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1.
Adv Physiol Educ ; 48(3): 512-517, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38721651

RESUMO

Internationalization in higher education is essential, and although active learning methodologies are increasing and allow students to develop transversal skills, most still have a very local scope. In this context, the Collaborative Online International Learning (COIL) methodology is an interesting approach to benefit the students' development. It consists of an online program that involves creating multicultural teams to develop a specific learning project. Although this methodology is expanding, its use in physiology is still scarce. This paper aims to show an example of applying COIL methodology in physiology topics to enhance higher-education students' innovation and business skills. Our example project developed a sports-assessment service concept focused on physiology and biomechanics assessments. The program involved teams from Brazil, Germany, and Spain, comprising undergraduate and master students. Over 7 weeks, these teams, mentored by professors and researchers, engaged in workshops covering COIL methodology, business model design, executive summary planning, economic analyses, and communication techniques. Key outcomes included learning new concepts, developing soft skills, building confidence in innovative solution proposals, and experiencing diverse cultures. Challenges faced were language barriers, scheduling, task complexity, and logistical issues. This experience confirms the effectiveness of incorporating programs using COIL methodology into educational curriculums. Doing so exposes physiology students to innovation, entrepreneurship, and business creation while strengthening their professional connections and opening up postgraduation opportunities.NEW & NOTEWORTHY Although the Collaborative Online International Learning (COIL) methodology is expanding, its use in physiology is still scarce. Our example COIL project of 7 weeks developed a sports-assessment service concept focused on physiology and biomechanics assessments. The program involved teams from Brazil, Germany, and Spain, comprising undergraduate and master's students. Students perceived extracurricular activities in this format as beneficial. Coaches also expressed positive views about such initiatives, noting benefits for students and their development.


Assuntos
Fisiologia , Humanos , Fisiologia/educação , Educação a Distância/métodos , Internacionalidade , Currículo , Comportamento Cooperativo
2.
Sensors (Basel) ; 23(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37765752

RESUMO

Non-specific low back pain (NSLBP) is a highly prevalent condition that implies substantial expenses and affects quality of life in terms of occupational and recreational activities, physical and psychological health, and general well-being. The diagnosis and treatment are challenging processes due to the unknown underlying causes of the condition. Recently, sensors have been included in clinical practice to implement its management. In this review, we furthered knowledge about the potential benefits of sensors such as force platforms, video systems, electromyography, or inertial measure systems in the assessment process of NSLBP. We concluded that sensors could identify specific characteristics of this population like impaired range of movement, decreased stability, or disturbed back muscular activation. Sensors could provide sufferers with earlier diagnosis, prevention strategies to avoid chronic transition, and more efficient treatment approaches. Nevertheless, the review has limitations that need to be considered in the interpretation of results.


Assuntos
Dor Lombar , Humanos , Dor Lombar/diagnóstico , Dor Lombar/terapia , Qualidade de Vida , Medição da Dor
3.
J Therm Biol ; 110: 103345, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36462854

RESUMO

Infrared thermography (IRT) has become popular in several areas of knowledge. However, the analyses of thermal images often request manual actions, and little is known about the effect of the evaluator's experience on analysis thermal images. Here, we determine the reproducibility of IRT images analysis performed by evaluators with different levels of experience. Eight evaluators (GE, group experienced, n = 4; GN, group novice, n = 4) analyzed thermograms from 40 healthy participants recorded before and after exercise to determine the mean, minimum, maximum, standard deviation, and range of skin temperature in the anterior thigh and posterior leg. Before and after exercise, mean temperature showed excellent reproducibility for both groups for the anterior thigh (ICC >0.98) and posterior leg (ICC >0.94), and maximum temperature showed excellent reproducibility for both groups in the posterior leg (ICC >0.91). The influence of experience level was not significant considering the anterior thigh. Similarly, experience level did not affect the mean, maximum, and standard deviation temperature determined for the posterior leg. For the posterior leg, minimum temperature presented lower values and the range was higher among novice evaluators. Mean skin temperature showed narrower 95% limits of agreement than minimum and maximum for both regions and moments. Caution is advised when temperature ranges and minimums are determined by different evaluators. We conclude that for IRT analysis by evaluators with different levels of experience, the mean and maximum temperatures should be prioritized due to their better reproducibility.


