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ECA2, Infeccao por SARS-CoV-2 e Envelhecimento Alteracoes induzidas pelo envelhecimento em vias metabolicas podem, em parte, explicar a maior taxa de morbimortalidade por COVID-19 em pacientes idosos. Dentre estas, destacam-se aquelas pertencentes ao sistema renina-angiotensina (SRA), haja vista o papel crucial que esse sistema desempenha tanto na transmissibilidade viral como na patogenia da lesao pulmonar aguda e de sua forma mais grave, a sindrome da angustia respiratoria aguda (SARA). Sabe-se que a ECA2 age como um receptor para a proteina [...]

Objectives The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). Methods We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). Results After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). Conclusion Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.

In this study we produced antigenic extracts from prototypical strains of C. neoformans (VNI-VNIV) and C. gattii (VGI-VGIV) and tested IFN-γ secretion by Elispot. Antigens from the eight Cryptococcus molecular types (VNI -VNIV and VGI - VGIV) were obtained after capsule reduction. IFN-γ secretion by Elispot method were stimulated with C. neoformans and C. gattii antigens. Peripheral blood mononuclear cells of fourteen healthy control subjects, being: five ecotourists, two mycologists, three poultry keepers, and four individuals without reports of exposure to the fungus. We observed a significant increase in IFN-γ secretion in the group of ecotourists, mycologists and bird keepers in relation to the group of individuals without reports of occupational exposures to these agents. Our results suggest the significant increase in IFN-γ secretion may be related to the continuous exposure of these groups of individuals to the fungus, as well as to the specific antigen memory immune response developed during exposure to Cryptococcus.

This study evaluated changes in the bacterial community in high-moisture and rehydrated corn grain silage, and their correlation with fermentation quality attributes in distinct corn hybrids, the storage period, and kernel maturity at plant harvest. Most silages achieved good fermentation (pH

Immunosenescence are alterations on immune system that occurs throughout an individual life. The main characteristic of this process is replicative senescence, evaluated by telomere shortening. Several factors implicate on telomere shortening, such as smoking. In this study, we evaluated the influence of smoking and Chronic Obstructive Pulmonary Disease (COPD) on cytokines, telomere length and telomerase activity. Blood samples were collected from subjects aged over 60 years old: Healthy (never smokers), Smokers (smoking for over 30 years) and COPDs (ex-smokers for ≥15 years). A young group was included as control. PBMCs were cultured for assessment of telomerase activity using RT-PCR, and cytokines secretion flow cytometry. CD4+ and CD8+ purified lymphocytes were used to assess telomere length using FlowFISH. We observed that COPD patients have accelerated telomere shortening. Paradoxically, smokers without lung damage showed preserved telomere length, suggesting that tobacco smoking may affect regulatory mechanisms, such as telomerase. Telomerase activity showed diminished activity in COPDs, while Smokers showed increased activity compared to COPDs and Healthy groups. Extracellular environment reflected this unbalance, indicated by an anti-inflammatory profile in Smokers, while COPDs showed an inflammatory prone profile. Further studies focusing on telomeric maintenance may unveil mechanisms that are associated with cancer under long-term smoking.

The ensiling process, as well as the hybrid type and moisture content of corn grains, can affect the fermentation profile and nutrient digestibility of grain silages. Therefore, this study evaluated the effects of hybrid type, grain moisture content at harvest, and length of storage on the fermentation profile, DM digestibility (DMD), and starch digestibility (StarchD) of corn grain silages. We evaluated corn grains harvested at three moisture contents: at approximately 500 g/kg DM (500DM); high-moisture corn at approximately 700 g/kg DM (HMC); and dry grain at approximately 800 g/kg DM, reconstituted to approximately 700 g/kg DM (RC). At RC and HMC, the flint hybrid had an average of 24 % higher (P

