Conectividade estrutural do cérebro

Mestrado em Radiações Aplicadas às Tecnologias da Saúde. Área de especialização: Ressonância MagnéticaPerceber a rede estrutural formada pelos neurónios no cérebro a nível da macroescala é um desafio actual na área das neurociências. Neste estudo analisou-se a conectividade estrutural do cérebro humano em 22 indivíduos saudáveis e em 2 doentes com epilepsia pós-traumática. Avaliaram-se as diferenças entre estes dois grupos. Também se pesquisaram diferenças a nível do género e idade no grupo de indivíduos saudáveis e os que têm valores médios mais elevados nas medidas de caracterização da rede. Para tal, desenvolveu-se um protocolo de análise recorrendo a diversos softwares especializados e usaram-se medidas da Teoria dos Grafos para a caracterização da conectividade estrutural entre 118 regiões encefálicas distintas. Dentro do grupo dos indivíduos saudáveis concluiu-se que os homens, no geral, são os que têm média mais alta para as medidas de caracterização da rede estrutural. Contudo, não se observaram diferenças significativas em relação ao género nas medidas de caracterização global do cérebro. Relativamente à idade, esta correlaciona-se negativamente, no geral, com as medidas de caracterização da rede estrutural. As regiões onde se observaram as diferenças mais importantes entre indivíduos saudáveis e doentes são: o Sulco Rolândico, o Hipocampo, o Pré-Cuneus, o Tálamo e o Cerebelo em ambos os lados. Estas diferenças são consistentes com as imagens radiológicas dos doentes e com a literatura estudada sobre a epilepsia pós-traumática. Prevêem-se desenvolvimentos para o estudo da conectividade estrutural do cérebro humano, uma vez que a sua potencialidade pode ser combinada com outros métodos de modo a caracterizar as desordens dos circuitos cerebrais. ABSTRACT - Understanding the large-scale structural network formed by neurons is a major challenge in neuroscience. In this study we analyzed the structural connectivity of the human brain in 22 healthy subjects and in 2 patients with post-traumatic epilepsy. We evaluated the differences between these two groups. We also investigated differences in gender and age group of healthy individuals and and those with higher average values in the measures to characterize the network. For this purpose, we developed a protocol analysis using various specialized software and we used measures of graph theory to characterize the structural connectivity between 118 different brain regions. Within the group of healthy subjects we found that men in general are those with higher average measures for the characterization of the structural network. However, there were no significant differences in gender in relation to measures of global characterization of the brain. With regard to age, this is negatively correlated, in general, with measures that characterize the structural network. The brain regions where the most important differences were observed between healthy and patients were: the Rolandic sulcus, the hippocampus, the Pre-Cuneus, thalamus and cerebellum on both sides. These differences are consistent with the radiologic images of patients and the studied literature on post-traumatic epilepsy. Developments are expected to study the structural connectivity of the human brain, since its potential can be combined with other methods to characterize the disorders of the brain circuits

Structural connectivity of the brain: differences between a normal brain and a brain with pathology

Understanding the large-scale structural network formed by neurons is a major challenge in neuroscience. In this study we analyzed the structural connectivity of the human brain in 22 healthy subjects and in two patients with post-traumatic epilepsy. We evaluated the differences between these two groups. We also investigated differences in connectivity regarding gender and age in healthy individuals. For this purpose, we developed an analysis protocol using specialized software applications and we used graph theory metrics to characterize the structural connectivity between 118 different brain regions. Within the group of healthy subjects we found that men in general are those with higher average values of graph theory metrics. However, there were no significant differences in gender regarding global characterization of the brain. In addition, age was, in general, negatively correlated to the connectivity metrics. The brain regions where the most important differences were observed between healthy individuals and patients were: the Rolandic sulcus, the hippocampus, the pre-cuneus, the thalamus and the cerebellum bilaterally. These differences were consistent with theradiologic images of patients and the studied literature on post-traumatic epilepsy. Developments are expected for the study of the structural connectivity of the human brain, since its potential can be combined with other methods to characterize the disorders of brain circuits

Influence of the Seasonal Thermocline on the Vertical Distribution of Larval Fish Assemblages Associated with Atlantic Bluefin Tuna Spawning Grounds

