Hemodynamic mechanisms underlying prolonged post-faint hypotension

During hypotension induced by tilt-table testing, low presyncopal blood pressure (BP) usually recovers within 1 min after tilt back. However, in some patients prolonged post faint hypotension (PPFH) is observed. We assessed the hemodynamics underlying PPFH in a retrospective study. Seven patients (2 females, aged 31-72 years) experiencing PPFH were studied. PPFH was defined as a systolic BP below 85 mmHg for at least 2 min after tilt back. In 6 out of 7 presyncope was provoked by 0.4 mg sublingual NTG, administered in the 60° head-up tilt position following head-up tilt for 20 min. Continuous BP was monitored and stroke volume (SV) was computed from pressure pulsations. Cardiac output (CO) was calculated from SV × heart rate (HR); and total peripheral resistance (TPR) from mean BP/CO. Left ventricular contractility was estimated by dP/dt (max) of finger pressure pulse. Systolic BP (SYS), diastolic BP (DIAS) and HR during PPFH were lower compared to baseline: SYS 75 ± 14 versus 121 ± 18 mmHg, DIAS 49 ± 9 versus 71 ± 9 mmHg and HR 52 ± 14 versus 67 ± 12 beats/min (p < 0.05). Marked hypotension was associated with a 47% fall in CO 3.1 ± 0.6 versus 5.9 ± 1.3 L/min (p < 0.05) and decreases in dP/dt, 277 ± 77 versus 759 ± 160 mmHg/s (p < 0.05). The difference in TPR was not significant 1.1 ± 0.3 versus 1.0 ± 0.3 MU (p = 0.229). In four patients, we attempted to treat PPFH by 30° head-down tilt. This intervention increased SYS only slightly (to 89 ± 12 mmHg). PPFH seems to be mediated by severe cardiac depressio

Constitutive Expression of TNF-Related Activation-Induced Cytokine (TRANCE)/Receptor Activating NF-κB Ligand (RANK)-L by Rat Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE) also known as Receptor-activating NF-κB ligand (RANKL). TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4high pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4low subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system

Identification of genes transcriptionally responsive to the loss of MLL fusions in MLL-rearranged acute lymphoblastic leukemia

MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (<1 year) is characterized by high relapse rates and a dismal prognosis. To facilitate the discovery of novel therapeutic targets, we here searched for genes directly influenced by the repression of various MLL fusions. Methods For this, we performed gene expression profiling after siRNA-mediated repression of MLLAF4, MLL-ENL, and AF4-MLL in MLL -rearranged ALL cell line models. The obtained results were compared with various already established gene signatures including those consisting of known MLL-AF4 target genes, or those associated with primary MLL-rearranged infant ALL samples. Results Genes that were down-regulated in response to the repression of MLL-AF4 and MLL-ENL appeared characteristically expressed in primary MLL-rearranged infant ALL samples, and often represented known MLL-AF4 targets genes. Genes that were up-regulated in response to the repression of MLL-AF4 and MLL-ENL often represented genes typically silenced by promoter hypermethylation in MLL-rearranged infant ALL. Genes that were aff

Co-Mn oxides supported on hierarchical macro-mesoporous silica for CO and VOCs oxidation

The hierarchical macro-mesoporous silica (MMS) was used for a first time as a support for catalysts for oxidation reactions. The macro-mesoporous silica was synthesized by the emulsions templating mechanism and modified separately or simultaneously using cobalt and manganese oxides. The obtained materials were characterized by different physicochemical methods and tested in the oxidation of CO and n-hexane combustion reactions. The modification of the MMS materials does not change significantly the mesopores characteristics; however, its pores are partially blocked by the oxides. For Co-MM sample agglomerates consisting of Co3O4 with average size of 100−150 nm and small spherical aggregates, encapsulated in the mesopores are formed. The amorphous manganese oxide preferentially fills up the mesopores in Mn-MM sample. Mixed oxide Co-Mn phases situated in the mesoporous network are formed in the bi-component Co-Mn samples. No significant change is observed either in the texture, or in the structural features of the catalysts after reaction. The highest catalytic activity for Co-MM sample in CO and n-hexane oxidation is related to the predomination of Co3+ species on the surface of Co3O4 and the more accessible oxide particles located outside the mesopores. The encapsulation of mixed Co-Mn oxides particles in the pores of the macro-mesoporous silica is responsible for a lower catalytic activity in comparison with that of the mono-component cobalt sample