Os estágios avançados da DPOC são longos e dolorosos processos onde há o aumento dos sintomas, fazendo com que o paciente entre em um ciclo vicioso de deterioração da capacidade física, dispneia, ansiedade e isolamento social. Deste modo, o exercício vem se mostrando um componente importante na DPOC, auxiliando no tratamento medicamentoso para a redução dos sintomas e melhora da qualidade de vida. Neste contexto, não há muitos relatos na literatura sobre o papel da atividade física no padrão de secreção de citocinas e na resposta proliferativa de pacientes com DPOC. Além disso, não há muita concordância sobre o comprimento do telômero e fenótipo celular quando a comparados tabagistas que não desenvolvem a doença e pacientes com DPOC. O objetivo deste trabalho foi comparar alguns parâmetros imunológicos entre pacientes com DPOC e indivíduos tabagistas sem DPOC, e em pacientes com DPOC antes e após o programa de reabilitação oferecido no Hospital das Clínicas da FMUSP. As coletas de sangue foram realizadas em dois momentos para o grupo DPOC (pré e pós-programa de reabilitação pulmonar), e em um único momento para o grupo tabagista. Estas amostras foram processadas para obtenção de células mononucleares do sangue periférico, onde foram analisados os seguintes parâmetros: proliferação celular e apoptose, fenotipagem de linfócitos, comprimento relativo do telômero e dosagem de citocinas. Verificamos que indivíduos tabagistas possuem menores quantidades de proteína C reativa que pacientes com DPOC, e uma tendência a maior número de linfócitos. Além disso, o comprimento relativo do telômero em tabagistas é maior do que em pacientes com DPOC, especialmente em linfócitos TCD8+, e em menor grau em linfócitos TCD4+. Linfócitos TCD8+ de portadores de DPOC apresentaram maiores porcentagens de células terminalmente diferenciadas, sugerindo exaustão celular destes linfócitos, e menores porcentagens de células de memória central e memória efetora. Pacientes com DPOC apresentam maiores quantidades de citocinas comparados aos tabagistas sem DPOC. Já na comparação pré e pós-reabilitação verificamos menores quantidades de leucócitos, menores pontuações nos questionários de sintomas, e maiores distâncias percorridas no teste de caminhada de 6 minutos. Na avaliação da linfoproliferação, para as células estimuladas com mitógeno (fitohemaglutinina) e antígenos (citomegalovirus e Haemophilus influenza) foi possível verificar melhora na resposta linfoproliferativa dos pacientes no período pós-reabilitação, assim como maiores níveis da citocina imunoreguladora IL-10. Deste modo concluímos que pacientes com DPOC possuem um perfil mais pró-inflamatório e de diferenciação terminal que tabagistas sem a doença e que exercício físico é capaz de modular o ambiente inflamatório melhorando alguns parâmetros da resposta imune celular The advanced stages of COPD are long and painful with increase of symptoms making the patients enter a vicious cycle of deterioration of physical capacity, dyspnea, anxiety and social isolation. Therefore, the exercise shows an important component of COPD pathogenesis, assisting in pharmacological treatment, reducing symptoms and enhancing life quality. In this context, there are no concise reports in literature about the role of physical activity in the pattern of cytokine secretion and proliferative response in COPD patients. Besides this, there is no consensus in the data comparing smokers with COPD and smokers without COPD. Because of this, we compared some immune parameters of smokers with COPD and smokers without COPD, and evaluated the cellular immune response before and after a rehabilitation program offered at the Hospital das Clínicas FMUSP. Blood collection was performed in two moments in the COPD group (before and after the rehabilitation program), and once in smokers without COPD. After that the samples were processed to peripheral blood mononuclear cells isolation, in which were analyzed the cellular proliferation and apoptosis, the lymphocyte phenotypic characteristics, the telomere length and the cytokines levels in serum and culture supernatants. Smokers without COPD have lower levels of C reactive protein, and a trend to greater percentages of lymphocytes than in smoker with COPD. The telomere length of COPD patients was shorter than that of smokers without COPD, especially in TCD8+ lymphocytes, with a non-significant trend in the TCD4+ lymphocytes. The TCD8+ subpopulation of COPD patients comprised greater percentages of terminally differentiated cells, and lower percentages of central memory and effector memory cells, suggesting a bias to more terminally differentiated (and eventually exhausted) cells. Moreover, the levels of pro inflammatory cytokines were greater in COPD patients. Evaluation of the exercise effect, we found greater quantities of leucocytes, lower scores in the symptoms questionnaires and longer distances in the six minute walk test after the rehabilitation program. Besides this, the proliferative response to the mitogen phytohemaglutinin, and the antigens from cytomegalovirus and nontypeable Haemophilus influenza were all improved after the exercise program with greater levels of secretion of the anti-inflammatory cytokine IL-10. In conclusion, COPD patients have a pro inflammatory profile and a bias for more terminally differentiated (and eventually exhausted) cells when compared with smokers without COPD, and that the exercise program is capable of modulating the inflammatory microenvironment enhancing some parameters of the cellular immune response

