric/monomeric IgA1 ratio as well as high Gd-IgA1 rate were observed in circulating IgA1 of the 6 IgAN-PE patients as compared with control or IgAN patients without PE. IgA1 from these patients increased the sensitivity of erythroid progenitors to Epo. In mice, we also observed an elevation of hematocrit in alpha1 knock-in mice compared to wild type controls. INTERPRETATION: These data identify a new etiology of erythrocytosis and demonstrate the role of pIgA1 in human erythropoiesis. This syndrome of IgA-related erythrocytosis should be investigated in case of unexplained erythrocytosis and renal disease. FUNDING: This work was supported by INSERM (French national institute for health and medical research), Labex GRex and Imagine Institute (Paris, France).

Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT. Thirty-two SCD patients were evaluated before and on long-term follow-up after HSCT. Overall survival was 94% with no severe (grade III-IV) graft-vs-host disease and a 22% rejection rate (graft failure). Hematological parameters, reticulocyte counts, and levels of lactate dehydrogenase (LDH), endothelin-1 and VCAM-1 normalized in SCD patients post-HSCT. Expression of adhesion molecules on reticulocytes and RBC was lower in patients with sustained engraftment. Levels of IL-18, IL-15 and LDH were higher in patients that developed graft failure. Increased levels of plasma pro-inflammatory cytokines, mainly TNF-α, were found in SCD patients long-term after transplantation. SCD patients with sustained engraftment after allo-HSCT showed decreased reticulocyte counts and adhesiveness, diminished hemolysis, and lower levels of vascular tonus markers. Nevertheless, systemic inflammation persists for at least five years after transplantation, indicating that allo-HSCT does not equally affect all aspects of SCD pathophysiology.

Iron-loaded transferrin potentiates erythropoietin effects on erythroblast proliferation and survival: a novel role through transferrin receptors.

Red blood cell production, or erythropoiesis, is a proliferative process that requires tight regulation. Erythropoietin (Epo) is a glycoprotein cytokine that plays a major role in erythropoiesis by triggering erythroid progenitors/precursors of varying sensitivity. The concentration of Epo in bone marrow is hypothesized to be suboptimal, and the survival of erythroid cells has been suggested to depend on Epo sensitivity. However, the key factors that control Epo sensitivity remain unknown. Two types of transferrin receptors (TfRs), TfR1 and TfR2, are known to play a role in iron uptake in erythroid cells. Here, we hypothesized that TfRs may additionally modulate Epo sensitivity during erythropoiesis by modulating Epo receptor (EpoR) signaling. Using an Epo-sensitive UT-7 (UT7/Epo) erythroid cell and human erythroid progenitor cell models, we report that iron-loaded transferrin, that is, holo-transferrin (holo-Tf), synergizes with suboptimal Epo levels to improve erythroid cell survival, proliferation, and differentiation. This is accomplished via the major signaling pathways of erythropoiesis, which include signal transducer and activator of transcription 5 (STAT5), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), and phosphoinositide-3-kinase (PI3K)/AKT. Furthermore, we found that this cooperation is improved by, but does not require, the internalization of TfR1. Interestingly, we observed that loss of TfR2 stabilizes EpoR levels and abolishes the beneficial effects of holo-Tf. Overall, these data reveal novel signaling properties of TfRs, which involve the regulation of erythropoiesis through EpoR signaling.

Orofacial evaluation of individuals with temporomandibular disorder after LED therapy associated or not of occlusal splint: a randomized double-blind controlled clinical study.

This study compared the effects of LED therapy associated with occlusal splint (OS) on the signs and symptoms of temporomandibular disorder (TMD). In this randomized, double-blind clinical trial, 70 TMD patients were randomly divided into six groups. The volunteers received the following treatments: Group 1 (G1) was the control and received only conventional therapy with OS; Group 2 (G2) was the placebo and received treatment with OS and therapy with LED (device turned off); Group 3 (G3) LED therapy (infrared,) once a week; Group 4 (G4) LED therapy (infrared) twice a week; Group 5 (G5) OS associated with LED (infrared) therapy (once a week); Group 6 (G6) received OS therapy plus infrared LED (two sessions per week). The patients were evaluated before, after, and 30 days after treatment. The pain intensity in masticatory system was recorded at each interval. The evaluation of the electromyographic signals (EMG) of the muscles (masseter and temporal) and blood lactate was performed before and after treatment. The associated groups presented better clinical results in relation to the control. The associated groups showed significant differences (p < 0.05) from control in the analysis of pain intensity and in decrease of the RMS value (EMG analysis). In the intragroup analysis, the volunteers in G6 exhibited a significant reduction (p < 0.05) in blood lactate. In conclusion, the association of LED therapy and OS presented superior results in relation to the isolated therapies, especially the protocol with two weekly sessions.

