Electrophysiological actions of zonisamide on striatal neurons: Selective neuroprotection against complex I mitochondrial dysfunction

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A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity.

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Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

Introduction: Microvascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2)-delivery but rarely improves tissue O2 uptake in septic patients. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused-RBCs on microcirculation in septic patients. Methods: In a prospective randomized trial, 20 septic patients were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark-field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2-saturation (StO2) and tissue haemoglobin index (THI) were determined with near-infrared spectroscopy (NIRS), and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage and glycocalyx compounds (syndecan-1, hyaluronan, heparan sulfate) were measured in the serum. Results: No differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When looking at within-group changes, microcirculatory improvement was only observed in patients that received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01) and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2-upslope increased in both groups. StO2 and StO2-downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03). Conclusions: This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in septic patients, although it suggests a more favourable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings. © 2014 Donati et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?

One of the main goals in radiobiology research is to enhance radiotherapy effectiveness without provoking any increase in toxicity. In this context, it has been proposed that electromagnetic fields (EMFs), known to be modulators of proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might control tumor recruitment and, thus, provide therapeutic benefits. Scientific evidence shows that the effects of ionizing radiation on cellular compartments and functions are strengthened by EMF. Although little is known about the potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs described in the literature could support their use to improve radiation effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing radiation effect on tumor cells, improving the effects of RT. The aim of this paper is to review reports of the effects of EMFs in biological systems and their potential therapeutic benefits in radiotherapy.This study was supported by the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (PI08/0728, Fondos FEDER) to M.I. Núñez. F. Artacho-Cordón is supported by the Spanish Ministry of Science and Education (AP2012-2524). A grant from the Fundación Benéfica San Francisco Javier y Santa Cándida, University of Granada, to S. Ríos-Arrabal greatly aided this work. This research was also funded by the San Cecilio University Hospital, Granada

Uma biblioteca em construção: o compromisso com o cliente.

Analisa às estratégias adotadas pelo Sistema Integrado de Bibliotecas da Universidade de São Paulo, tendo em vista os novos conceitos de gestão por projetos e com foco no client

The psychosocial and biomechanical assessment of amputees fitted with commercial multi-grip prosthetic hands

6The scenario of upper-limb prosthetics is rapidly changing: innovative solutions are “moving out” from laboratories to be used by patients in the every-day-life. In particular, prosthetic hands are facing major changes, with the availability of multi-grip options. While these new technologies are potentially effective for patients, they are surely more expensive and complex in terms of mechanics, electronics and cosmetic covering, i.e. aspects that also determine an increase of maintenance costs. Since it is important to provide patients with effective components while keeping costs under control, technology assessment is crucial. In this framework, the aim of this Chapter is to provide an overview of some evaluation tools that were set-up at Centro Protesi INAIL to gain insight into the psychosocial and biomechanical aspects of upper-limb amputees using high-tech prostheses. A case study reporting the application of these tools is also presented, regarding a patient using the Otto-Bock Michelangelo hand. Results highlighted an increased satisfaction with the new multi-grip hand and, remarkably, the new prosthesis triggered a higher level of embodiment, with a mindchanging in the use the previous hand as well. Thanks to pleasant appearance and functional features of Michelangelo, the patient started to assume more natural gestures and postures also with the traditional myoelectric hand, reporting this different way of thinking the prosthesis as “a fundamental step for an amputee”. Regarding the biomechanical assessment, the shoulder biomechanics was positively influenced by the availability of the lateral grip and by the overall hand shape, which allowed the patient to approach cylindrical and coin-shaped objects in a more natural way, limiting the shoulder compensatory movements. Overall, the assessment tools that we set-up provided a valid contribution for the systematic analysis of the changes taking place in the amputee due to the use of new technologies. The broad on-the-field experimentation will ultimately prove the validity of the approach.nonenoneCutti A.G.; Parel I.; Luchetti M.; Gruppioni E.; Rossi N.C.; Verni G.Cutti, A. G.; Parel, Ilaria; Luchetti, M.; Gruppioni, E.; Rossi, N. C.; Verni, G

Clinical outcomes and feasibility of the multidisciplinary management of patients with psoriatic arthritis: two-year clinical experience of a dermo-rheumatologic clinic

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune arthritis, occurring in patients with psoriasis (Pso), that may affect the whole musculoskeletal system but also nails, eye, and gastrointestinal tract. Dermatologists and rheumatologists usually manage Pso and PsA separately, but early diagnosis and integrated management could achieve better outcomes of both skin and musculoskeletal manifestations, thus improving the health-related quality of life (HRQoL) of patients. In this work, we have described a model of integrated dermo-rheumatologic approach for the early diagnosis of PsA and to present the outcomes of the multidisciplinary management of PsA patients after 48 weeks of follow-up. Pso patients complaining musculoskeletal symptoms were enrolled in a DErmo-Rheumatologic Clinic (DERC) in order to screen, classify, and treat patients with PsA, employing an operative working procedure and a specific flowchart. The integrated dermatologic and rheumatologic management of PsA patients allowed a prompt establishment of the diagnosis and the best therapeutic approach in these patients, with a significant improvement of skin and articular diseases and, eventually, a consistent amelioration of HRQoL. Dermatologists and rheumatologists usually manage the "psoriatic disease" in separated outpatient clinics. In our study, we have demonstrated that a combined DERC, by means of a tight cooperation between the dermatologist and the rheumatologist, which use a specific working procedure and treatment flowchart, may achieve the optimal clinical management of these patients, with a consistent clinical remission of the disease and a significant amelioration of the HRQoL

Early CAR- CD4+ T-lymphocytes recovery following CAR-T cell infusion: A worse outcome in diffuse large B cell lymphoma

CAR(-) CD4(+) T cell lymphopenia is an emerging issue following CAR-T cell therapy. We analyzed the determinants of CD4(+) T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR-T for diffuse large B-cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric-flow cytometry. Six-month cumulative incidence of CAR(- )CD4(+) T cell recovery (>= 200 cells/mu L) was 0.43 (95% confidence interval [CI]: 0.28-0.65). Among possible determinants of CD4(+) T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p = 0.016). Higher CD4(+) T cell counts resulted with TSA at month-1, -2 and -3. Moderate-to-severe infections were registered with prolonged CD4(+) T cell lymphopenia. Early, month-1 CD4(+ )T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4.46 [95% CI: 1.12-17.71], p = 0.03). We conclude that a faster CAR(- )CD4(+) T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR(-) CD4(+) T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients

Plasma Free Hemoglobin and Microcirculatory Response to Fresh or Old Blood Transfusions in Sepsis

<div><p>Background</p><p>Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.</p><p>Methods</p><p>This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO₂) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.</p><p>Results</p><p>Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).</p><p>Conclusions</p><p>Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://www.clinicaltrials.gov/ct2/show/NCT01584999" target="_blank">NCT01584999</a></p></div