Assuntos
Temperatura Cutânea , Termografia , Humanos , Reprodutibilidade dos Testes , Processamento de Imagem Assistida por Computador , Exercício Físico
4.
Int J Mol Sci ; 23(3)2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35163323

RESUMO

The chemokine receptor CCR7 and its ligands CCL19 and CCL21 regulate the lymph node homing of dendritic cells and naïve T-cells and the following induction of a motile DC-T cell priming state. Although CCL19 and CCL21 bind CCR7 with similar affinities, CCL21 is a weak agonist compared to CCL19. Using a chimeric chemokine, CCL19CCL21N-term|C-term, harboring the N-terminus and the C-terminus of CCL21 attached to the core domain of CCL19, we show that these parts of CCL21 act in a synergistic manner to lower ligand potency and determine the way CCL21 engages with CCR7. We have published that a naturally occurring basic C-terminal fragment of CCL21 (C21TP) boosts the signaling of both CCL19 and CCL21. Boosting occurs as a direct consequence of C21TP binding to the CCR7 N-terminus, which seems to free chemokines with basic C-termini from an unfavorable interaction with negatively charged posttranslational modifications in CCR7. Here, we confirm this using a CCL19-variant lacking the basic C-terminus. This variant displays a 22-fold higher potency at CCR7 compared to WT CCL19 and is highly unaffected by the presence of C21TP. WT CCL19 has a short basic C-terminus, CCL21 a longer one. Here, we propose a way to differentially boost CCL19 and CCL21 activity as short and long versions of C21TP boost CCL19 activity, whereas only a long C21TP version can boost chemokines with a full-length CCL21 C-terminus.


Assuntos
Quimiocina CCL19 , Quimiocina CCL21 , Peptídeos , Receptores CCR7 , Quimiocina CCL19/metabolismo , Quimiocina CCL21/metabolismo , Ligantes , Peptídeos/metabolismo , Peptídeos/farmacologia , Receptores CCR7/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo
5.
J Therm Biol ; 98: 102926, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34016349

RESUMO

During the transition between warm-up and competition there is a change in core, muscle and (eventually) skin temperature that may affect swimming performance. We have aimed to assess skin temperature evolution during transition phases of different durations before a typical front crawl effort and to investigate its relationship with performance. Following a standardized warm-up, nine adolescent male swimmers performed three maximal randomized 100 m maximum front crawl trials after 10, 20 and 45 min transition phases. Skin temperature, performance (time, stroke frequency, length and index, and propelling efficiency), heart rate, lactate and perceived effort were assessed. Data showed a skin temperature log increase over time (R2 > 0.96, p < 0.01) without differences from the 15 min with the following instants. Performance and psychophysiological variables were similar between transition phases. However, skin temperature at the end of the transition periods, i.e., just before the 100 m trials, was lower in the 10 min than the 20 and 45 min transitions (32.0 ± 0.6 vs 33.0 ± 0.4 and 33.5 ± 0.5 °C, respectively). The main finding was that no relevant relationships were observed between pre-test skin temperature and performance times (|r| < 0.6, p > 0.05) for the studied transition phases. We have concluded that transitions longer than 10 min will not present thermal changes and that, within the physiologic limits studied, pre-exercise skin temperature does not influence swimming performance.


Assuntos
Desempenho Atlético , Temperatura Cutânea , Natação/fisiologia , Exercício de Aquecimento/fisiologia , Adolescente , Humanos , Masculino
6.
J Therm Biol ; 101: 103098, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34879916

RESUMO

Although dynamic thermography skin temperature assessment has been used in medical field, scientific evidence in sports is scarce. The aim of the study was to assess changes in anterior thigh skin temperature in response to a cold stress test after a strength exercise fatiguing protocol. Ten physically active adults performed a familiarization session and two strength exercise sessions, one with dominant and the other with non-dominant lower limb. Participants performed bouts of 10 concentric and eccentric contractions of leg extensions in an isokinetic device until reaching around 30% of force loss. Infrared thermographic images were taken at baseline conditions and after the fatigue level from both thighs after being cooled using a cryotherapy system. ROIs included vastus medialis, rectus femoris, adductor and vastus lateralis. Skin temperature rewarming was assessed during 180s after the cooling process obtaining the coefficients of the following equation: ΔSkin temperature = ß0 + ß1 * ln(T), being ß0 and ß1 the constant and slope coefficients, respectively, T the time elapsed following the cold stress in seconds, and ΔSkin temperature the difference between the skin temperature at T respect and the pre-cooling moment. Lower ß0 and higher ß1 were found for vastus lateralis and rectus femoris in the intervention lower limb compared with baseline conditions (p < 0.05 and ES > 0.6). Adductor only showed differences in ß0 (p = 0.01 and ES = 0.92). The regressions models obtained showed that ß0 and ß1 had a direct relationship with age and muscle mass, but an inverse relationship with the number of series performed until 30% of fatigue (R2 = 0.8). In conclusion, fatigue strength exercise results in a lower skin temperature and a faster thermal increase after a cold stress test.


