Incidence of pertussis in subjects aged 50 years and older in France in 2013–2014

Objective

To assess the incidence of pertussis (whooping cough) in subjects aged 50 years and older in France.

Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe₂O₃ NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe₂O₃ NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe₂O₃ NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.     

Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules

Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies.     

TMS of the occipital face area modulates cross-domain identity priming

Brain Structure and Function - Accumulating evidence suggests that besides its function in early facial feature processing, the role of the right occipital face area (rOFA) extends to higher level,...     

High Graft-versus-Host Disease-Free,Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged ≥40 years had a higher transplant-related mortality (29.4% versus 7.8%; P = .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (P = .022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged ≥40 years is problematic, and clinical trials addressing this issue are warranted.     

Survival and Functional Outcomes in Boys with Cerebral Adrenoleukodystrophy with and without Hematopoietic Stem Cell Transplantation

Cerebral adrenoleukodystrophy (CALD) is a rapidly progressing, often fatal neurodegenerative disease caused by mutations in the ABCD1 gene, resulting in deficiency of ALD protein. Clinical benefit has been reported following allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a large multicenter retrospective chart review to characterize the natural history of CALD, to describe outcomes after HSCT, and to identify predictors of treatment outcomes. Major functional disabilities (MFDs) were identified as having the most significant impact on patients’ abilities to function independently and were used to assess HSCT outcome. Neurologic function score (NFS) and Loes magnetic resonance imaging score were assessed. Data were collected on 72 patients with CALD who did not undergo HSCT (untreated cohort) and on 65 patients who underwent transplantation (HSCT cohort) at 5 clinical sites. Kaplan-Meier (KM) estimates of 5-year overall survival (OS) from the time of CALD diagnosis were 55% (95% confidence interval [CI], 42.2% to 65.7%) for the untreated cohort and 78% (95% CI, 64% to 86.6%) for the HSCT cohort overall (P?=?.01). KM estimates of 2-year MFD-free survival for patients with gadolinium-enhanced lesions (GdE⁺) were 29% (95% CI, 11.7% to 48.2%) for untreated patients (n?=?21). For patients who underwent HSCT with GdE⁺ at baseline, with an NFS ≤1 and Loes score of 0.5 to ≤9 (n?=?27), the 2-year MFD-free survival was 84% (95% CI, 62.3% to 93.6%). Mortality rates post-HSCT were 8% (5 of 65) at 100days and 18% (12 of 65) at 1 year, with disease progression (44%; 7 of 16) and infection (31%; 5 of 16) listed as the most common causes of death. Adverse events post-HSCT included infection (29%; 19 of 65), acute grade II-IV graft-versus-host disease (GVHD) (31%; 18 of 58), and chronic GVHD (7%; 4 of 58). Eighteen percent of the patients (12 of 65) experienced engraftment failure after their first HSCT. Positive predictors of OS in the HSCT cohort may include donor-recipient HLA matching and lack of GVHD, and early disease treatment was predictive of MFD-free survival. GdE⁺ status is a strong predictor of disease progression in untreated patients.? This study confirms HSCT as an effective treatment for CALD when performed early. We propose survival without MFDs as a relevant treatment goal, rather than solely assessing OS as an indicator of treatment success.     

Impact of Body Mass Index on Outcomes of Hematopoietic Stem Cell Transplantation in Adults

This retrospective analysis of 2503 adult (age ≥20 years) allogeneic hematopoietic cell transplantation (HCT) recipients assessed the effect of body mass index (BMI) on transplantation outcomes. The median patient age was 51.7years. Patients with both nonmalignant and malignant diagnoses were included. Patients received either a myeloablative (52%) or a reduced-intensity (48%) conditioning regimen. Donors were either related (42%) or unrelated (58%). Cord blood recipients were excluded. Granulocyte colony-stimulating factor-mobilized peripheral blood cells were the stem cell source in 86% of transplantations. Graft-versus-host disease prophylaxis included at least 2 immunosuppressive agents, 1 of which was a calcineurin inhibitor. Patient groups were categorized as underweight, normal weight, overweight, obese, or very obese based on BMI. Endpoints included day +100 mortality, overall mortality, nonrelapse mortality (NRM), and relapse. Changes in nutritional status, based on laboratory parameters, were also examined. Underweight patients had significantly lower early and overall survival and greater NRM. Very obese patients had increased NRM, which was associated with the intensity of conditioning regimen. With long-term follow-up, increasing NRM was associated with both underweight and obese patients compared with normal-weight individuals. Changes in serum protein and albumin levels did not correlate with BMI. Although enteral nutrition is now recommended for some undernourished patients, the efficacy of enteral or parenteral nutrition has not been well studied. For obese patients, there are no guidelines regarding weight loss before transplantation, and acute weight loss in the pretransplantation period may be detrimental.