Exercise training has been shown to reduce symptoms and exacerbations in COPD patients; however, the exercise effect on patients’ immune response is poorly known. We thus verified if an exercise program (EP) impacted on proliferative T cell response of COPD patients. Fourteen non-O2 dependent COPD patients on standard treatment were studied. EP consisted in 24 sessions of aerobic and muscular training. Peripheral blood mononuclear cells were stimulated with the mitogen phytohemagglutinin and antigens from Haemophilus influenzae and cytomegalovirus, and the lymphocyte proliferative response (LPR) was assessed through the expression of Ki67 before and after the EP. The Quality of life [COPD assessment test (CAT)], dyspnea [(modified Medical Research Council scale (mMRC)], and 6-min walk distance were also assessed. The EP program increased significantly the LPR of TCD4+ lymphocytes to phytohemagglutinin and cytomegalovirus and H. influenzae antigens, but with TCD8+ lymphocytes the increase was less marked. Consistent with this, a higher proportion of TCD8+ than TCD4+ cells did not express the costimulatory molecule CD28. The EP also resulted in improvement of the quality of life, dyspnea, and physical capacity. The improvement in TCD4+ cell function may represent an additional mechanism through which the EP results in less exacerbations and hospitalizations.

The importance of the recurrent laryngeal nerve in surgery on the anterior region of the neck has motivated many published papers on critical points of its pathway, relationship with the inferior thyroid artery, penetration in the larynx, division outside the larynx, and branches communicating with the internal branch of the superior laryngeal nerve. We analyze the terminal branches of the recurrent laryngeal nerve and their distribution through the laryngeal muscles. 44 laryngeal nerves had been dissected. Most frequently, the recurrent laryngeal nerve presents a division below or at the level of the lower margin of the cricoid cartilage (outside the larynx). One of these branches forms the communication with the internal branch of the superior laryngeal nerve, and the other penetrates the laryngeal space. Above the lower margin of the cricoid cartilage, the inferior laryngeal nerve issues a variable number of branches to muscles (3 to 7): to the posterior cricoarytenoid muscle; to the oblique and transversal arytenoid muscles; and to the lateral cricoarytenoid muscle and the thyroarytenoid muscle.

Background: Fanconi anemia (FA) is the most frequent genetic cause of bone marrow failure (BMF) due to a DNA repair mechanism defect. The natural history of FA is marked by progressive BMF during early childhood. Throughout life, the hematopoietic situation may change by clonal evolution toward myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure in FA patients. The role of HSCT for FA patients with AML or advanced MDS is less defined. Currently, HSCT first line result offers 50% Overall Survival (OS) for patients with cytogenetic abnormalities only and 30% OS for patients with advanced MDS or AML in FA (Ayas et al., JCO 2013; Mitchell et al., BJH 2014). We previously reported a FLAG-sequential approach in 6 patients with FA (5 AML and 1 advanced MDS), all alive at a median follow-up of 28 months (Talbot et al., Hematologica 2014). We update here those patients and report 12 more patients treated by FLAG-sequential since then. Materials & Methods: This retrospective study (2006-2019) was conducted in 7 centers in France and Brazil on behalf of the French Reference Center for Aplastic Anemia to evaluate FLAG-sequential in FA patients with morphological clonal evolution (no patients with cytogenetic abnormalities only). The study was conducted in accordance with the Declaration of Helsinki. Anonymous data collection was declared to the appropriate authorities. The FLAG-sequential treatment consisted of FLAG, Fludarabine 30 mg/m²/d for five days and Cytarabine 1 g/m²x2/d with G-CSF for five days, which was followed three weeks later by Cyclophosphamide 10 mg/kg/d for four days, Fludarabine 30 mg/m²/d for four days and TBI 2 Gy (Fig 1A). In a haploidentical setting, Cyclophosphamide at 30 mg/kg/d was performed only in post-transplantation, at Days +4 and +5 (Fig 1B). Results: Eighteen patients were included with 14 AML, 1 acute lymphoblastic leukemia (ALL), and 3 RAEB-2 (Table 1). The median age at the time of HSCT was 22 years (4-37 years). Fifteen patients (83%) were older than 10 years at the time of HSCT. The median follow-up was 31 months (3- 153 months). Eight patients (44%) had complex karyotype. None of the included patients had a history of solid malignancies before HSCT. All patients engrafted. The cumulative incidence of neutrophil engraftment at Day 60 was 94% (95% CI 63-100%) with a median of 18 days (12-343 days). The cumulative incidence of platelet engraftment at Day 60 was 83% (95% CI 50%-96%) with a median of 25 days (17-245 days). The donor chimerism was complete at Day +100 for 15 patients. The three patients without full donor chimerism at Day +100 either had a relapse (n=1) and 2 early deaths before Day+100 from steroid-refractory aGVHD (n=1) or septic shock (n=1). None of the patients received a second HSCT. Non-relapse mortality (NRM) at 3 years was 32% (95% CI 6-58%) (Fig 2). Cumulative incidence of grades II to IV aGVHD was 56% (35% grades III to IV). Cumulative incidence of extensive cGVHD was 16%. Infectious complications during HSCT include the following: CMV (n=8), EBV (n=2), adenovirus (n=4), BK virus (n=7), respiratory syncytial virus (n=1), candidaemias (n=2) and invasive aspergillosis (n=3). Progression free survival (PFS) and OS at 3 years were 53% (95%CI 32-89%) and 53% (95%CI 32-89%), respectively (Fig 2). Cumulative incidence of relapse at 3 years was 13% (95%CI 0-31%) (Fig 2). Seven patients died during the study. Causes of death were relapse (n=2), aGVHD (n=2), cGVHD (n=1), septic shock (n=1), and respiratory syncytial virus associated with invasive aspergillosis (n=1). GVHD-relapse free survival (GRFS) at 3 years was 48% (95%CI 29-78%). One patient had anal epidermoid carcinoma at 4 years after HSCT, which required multiple surgical ablations. Conclusion: With almost 3 years follow-up, which is long enough for our results to be considered robust, we report an OS and PFS of 53%, which compares favorably to historical controls since all of our 18 patients were treated with florid disease at time of HSCT (and not with cytogenetic abnormality only, known to be associated with a better prognosis). Toxicity is still a concern in this particular population of FA patients with notably a high rate of infectious complications. Future well designed prospective clinical trials will refine this sequential strategy, which appears promising in this particular difficult clinical situation. Disclosures Socie: Alexion: Consultancy. Peffault de Latour:Alexion: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