Temperature is often an important variable influencing the vertical position of fish larvae in the water column. The same species may show different vertical distributions in areas with a strong near-surface seasonal thermocline compared to isothermal near-surface regions. In areas with a strong surface thermocline, tuna larvae show a significant preference for the near-surface warmer layers. Little is known regarding larval tuna vertical distribution in isothermal waters and on the vertical distribution of the associated larval fish assemblages. We conducted vertical stratified sampling using the same methodology and fishing device (MOCNESS) in the two major spawning areas of Atlantic bluefin tuna (BFT): western Mediterranean Sea (MED), characterized by a surface thermocline, and the Gulf of Mexico (GOM) which lacks thermal stratification. Tuna larvae occupied the upper 30 m in both areas, but the average larval depth distribution was consistently deeper in the GOM. In the MED, vertical distribution of larval fish assemblages was explained by temperature, and species such as BFT, Thunnus alalunga, and Ceratoscopelus maderensis, among others, coexist above the thermocline and are separated from species such as Cyclothone braueri and Hygophum spp. (found below the thermocline). In the GOM, the environmental correlates of the vertical distribution of the larvae were salinity and fluorescence. Mesopelagic taxa such as Ceratoscopelus spp. and Cyclothone spp., among others, had a shallower average distribution than Lampanyctus spp., Hygophum spp., and Myctophum spp.Versión del edito

Cryopreservation of unrelated donor hematopoietic stem cells: the right answer for transplantations during the COVID-19 pandemic?

Cryopreservation was recommended to ensure continuity of unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) during COVID-19 pandemic. However, its impact on clinical outcomes and feasibility was not well known. We compared 32 patients who underwent UD HSCT using cryopreserved peripheral blood stem cells (PBSC) during the COVID-19 pandemic with 32 patients who underwent UD HSCT using fresh PBSC in the previous period. Median neutrophil engraftment was 17.5 and 17.0 days with cryopreserved and fresh grafts, respectively. Non-significant delays were found in platelet recovery days (25.5 versus 19.0; P = 0.192) and full donor chimerism days (35.0 and 31.5; P = 0.872) using cryopreserved PBSC. The rate of acute graft-versus-host disease at 100 days was 41% (95% CI [21-55%]) in cryopreserved group versus 31% (95% CI [13-46%]) in fresh group (P = 0.380). One-hundred days progression-relapse free survival and overall survival did not differ significantly. During COVID-19 pandemic, six frozen UD donations were not transfused and logistical and clinical issues regarding cryopreservation procedure, packaging, and transporting appeared. In summary, UD HSCT with cryopreserved PBSC was safe during this challenging time. More efforts are needed to ensure that all frozen grafts are transplanted and cryopreservation requirements are harmonized

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience

Allo-SCT is a curative option for selected patients with relapsed/refractory (R/R) MCL, but with significant NRM. We present the long-term results of patients receiving allo-SCT in Spain from March 1995 to February 2020. The primary endpoints were EFS, OS, and cumulative incidence (CI) of NRM, relapse, and GVHD. We included 135 patients, most (85%) receiving RIC. After a median follow-up of 68 months, 5-year EFS and OS were 47 and 50%, respectively. Overall and CR rates were 86 and 80%. The CI of relapse at 1 and 3 years were 7 and 12%. NRM at day 100 and 1 year were 17 and 32%. Previous ASCT and Grade 3-4 aGVHD were associated with a higher NRM. Grade 3-4 aGVHD, donor type (mismatch non-related), and the time-period 2006-2020 were independently related to worse EFS. Patients from 1995-2005 were younger, most from HLA-identical sibling donors, and were pretreated less. Our data confirmed that allo-SCT may be a curative option in R/R MCL with low a CI of relapse, although NRM is still high, being mainly secondary to aGVHD. The arrival of new, highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegate allo-SCT to those fit patients who fail these therapies, far away from the optimal timing of treatment

DOLAMA 200: Effectiveness and Safety of a Dual Therapy with Dolutegravir Plus Lamivudine in Treatment-Experienced HIV-1 Infected Real World Participants in Spain

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles

DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks).

Brief: Real-world data in naïve HIV-1 patients demonstrate that dolutegravir plus lamivudine in a multiple tablet regimen is effective, safe, and satisfactory; it causes moderately increasing weight and abdominal circumference and is administrable on a test-and-treat strategy. Background: Our objectives were to determine the real-life effectiveness and safety of DT with dolutegravir (50 mg/QD) plus lamivudine (300 mg/QD) in a multiple-tablet regimen (MTR) in naïve PLHIV followed up for 48 weeks and to evaluate the compliance and satisfaction of patients. Material and methods: An open, single-arm, multicenter, non-randomized clinical trial from May 2019 through September 2020 with a 48-week follow-up. Results: The study included 88 PLHIV patients (87.5% male) with a mean age of 35.9 years; 76.1% were MSM patients. The mean baseline CD4 was 516.4 cells/uL, with a viral load (VL) of 4.49 log10, and 11.4% were in the AIDS stage. DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I + E138A, and V108I); 12.5% were lost to follow-up. At week 48, 86.3% had V