Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis

Binary systems and their nuclear explosions

Peer ReviewedPreprin

A survey of pediatricians' attitudes regarding influenza immunization in children

<p>Abstract</p> <p>Background</p> <p>The Advisory Committee on Immunization Practices advocates that influenza immunization is the most effective method for prevention of illness due to influenza. Recommendations for vaccination of children against influenza have been revised several times since 2002, and as of 2008 include all children 6 months to 18 years of age. Nevertheless, influenza immunization rates have remained low.</p> <p>Methods</p> <p>We surveyed practicing pediatricians in Maryland in the spring of 2007 to determine their attitudes and practices toward childhood influenza immunization.</p> <p>Results</p> <p>The overall response to the survey was 21%. A total of 61% of respondents reported that immunization either is cost neutral or produces a loss, and 36.6% noted it was minimally profitable. Eighty-six percent of respondents were receptive to supporting school-based immunization programs, and 61% indicated that they would participate in such programs. Respondents reported higher rates of immunization of select patient groups than those noted by the Centers for Disease Control and Prevention</p> <p>Conclusion</p> <p>Vaccination was reported to occur at multiple types of patient encounters, as recommended. Survey respondents stated that practice-based immunization was not a profitable service. Pediatricians were supportive of school-based immunization programs, and more than half stated they would be actively involved in such programs. School-based programs may be critical to achieving high vaccination coverage in the school-aged population.</p

Successful outcome of six-level cervicothoracic corpectomy and circumferential reconstruction: case report and review of literature on multilevel cervicothoracic corpectomy

The authors report the successful outcome of a six-level corpectomy across the cervico-thoracic spine with circumferential reconstruction in a patient with extensive osteomyelitis of the cervical and upper thoracic spine. To the authors’ knowledge, this is the first report of a corpectomy extending across six levels of the cervico-thoracic spine. Clinical relevance: the authors recommend anterior cage and plate-assisted reconstruction and additional posterior instrumentation using modern spinal surgical techniques and implants

Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis

Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca(2+)-regulated fusion with the plasma membrane.To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky-Pudlak syndrome (HPS) and Griscelli syndrome. In humans, these disorders are characterized by hypopigmentation and immunological alterations that are caused by defects in the biogenesis and trafficking of MVBs and other lysosome related organelles. Neonatal mice for these disease models lacking functional AP-3, Rab27A and BLOC factors were infected with Moloney MLV and the spread of virus into bone marrow, spleen and thymus was monitored. We found a moderate reduction in MLV infection levels in most mutant mice, which differed by less than two-fold compared to wild-type mice. In vitro, MLV release form bone-marrow derived macrophages was slightly enhanced. Finally, we found no evidence for a Ca(2+)-regulated release pathway in vitro. Furthermore, MLV replication was only moderately affected in mice lacking Synaptotagmin VII, a Ca(2+)-sensor regulating lysosome fusion with the plasma membrane.Given that MLV spreading in mice depends on multiple rounds of replication even moderate reduction of virus release at the cellular level would accumulate and lead to a significant effect over time. Thus our in vivo and in vitro data collectively argue against an essential role for a MVB- and secretory lysosome-mediated pathway in the egress of MLV

Independent policy learning: Contextual diffusion of active labour market policies

This chapter analyses in which ways diffusion based on interdependent policy learning explains the spread of active labour market policies (ALMP) in the OECD countries. By applying error correction models using multiplicative spatial Prais-Winsten regressions for analyzing the diffusion of ALMPs in 22 OECD countries from 1991–2013, we find evidence of governments adapting labour market policy strategies that have proven successful, that is, perform well in increasing labour market participation in other countries. However, interdependent learning is conditional on the institutional framework: policymakers rather learn from the experience of other countries in the same welfare regime. Even more importantly, the results bear witness to the importance of the European Employment Strategy (EES) as an international coordination framework facilitating policy learning

Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by hypopigmentation, severe immunologic deficiency with neutropenia and lack of natural killer (NK) cells, a bleeding tendency and neurologic abnormalities1–4. Most patients die in childhood. The CHS hallmark is the occurrence of giant inclusion bodies and organelles in a variety of cell types, and protein sorting defects into these organelles5–8. Similar abnormalities occur in the beigemouse6,7,9–13, the proposed model for human CHS. Two groups have recently reported the identification of the beige gene14,15, however the two cDNAs were not at all similar. Here we describe the sequence of a human cDNA homologous to mouse beige, identify pathologic mutations and clarify the discrepancies of the previous reports. Analysis of the CHS polypeptide demonstrates that its modular architecture is similar to the yeast vacuolar sorting protein, VPS15