Postpartum Polyneuropathy in a Mare: A Case Report.

Obstetric paralysis is a generic term used to describe postpartum locomotor alterations resulting from nerve damage, widely reported in cattle, but rare in equines. The aim of this study is to report a case of a peripheral polyneuropathy in a primiparous mare, 3 years old, of Mangalarga Marchador breed, after a dystocia lasting approximately 12 hours. At the time of delivery, the head of the fetus was exposed in the vulva and there was flexion of the thoracic limbs. These events culminated in a framework of extreme abduction of the pelvic limbs, thus generating functional impotence and leading the animal to adopt a frog anddecubitus position. After three days of treatment with no improvement in the clinical framework, the animal was euthanized. In the postmortem examination, perineural hemorrhagic lesions were observed in the obturator and sciatic nerves, characterizing the diagnosis of obstetric paralysis. It is possible the outcome of the case would have been satisfactory if there had been an early fetotomy or postpartum treatment had been more prolonged; however, these measures depend on the availability of equipment, conditions of care, and consideration of the owner.

Sheep urinary tract architecture is not affected by acute urethral obstruction / A arquitetura do trato urinário de ovinos não é afetada pela obstrução uretral aguda

Urolithiasis affects the urinary tract of small ruminants, thereby requiring the animal to prematurely terminate breeding. Morphometric study of organs can be used as a diagnostic method. Thus, this study aimed to describe the macroscopic, histopathological, and histomorphometric changes in the urinary tract of sheep with urolithiasis. For this purpose, 14 healthy male Santa Inês sheep, approximately 90 days old, were studied and fed an experimental diet. After the development of urolithiasis, the animals were reorganized into two groups, D1 (without urolithiasis) and D2 (with urolithiasis) for comparative data analysis. Sheep were necropsied to evaluate the pathological changes, followed by macroscopic morphometric analysis, and the histopathological and histomorphometric characteristics were described. Urethral necrosis and a full urinary bladder were observed in all animals that developed the disease. The comparison between sheep with and without urolithiasis showed no significant difference (P < 0.05) in the evaluated macroscopic morphometric variables, except for the right ureter width. Regarding the histopathological evaluation, multifocal areas of mild to moderate congestion within the glomerular tufts and protein in the tubular lumen of the kidneys were observed. In the liver, mild to moderate fatty degeneration was noted in the centrolobular regions, and an ulcerated focal area in the bladder mucosa was observed in only one animal. The present study demonstrated that the formulated diet was effective in inducing clinical disease. In acute obstructive urolithiasis in sheep tissue, lesions in the liver and urinary tract were observed, although there were no significant histomorphometric changes.(AU)

Urolitíase acomete o trato urinário de pequenos ruminantes causando a saída prematura de animais destinados à reprodução. O estudo morfométrico dos órgãos pode ser empregado como método de auxílio diagnóstico. Assim, este estudo objetivou descrever as alterações macroscópicas, histopatológicas e histomorfométricas do trato urinário de ovinos com urolitíase. Com esse fim, foram utilizados 14 ovinos hígidos, machos, da raça Santa Inês com idade aproximada de 90 dias, que receberam dieta experimental. Após o desenvolvimento da urolitíase os animais foram reorganizados em dois grupos experimentais distintos D1 (sem urolitíase) e D2 (com urolitíase) para a análise comparada dos dados. Os ovinos foram necropsiados para descrição das alterações patológicas, seguindo-se a análise morfométrica macroscópica e descrição quanto as características histopatológicas e histomorfométricas. Necrose de processo uretral e bexiga urinária repleta foram observados em todos os animais que desenvolveram a doença. Na comparação entre os ovinos com e sem urolitíase não houve diferença significativa (P < 0,05) nas variáveis morfométricas macroscópicas avaliadas, a exceção da largura do ureter direito. Quanto à avaliação histopatológica, foram observadas áreas multifocais de discreta a moderada congestão dos tufos glomerulares e proteína no lúmen tubular nos rins. No fígado, observou-se nas regiões centrolobulares, discreta a moderada degeneração gordurosa e apenas em um animal foi observada, macro e microscopicamente, área focal ulcerada na mucosa da bexiga. Os achados da presente pesquisa demonstraram que a dieta formulada foi eficaz na indução da doença clínica. Na urolitíase obstrutiva aguda em ovinos, lesões teciduais em fígado e trato urinário são observadas, mas não há alterações histomorfométricas significativas.(AU)