Assuntos
Resposta ao Choque Frio , Exercício Físico/fisiologia , Fadiga/fisiopatologia , Temperatura Cutânea , Coxa da Perna/fisiologia , Adulto , Feminino , Humanos , Masculino , Termografia , Adulto Jovem
7.
J Therm Biol ; 98: 102913, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34016340

RESUMO

Infrared thermography (IRT) has been gaining in popularity in clinical and scientific research due to the increasing availability of affordable infrared cameras. This study aims to determine the similarity of measurement performance between three models of IRT camera during assessment of skin temperature before and after physical exercise. Three models of FLIR thermographic cameras (E60bx, Flir-One Pro LT, and C2) were tested. Thermal images were taken of the foot sole, anterior leg, and anterior thigh from 12 well-trained men, before and after a 30-min run on a treadmill. Image files were blinded and processed by three evaluators to extract the mean, maximum, and standard deviation of skin temperature of the region of interest. Time for data processing and rate of perceived effort was also recorded. Data processing was slower on the E60bx (CI95% E60 vs C2 [0.2, 2.6 min], p = 0.02 and ES = 0.6); vs. Flir-One [0.0, 3.4 min], p = 0.03 and ES = 0.6) and was associated with lower effort perception (E60 3.0 ± 0.1 vs. Flir-One 5.6 ± 0.2 vs C2 7.0 ± 0.2 points; p < 0.001 and ES > 0.8). The C2 and Flir-One cameras underestimated the temperature compared with the E60. In general, measuring mean temperature provided higher camera and examiner intra-class correlations than maximum and standard deviation, especially before exercise. Moreover, post exercise mean skin temperatures provided the most consistent values across cameras and evaluators. We recommend the use of mean temperature and caution when using more than one camera model in a study.


Assuntos
Raios Infravermelhos , Corrida/fisiologia , Temperatura Cutânea , Termografia/instrumentação , Adolescente , Adulto , , Humanos , Perna (Membro) , Masculino , Adulto Jovem
8.
J Therm Biol ; 92: 102639, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32888554

RESUMO

The aim of the study was to evaluate an automatic thermographic software package (ThermoHuman®) for assessing skin temperature on the soles of the feet before and after running and to compare it with two manual definitions of the regions of interest (ROIs). 120 thermal images of the soles of the feet of 30 participants, at two measurement points (before and after running 30 min) and on two measurement days were analyzed. Three different models of thermographic image analyses were used to obtain the mean temperature of 9 ROIs: A) ThermoHuman (automatic definition of ROIs using ThermoHuman® software), B) Manual (manual delimitation of ROIs by proportion criteria), and C) Manual-TH (manual delimitation of ROIs in an attempt to replicate the regions analyzed by ThermoHuman). ThermoHuman resulted in an 86% reduction in time involved compared to manual delimitation. Fourteen of the 120 images (12%) presented some error in one or more of the ROI delimitations. Although the three procedures presented significant differences between them (53% in the comparison between ThermoHuman and Manual, 47% between ThermoHuman and Manual-TH, and 28% between Manual and Manual-TH), all differences had a small effect size (ES 0.2-0.4) or lower (ES < 0.2). Bland-Altman plots showed similar 95% limits of agreement between the three procedures before and after running. Intraclass correlation coefficient analysis of the three procedures presented excellent reliability (ICC>0.8). In conclusion, ThermoHuman® software was observed to be time-saving for image analysis with excellent reliability. Although results suggest that ThermoHuman® and manual methods are both valid in themselves, combining them is not recommended due to the differences observed between them.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Temperatura Cutânea , Validação de Programas de Computador , Termografia/métodos , Adulto , Feminino , Pé/fisiologia , Humanos , Masculino , Corrida , Software , Adulto Jovem
9.
J Therm Biol ; 91: 102612, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32716862