Studies indicate that exercise might delay human biological aging, but the effects of long-term exercise on T cell function are not well known. We tested the hypothesis that moderate or intense exercise lifestyle may attenuate the effects of aging on the telomere length and the survival and composition of T cell subpopulations. Elderly (65-85 years) with intense training lifestyle (IT, n = 15), moderate training lifestyle (MT, n = 16), and who never trained (NT, n = 15) were studied. Although the three groups presented the age-associated contraction of the TCD4(+)/TCD8(+) naïve compartments and expansion of the memory compartments, both training modalities were associated with lower proportion of terminally differentiated (CD45RA(+)CCR7(neg)) TCD4(+) and TCD8(+) cells, although among the latter cells, the reduction reached statistical significance only with IT. MT was associated with higher proportion of central memory TCD4(+) cells, while IT was associated with higher proportion of effector memory TCD8(+) cells. However, both training lifestyles were unable to modify the proportion of senescent (CD28(neg)) TCD8(+) cells. Telomeres were longer in T cells in both training groups; with IT, telomere length increased mainly in TCD8(+) cells, whereas with MT, a modest increase in telomere length was observed in both TCD8(+) and TCD4(+) cells. Reduced commitment to apoptosis of resting T cells, as assessed by caspase-3 and Bcl-2 expression, was seen predominantly with IT. Measurement of pro-inflammatory cytokines in serum and peripheral blood mononuclear cell (PBMC)'s supernatants did not show chronic low-grade inflammation in any of the groups. In conclusion, MT and IT lifestyles attenuated some of the effects of aging on the immune system.

En los corazones humanos la dominancia coronaria es derecha. Sin embargo, no encontramos referencias en la literatura sobre los indicadores de esta dominancia en perros. Utilizamos 30 corazones de perros de ambos sexos y raza mixta, fijados en formaldeido al 10%. Las ramas de las arterias coronarias fueron disecadas con especial atencion a los niveles considerados como referencias. En 96,7% de los corazones, la rama circunfleja de la arteria coronaria izquierda excedio o llego a la crux cordis. La arteria interventricular subsinuosa, termino antes de llegar al apice en 21 casos, en el apice en 5 casos y despues del apice en 4 casos. La arteria interventricular paraconal, termino antes de llegar al apice en 2 casos, en el apice en 11 casos y despues del apice en 17 casos. La region del apice del corazon estaba irrigada por ramas de la arteria coronaria izquierda a traves de la rama interventricular paraconal o a traves de los dos ramas interventriculares. La longitud media y el numero de ramas ventriculares de la arteria coronaria izquierda son mas grandes que las ramas de la arteria coronaria derecha. La rama interventricular subsinuosa es una rama de la rama circunfleja de la arteria coronaria izquierda. En los corazones de los perros, sin embargo, la dominancia es izquierda. La norma de dominancia en los perros es diferente de la norma de dominancia en humanos encontrada en la literatura.