Control of Spatial Organization of Gold Nanoparticles Using Cylindrical Nanopores of Block Copolymers Films

Abstract In this paper, a sequential process of elaboration of hybrid nanostructured composite films has been proposed. The combination of phase separation in poly(styrene-block-4vinylpyridine) (PS-P4VP) block copolymer leading to the formation of nanopores, and gold nanocolloids synthesis confined in the nanoholes has allowed the facile fabrication of hexagonally arranged gold nanoparticles (NPs) onto silicon wafer. In particular, the nucleation and growth of gold nanoparticles took place within the nanopores, where they are confined in both size and shape the formed Au NPs. The resulting hybrid nanoscomposite has been characterized by Atomic Force Microscopy (AFM) and X-Ray Spectroscopy (XPS). This facile and simple process represents an opened pathway to several technologically important materials fabrication such as hierarchical and ordered crystal architectures. Indeed, the approach based on solvent phase, which is particularly attractive due to its low energy requirement, and the safety and environmentally gentle processing conditions

Adverse late health outcomes among children treated with 3D radiotherapy techniques:Study design of the Dutch pediatric 3D-RT study

Background: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. Aims: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. Methods and Results: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000–2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9–14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. Conclusion: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols.</p

Adverse late health outcomes among children treated with 3D radiotherapy techniques:Study design of the Dutch pediatric 3D-RT study

Background: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. Aims: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. Methods and Results: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000–2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9–14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. Conclusion: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols.</p

Lateral Trunk Motion and Knee Pain in Osteoarthritis of the Knee: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Patients with osteoarthritis of the knee may change their gait in an attempt to reduce loading of the affected knee, thereby reducing pain. Especially changes in lateral trunk motion may be potentially effective, since these will affect the position of the centre of mass relative to the knee, enabling minimization of the load on the knee and thereby knee pain. The aim of the study was to test the hypothesis that a higher level of knee pain is associated with higher lateral trunk motion in patients with knee OA.</p> <p>Methods</p> <p>Fifty-two patients with OA of the knee were tested. Lateral trunk motion was measured during the stance phase of walking with an optoelectronic motion analysis system and a force plate. Knee pain was measured with the VAS and the WOMAC pain questionnaire. Regression analyses were performed to assess the relationship between lateral trunk motion and knee pain.</p> <p>Results</p> <p>It was shown that in bivariate analyses knee pain was not associated with lateral trunk motion. In regression analyses, pain was associated with more lateral trunk motion. In addition, more lateral trunk motion was associated with younger age, being female, higher self-reported knee stiffness and higher maximum walking speed.</p> <p>Conclusion</p> <p>Pain is associated with lateral trunk motion. This association is weak and is influenced by age, gender, self-reported stiffness and maximum walking speed.</p

Transplantation tolerance: lessons from experimental rodent models

Immunological tolerance or functional unresponsiveness to a transplant is arguably the only approach that is likely to provide long-term graft survival without the problems associated with life-long global immunosuppression. Over the past 50 years, rodent models have become an invaluable tool for elucidating the mechanisms of tolerance to alloantigens. Importantly, rodent models can be adapted to ensure that they reflect more accurately the immune status of human transplant recipients. More recently, the development of genetically modified mice has enabled specific insights into the cellular and molecular mechanisms that play a key role in both the induction and maintenance of tolerance to be obtained and more complex questions to be addressed. This review highlights strategies designed to induce alloantigen specific immunological unresponsiveness leading to transplantation tolerance that have been developed through the use of experimental models