RESUMO

There is a lack of evidence about the effect of different type of foot orthoses on plantar surface temperature. Moreover, that effect could be different depending on gender due to anatomical and physiological differences between men and women. The aim of the study was to analyze the effect of a prefabricated thermoformable foot orthosis on plantar surface temperature after running and taking gender differences into account. Thirty recreational runners (15 males, mean (standard deviation): 28 (7) years, 69.7 (6.5) kg, 1.74 (0.05) cm and 22.9 (1.7) kg/m2; and 15 females: 35 (7) years, 55.2 (6.9) kg, 1.63 (0.06) cm and 20.6 (1.9) kg/m2) carried out a maximum incremental test as pre-test, and two running tests on a treadmill at the laboratory wearing previously randomized different foot orthoses (thermoformable and prefabricated generic). The plantar surface temperature of the dominant foot sole in ten regions of interest was assessed before and immediately after 30-min running at 75% of VO2max. The use of thermoformable foot orthoses produced lower temperatures only in men after the run in medial heel (P = 0.033, ES = 0.7), which then disappeared in temperature variation (after - before) (P = 0.910). Regarding gender, women showed lower temperatures before the run in both orthosis conditions (P < 0.039, ES > 0.8), but no differences in temperatures after the run (P = 0.910) in comparison with men. Moreover, absolute temperatures after running were always greater than before the run (P < 0.001, ES > 5.0). In conclusion, the thermoformable foot orthoses do not modify plantar surface temperature after running in healthy runners of either gender, compared to prefabricated generic foot orthoses. Although women present lower baseline plantar temperatures than men, these differences disappear after exercise.


Assuntos
Órtoses do Pé/efeitos adversos , Pé/fisiologia , Corrida/fisiologia , Sapatos/efeitos adversos , Temperatura Cutânea , Adulto , Feminino , Órtoses do Pé/normas , Humanos , Masculino , Distribuição Aleatória , Fatores Sexuais , Sapatos/normas
10.
J Therm Biol ; 91: 102613, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32716863

RESUMO

The aim of the study was to evaluate skin temperature of the soles of the feet before and after a provoked asymmetrical running. Seventeen recreational male runners performed two 15 min running tests in the same session. In the first test, participants performed running without modifying their running technique (control condition). In the second running test, they repeated the same protocol using an ankle weight of 1.5 kg in the non-dominant ankle (asymmetrical condition). Rate of perceive exertion, heart rate and spatio-temporal parameters were measured during the running tests. Skin temperature was measured with an infrared camera before and after each condition. Generally, comparing both lower limbs, non-preferred limb (with the ankle weight) had lower contact time (p < 0.001 and ES > 0.8), higher stride length (p < 0.05 and ES > 0.3) and higher stride frequency in asymmetrical condition (p < 0.01 and ES > 0.4). However, no differences were observed on skin temperature between both feet in the two conditions in any of the regions of interest assessed (p > 0.05). Although the asymmetry generation model used provoked technical asymmetries in spatio-temporal parameters during running, no thermal asymmetries were observed between preferred and non-preferred sole of the foot. These results suggested the lower importance of mechanical than physiological mechanisms on skin temperature during running.


Assuntos
Pé/fisiologia , Corrida/fisiologia , Temperatura Cutânea , Adulto , Tornozelo/fisiologia , Fenômenos Biomecânicos , Peso Corporal , Humanos , Masculino
12.
Appl Opt ; 56(19): 5559-5565, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29047517

RESUMO

The main instruments to assess foot eversion have some limitations (especially for field applications), and therefore it is necessary to explore new methods. The objective was to determine the relationship between foot eversion and skin temperature asymmetry of the foot sole (difference between medial and lateral side), using infrared thermography. Twenty-two runners performed a running test lasting 30 min. Skin temperature of the feet soles was measured by infrared thermography before and after running. Foot eversion during running was measured by kinematic analysis. Immediately after running, weak negative correlations were observed between thermal symmetry of the rearfoot and eversion at contact time, and between thermal symmetry of the entire plantar surface of the foot and maximum eversion during stance phase (r=-0.3 and p=0.04 in both cases). Regarding temperature variations, weak correlations were also observed (r=0.4 and p<0.05). The weak correlations observed in this study suggest that skin temperature is not related to foot eversion. However, these results open interesting future lines of research.