We aimed to verify whether different levels of training performed regularly and voluntarily for many years could have an impact on one of the main issues of immunosenescence: the poor response to vaccines. We recruited 61 healthy elderly men (65-85 years old), 23 with a moderate training (MT) lifestyle (for 17.0 ± 3.2 years), 22 with an intense training (IT) lifestyle (for 25.9 ± 3.4 years), and 16 without a training lifestyle (NT). Fitness was evaluated through the IPAQ and VO2max consumption. The participants were evaluated regarding cognitive aspects, nutritional status, depression, and quality of life. Antibody titers were determined by hemagglutination inhibition assay prior to influenza vaccination and at 6 weeks and 6 months post-vaccination. Strains used were B, H3N2, and H1N1. Our groups were matched for most characteristics, except for those directly influenced by their lifestyles, such as BMI, VO2max, and MET. In general, MT and IT elderly men showed significantly higher antibody titers to the three vaccine strains post-vaccination than NT elderly men. There were also higher titers against B and H1N1 strains in the trained groups before vaccination. Additionally, there were higher proportions of seroprotected (titers ≥1:40) individuals in the pooled trained groups both at 6 weeks (B and H3N2, p

on behalf of Eurocord, Cord Blood Committee EBMT and Netcord; International audience; Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.

La duplicacion de las venas gonadales es mas comun en el lado izquierdo, con pocos casos bilaterales. El proposito de este reporte fue describir el caso de una duplicacion bilateral de las venas gonadales, dos de las cuales desembocaban en la vena cava inferior. El vaso proximo del margen medial del rinon tenia un diametro de 2,68mm y una longitud de 64,41 mm. La segunda vena tenia un diametro de 1,43 mm y una longitud de 73,76 mm. Los dos vasos desembocaban en la vena renal izquierda. La primera vena tenia un diametro de 2,7 mm y estaba a 21,8 mm del margen medial del rinon. La otra tenia un diametro de 1,64 mm y se se localizaba a 35,13 mm del margen medial del rinon. La presencia de variaciones donde se produce el drenaje de los vasos gonadales tiene importancia clinica para la comprension del origen del varicocele y la recurrencia del mismo, despues de procedimientos quirurgicos.

Graft failure (GF) can be a fatal complication following haematopoietic stem cell transplantation (HSCT). We report four patients who developed early GF after unrelated HSCT and who subsequently received a double unrelated cord blood transplant (dUCBT) after reduced-intensity conditioning, at a median 15 d after the decision to perform a second transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimaerism of one unit. Acute GVHD grades II-IV was observed in three patients. Three are alive, between 12 and 25 months after dUCBT. In conclusion, dUCBT is a promising procedure to treat early GF.

OBJECTIVE: To compare sleepiness scores of the Epworth scale in patients with different levels of arterial pressure when undergoing outpatient monitoring within the context of clinical evaluation. METHODS: A total of 157 patients selected for outpatient monitoring of arterial pressure during hypertension evaluation were divided into 3 groups: group 1 - normotensive; group 2 - hypertensive; group 3 - resistant hypertensive. For analysis, values > or = 11 were considered as associated with respiratory disturbances during sleep. RESULTS: Seventeen (10.8%) patients in group 1, 112 (71.3%) in group 2, and 28 (17.8%) in group 3, which was composed of aged, more severely hypertensive individuals, were analyzed. Groups were similar relative to sex and body mass index, but different in relation to systolic and diastolic pressure levels and age. Despite an absolute difference, no statistically significant difference occurred between Epworth scores and in the proportion of patients with values > or = 11 (5.9% vs. 18.8% vs. 212.4%; P=0.37). Despite the positive association between degree of sleepiness measured with the scale and the severity of the hypertension, no statistical significance occurred following control by age (p=0.18). CONCLUSION: A positive correlation exists between degree of sleepiness and hypertension severity. The absence of a statistical significance shown in the present study could be due to a beta type of error. Instruments that render this complaint into an objective finding could help in the pursuit of an investigation of respiratory disturbances during sleep in more severely hypertensive patients, and should therefore be studied better.