The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation

The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms

Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: The EURODIAB Prospective Complications Study

Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED. Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED. Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes

The molecular side of Quadrato

Our aim is to analyse changes in the level of neurotrophins (NGF and BDNF) in saliva samples of subjects performing the QMT training. NGF is essential for the development and phenotypic maintenance of neurons in the peripheral nervous system, and plays a pivotal role in relevant functions of cholinergic neurons of the basal forebrain: attention, arousal, motivation, memory and consciousness. ELISA assay and western blotting were utilised to measure NGF immunoreactivity and protein levels in the saliva samples of 25 subjects. We observed NGF decrease by ELISA analysis of saliva samples from QMT trainees (28 days) relative to controls. Western blotting analysis allowed us to determine that proNGF is the molecular form responsible for immunoreactivity, and to confirm the decrease observed. Our hypothesis is that the reduction of proNGF levels induced by QMT training is related to its maturation to NGF and utilisation, possibly favouring neuroplasticity versus neurodegeneration

Increased cerebellar volume and BDNF level following quadrato motor training

Using whole-brain structural measures coupled to analysis of salivary brain-derived neurotrophic factor (BDNF), we demonstrate sensory motor training-induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level

Associations of Class-Time Sitting, Stepping and Sit-to-Stand Transitions with Cognitive Functions and Brain Activity in Children

Previous research showed that children’s physical activity is positively related to executive functions, whilst screen time shows negative associations. However, it is unclear how school-based sitting time and transitions from sitting to standing relate to cognition. We investigated the relationship between class time sitting/stepping/sit-to-stand transitions and cognitive functions in Grade 1−2 children. Overall, 149 children (7.7 ± 0.6 years old, 54% boys) participated. Measures included class time sitting/stepping/sit-to-stand transitions and: (i) response inhibition (i.e., response time and accuracy); (ii) lapses of attention; (iii) working memory; and (iv) brain activity (cortical haemodynamic response). Linear mixed-models, adjusting for age, sex, and clustering at the classroom level, found that more sitting time was associated with higher lapses of attention (β = 0.12, p < 0.05). Children who stepped more had quicker inhibition response time (β = −0.95, p < 0.01); however, they were less accurate in their responses (β = −0.30, p < 0.05) and this was also observed with sit-to-stand transitions (β = −0.26, p < 0.05). No associations were found with brain activity. In conclusion, reducing and breaking up sitting may help keep children focused, but the evidence regarding response inhibition is unclear

Uranium: Propriétés et effets biologiques après contamination interne

Uranium is a radionuclide present in the environment since the origin of the Earth. In addition to natural uranium, recent deposits from industrial or military activities are acknowledged. Uranium's toxicity is due to a combination of its chemical (heavy metal) and radiological properties (emission of ionizing radiations). Acute toxicity induces an important weight loss and signs of renal and cerebral impairment. Alterations of bone growth, modifications of the reproductive system and carcinogenic effects are also often seen. On the contrary, the biological effects of a chronic exposure to low doses are unwell known. However, results from different recent studies suggest that a chronic contamination with low levels of uranium induces subtle but significant levels. Indeed, an internal contamination of rats for several weeks leads to detection of uranium in many cerebral structures, in association with an alteration of short-term memory and an increase of anxiety level. Biological effects of uranium on the metabolisms of xenobiotics, steroid hormones and vitamin D were described in the liver, testis and kidneys. These recent scientific data suggest that uranium could participate to increase of health risks linked to environmental pollution.L’uranium est un radionucléide présent dans l’environnement depuis l’origine de la terre. A cet uranium d’origine naturelle viennent s’ajouter des apports plus récents résultant des activités industrielles et militaires de l’homme. La toxicité de l’uranium résulterait d’une combinaison de ses propriétés chimiques (métal lourd) et radiologiques (émission de rayonnements ionisants). La toxicité aiguë se manifeste chez l’animal par une importante perte de poids et des signes d’atteinte rénale et cérébrale. Une altération de la formation osseuse, une modification du système reproducteur et des effets carcinogènes sont également couramment observés. A contrario, les effets biologiques d’une exposition chronique à de faibles doses sont peu connus. Cependant, les résultats de différentes études récentes suggèrent que la contamination chronique à faible niveau par l’uranium induirait des effets biologiques subtils mais significatifs dans des organes qui ne sont pas connus pour être des organes sensibles à la contamination par l’uranium. C’est le cas du système nerveux central par exemple puisque, récemment, ont été montrées une altération de la mémoire à court terme et une augmentation du niveau d’anxiété, associées à la présence d’uranium dans différentes structures cérébrales chez l’animal (essentiellement rongeur). La grande nouveauté dans la connaissance des effets d’une contamination chronique par l’uranium est la mise en évidence d’effets biologiques de l’uranium sur plusieurs métabolismes majeurs de l’organisme, incluant le métabolisme des médicaments, des hormones stéroïdiennes, de la vitamine D et du fer. Ces données scientifiques récentes suggèrent que l’uranium pourrait participer à l’augmentation des risques sanitaires liés à la pollution de l’environnement

Wireless capsule endoscopy versus ileocolonoscopy for the diagnosis of postoperative recurrence of Crohn's disease: a prospective study

BACKGROUND AND AIMS: Following ileocolonic resection for Crohn's disease (CD), early endoscopic recurrence predicts recurrence of symptoms. The aim of the study was to compare ileocolonoscopy and wireless capsule endoscopy (WCE) for the detection of postoperative recurrence in CD. METHODS: WCE and ileocolonoscopy were performed within six months following surgery in 32 prospectively enrolled patients. Two independent observers interpreted the results of WCE. Recurrence in the neoterminal ileum was defined by a Rutgeerts score ⩾1. When observers at WCE did not concur, WCE results were considered as either true negative or true positive and sensitivity and specificity were calculated according to both assumptions. RESULTS: Recurrence occurred in 21 patients (68%) and was detected by ileocolonoscopy in 19 patients. Sensitivity was 90% and specificity 100%. Sensitivity of WCE was 62% and 76% and specificity was 100% and 90%, respectively, depending on assumptions. There was a correlation between the severity of the lesions measured by both methods (p<0.05). Lesions located outside the scope of conventional endoscopy were detected by WCE in two thirds of patients with excellent interobserver agreement (kappa >0.9) for all lesions with the exception of ulceration (kappa = 0.7). CONCLUSIONS: The sensitivity of WCE in detecting recurrence in the neoterminal ileum was inferior to that of ileocolonoscopy. In contrast, WCE detected lesions outside the scope of ileocolonoscopy in more than two thirds of patients. Additional follow up studies are needed to assess the clinical relevance of such lesions. At the present time, it seems that WCE cannot systematically replace ileocolonoscopy in the regular management of patients after surgery