Assuntos
Pé/fisiologia , Pronação/fisiologia , Corrida/fisiologia , Temperatura Cutânea/fisiologia , Termografia/métodos , Adulto , Feminino , Humanos , Masculino , Fatores de Tempo
13.
Nature ; 467(7313): 318-22, 2010 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-20844535

RESUMO

The ß-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of ß-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound ß(E)/ß(0)-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas. The ß(E)-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated ß(E)-globin with partial instability. When this is compounded with a non-functional ß(0) allele, a profound decrease in ß-globin synthesis results, and approximately half of ß(E)/ß(0)-thalassaemia patients are transfusion-dependent. The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral ß-globin gene transfer, an adult patient with severe ß(E)/ß(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl(-1), of which one-third contains vector-encoded ß-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.


Assuntos
Transfusão de Sangue , Terapia Genética , Proteína HMGA2/metabolismo , Globinas beta/genética , Globinas beta/metabolismo , Talassemia beta/genética , Talassemia beta/terapia , Adolescente , Células Sanguíneas/citologia , Células Sanguíneas/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Pré-Escolar , Células Clonais/metabolismo , Expressão Gênica , Vetores Genéticos/genética , Proteína HMGA2/genética , Homeostase , Humanos , Lentivirus/genética , Masculino , MicroRNAs/genética , Especificidade de Órgãos , RNA Mensageiro/análise , RNA Mensageiro/genética , Fatores de Tempo , Ativação Transcricional , Adulto Jovem , Talassemia beta/metabolismo
14.
Blood ; 121(9): 1510-6, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23264593

RESUMO

On the basis of a nationwide database of 160 patients with Wiskott-Aldrich syndrome (WAS), we identified a subset of infants who were significantly more likely to be attributed with an Ochs score of 5 before the age of 2 (n = 26 of 47 [55%], P = 2.8 × 10(−7)). A retrospective analysis revealed that these patients often had severe refractory thrombocytopenia (n = 13), autoimmune hemolytic anemia (n = 15), and vasculitis (n = 6). One patient had developed 2 distinct cancers. Hemizygous mutations predictive of the absence of WAS protein were identified in 19 of the 24 tested patients, and the absence of WAS protein was confirmed in all 10 investigated cases. Allogeneic hematopoietic stem cell transplantation (HSCT) was found to be a curative treatment with a relatively good prognosis because it was successful in 17 of 22 patients. Nevertheless, 3 patients experienced significant disease sequelae and 4 patients died before HSCT. Therefore, the present study identifies a distinct subgroup of WAS patients with early-onset, life-threatening manifestations. We suggest that HSCT is a curative strategy in this subgroup of patients and should be performed as early in life as possible, even when a fully matched donor is lacking.


Assuntos
Síndrome de Wiskott-Aldrich/diagnóstico , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Prognóstico , Projetos de Pesquisa , Índice de Gravidade de Doença , Síndrome de Wiskott-Aldrich/epidemiologia , Síndrome de Wiskott-Aldrich/patologia , Adulto Jovem
15.
Blood ; 121(19): 3981-7, 2013 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-23493783

RESUMO

We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P = .031) and HLA-mismatched UD (41%; P = .007). Full-donor chimerism (P = .039) and normal enzyme levels (P = .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Mucopolissacaridose I/terapia , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Mucopolissacaridose I/epidemiologia , Mucopolissacaridose I/mortalidade , Agonistas Mieloablativos/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Condicionamento Pré-Transplante/efeitos adversos , Resultado do Tratamento , Adulto Jovem
16.
Nat Rev Immunol ; 2(8): 615-21, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12154380

RESUMO

The concept that the outcome of a devastating disease can be modified by inserting a transgene into abnormal cells is appealing. However, the gene-transfer technologies that are available at present have limited the success of gene therapy so far. Nevertheless, severe combined immunodeficiencies are a useful model, because gene transfer can confer a selective advantage to transduced cells. In this way, a proof of concept for gene therapy has been provided.


Assuntos
Terapia Genética , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Adenosina Desaminase/genética , Animais , Grupo dos Citocromos b/genética , Humanos , Imunodeficiência Combinada Severa/imunologia , Linfócitos T
17.
Blood ; 120(10): 2144-54, 2012 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-22730537

RESUMO

Invariant natural killer T (iNKT) cells can experimentally dissociate GVL from graft-versus-host-disease (GVHD). Their role in human conventional allogeneic hematopoietic stem cell transplantation (HSCT) is unknown. Here, we analyzed the post-HSCT recovery of iNKT cells in 71 adult allografted patients. Results were compared with conventional T- and NK-cell recovery and correlated to the occurrence of GVHD, relapse, and survival. We observed that posttransplantation iNKT cells, likely of donor origin, recovered independently of T and NK cells in the first 90 days after HSCT and reached greater levels in recipient younger than 45 years (P = .003) and after a reduced-intensity conditioning regimen (P = .03). Low posttransplantation iNKT/T ratios (ie, < 10(-3)) were an independent factor associated with the occurrence of acute GVHD (aGVHD; P = .001). Inversely, reaching iNKT/T ratios > 10(-3) before day 90 was associated with reduced nonrelapse mortality (P = .009) without increased risk of relapse and appeared as an independent predictive factor of an improved overall survival (P = .028). Furthermore, an iNKT/T ratio on day 15 > 0.58 × 10(-3) was associated with a 94% risk reduction of aGVHD. These findings provide a proof of concept that early postallogeneic HSCT iNKT cell recovery can predict the occurrence of aGVHD and an improved overall survival.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Células T Matadoras Naturais/imunologia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Fatores Etários , Feminino , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Efeito Enxerto vs Leucemia/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/patologia , Recidiva , Fatores de Risco , Análise de Sobrevida , Linfócitos T/imunologia , Linfócitos T/patologia , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo
18.
Blood ; 119(12): 2949-55, 2012 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-22308292

RESUMO

Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome. Median follow-up time was 83 months and 58 months for UCBT and MMRDT, respectively. Most UCB recipients received a myeloablative conditioning regimen; most MMRDT recipients did not. UCB recipients presented a higher frequency of complete donor chimerism (P = .04) and faster total lymphocyte count recovery (P = .04) without any statistically significance with the preparative regimen they received. The MMRDT and UCBT groups did not differ in terms of T-cell engraftment, CD4(+) and CD3(+) cell recoveries, while Ig replacement therapy was discontinued sooner after UCBT (adjusted P = .02). There was a trend toward a greater incidence of grades II-IV acute GVHD (P = .06) and more chronic GVHD (P = .03) after UCBT. The estimated 5-year overall survival rates were 62% ± 4% after MMRDT and 57% ± 6% after UCBT. For children with SCID and no HLA-identical sibling donor, both UCBT and MMRDT represent available HSC sources for transplantation with quite similar outcomes.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/cirurgia , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histocompatibilidade , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Imunodeficiência Combinada Severa/mortalidade , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento
19.
Blood ; 120(17): 3615-24; quiz 3626, 2012 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-22791287

RESUMO

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/tratamento farmacológico , Condicionamento Pré-Transplante , Adenosina Desaminase/deficiência , Adenosina Desaminase/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade , Agamaglobulinemia/patologia , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Imunidade Celular , Imunidade Humoral , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Agonistas Mieloablativos/uso terapêutico , Estudos Retrospectivos , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/patologia , Irmãos , Linfócitos T/imunologia , Resultado do Tratamento , Doadores não Relacionados
20.
Geriatrics (Basel) ; 9(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38667510

RESUMO

The 2-minutes walking test (2-MWT) is a valid and reliable test that has a high correlation with the distance walked in the 6-minutes walking test (6-MWT). However, to date, no study has determined the relationship between 2-MWT performance and the aerobic fitness indices obtained during a maximal incremental test to confirm if this test is a valid surrogate of aerobic fitness in apparently healthy older adults. The main objective of this work was to identify the factors associated to the performance in the 2-MWT, including aerobic fitness, functional and spatial-temporal gait parameters. Seventeen elderly adults performed a maximal incremental cycling test to determine maximum oxygen consumption (VO2max) and ventilatory thresholds (VT1 and VT2), two static standing balance tests with open and close eyes, a 5-times sit-to-stand test (5-TSTS), a handgrip test, and a 2-MWT on three different days over 2 weeks. No correlations were found between aerobic fitness indices and the distance covered in 2-MWT, but significant moderate correlations were found between the distance covered in 2-MWT and the time to perform the 5-TSTS (rho = -0.49) and with stride length (rho = 0.52) during the test. In conclusion, the 2-MWT does not seem a good test to assess aerobic capacity while it showed to be associated to the 5-TSTS performance of the elderly.

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