The Blood Brain Barrier and Neuropsychiatric Lupus: New perspectives in light of advances in understanding the neuroimmune interface

Publication date: Available online 17 April 2017
Source:Autoimmunity Reviews
Author(s): Ariel D. Stock, Sivan Gelb, Ofer Pasternak, Ayal Ben-Zvi, Chaim Putterman
Experts have previously postulated a linkage between lupus associated vascular pathology and abnormal brain barriers in the immunopathogenesis of neuropsychiatric lupus. Nevertheless, there are some discrepancies between the experimental evidence, or its interpretation, and the working hypotheses prevalent in this field; specifically, that a primary contributor to neuropsychiatric disease in lupus is permeabilization of the blood brain barrier. In this commonly held view, any contribution of the other known brain barriers, including the blood-cerebrospinal fluid and meningeal barriers, is mostly excluded from the discussion. In this review we will shed light on some of the blood brain barrier hypotheses and try to trace their roots. In addition, we will suggest new research directions to allow for confirmation of alternative interpretations of the experimental evidence linking the pathology of intra-cerebral vasculature to the pathogenesis of neuropsychiatric lupus.



http://ift.tt/2pqbdi8

Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: A systematic review

Publication date: Available online 17 April 2017
Source:Autoimmunity Reviews
Author(s): Bernd Merkel, Helmut Butzkueven, Anthony L. Traboulsee, Eva Havrdova, Tomas Kalincik
BackgroundImmunotherapy initiated early after first presentation of relapsing-remitting multiple sclerosis is associated with improved long-term outcomes. One can therefore speculate that early initiation of highly effective immunotherapies, with an average efficacy that is superior to the typical first-line therapies, could further improve relapse and disability outcomes. However, the most common treatment strategy is to commence first-line therapies, followed by treatment escalation in patients who continue to experience on-treatment disease activity. While this monitoring approach is logical, the current lack of effective regenerative or remyelinating therapies behoves us to consider high-efficacy treatment strategies from disease onset (including induction therapy) in order to prevent irreversible disability.ObjectiveIn this systematic review, we evaluate the effect of high-efficacy immunotherapies at different stages of MS.MethodsA systematic review of literature reporting outcomes of treatment with fingolimod, natalizumab or alemtuzumab at different stages of MS was carried out.Results and conclusionsTwelve publications reporting relevant information were included in the systematic review. The literature suggests that treatment with high-efficacy immunotherapies is more potent in suppressing relapse activity when initiated early vs. with a delay after the MS diagnosis. The evidence reported for disability and MRI outcomes is inconclusive.



http://ift.tt/2ppX3xG

For Keeping X Chromosomes Active, Chromosome 19 Marks The Spot

After nearly 40 years of searching, Johns Hopkins researchers report they have identified a part of the human genome that appears to block an RNA responsible for keeping only a single X chromosome active when new female embryos are formed, effectively allowing for the generally lethal activation of more than one X chromosome during development. Because so-called X-inactivation is essential for normal female embryo development in humans and other mammals, and two activated X chromosomes create an inherently fatal condition, the research may help explain the worldwide human sex ratio that has slightly favored males over females for as long as science has been able to measure it. The results appear online in the April 12 issue of the journal PLOS ONE.

http://ift.tt/2pJ7TLG

Testosterone Reduces Promiscuity of Female Blue Tits (Cyanistes caeruleus): An Experimental Study

In many animal species, extra-pair copulations (EPCs) are common and can increase fitness in both sexes. In males, EPCs can increase total reproductive output, whereas in females benefits of EPCs can be indirect through improving the genetic quality of their offspring. Males and females of many vertebrates show an increase in levels of the hormone testosterone (T) during the mating period. In males, T plays an important role in regulating mating behaviour including increasing their EPC rate. While much is known about the role of T in male mating behaviour, the role of T in female reproduction remains unclear. To study the influence of T on extra-pair paternity rates in females in a field setting, we created three experimental groups of female blue tits (Cyanistes caeruleus): treated with either T, flutamide (Flu; an androgen receptor blocker) or empty implants before egg laying. Subsequently, we scored the number of extra-pair offspring (EPO) in their broods. We also assessed the attractiveness of females treated with either T or Flu to males in mate choice trials in the laboratory. The overall proportion of EPO was lower for the T-implanted group compared with the control group, whereas Flu had no effect. Given that males did not show a preference for Flu- vs. T-treated females in the mate choice trials, it appears less likely that the reduction in EPO in the T-implanted females was due to a reduction in their attractiveness. T levels may have negatively influenced EPO rate by affecting female within-pair and/or extra-pair mating behaviour. Future behavioural studies should investigate how elevated T levels reduce the number of EPO.

http://ift.tt/2oDHKOM

Le résident européen percevant sa propre aptitude linguistique dans un contexte judiciaire - une première recherche empirique sans prétention

http://ift.tt/2ppZZu7

Predictable food supplies induce plastic shifts in avian scaled body mass

Urbanization constitutes one of the most profound forms of land-use change and strongly affects global biodiversity and ecosystem functioning. Expansion of urban areas typically leads to species loss but may also induce more subtle changes in species dynamics through selection or plasticity. Using a dual correlative (field) and experimental (aviary) approach, we here show that free-ranging urban house sparrows in southern France were smaller and lighter than their rural counterparts after allometric scaling, whereas 2 independent indices of nutritional (feather growth rates) and developmental (feather asymmetry) stress did not vary with urbanization. When subjecting these individuals to urban or rural diets in a highly predictable, controlled setting, rural but not urban sparrows decreased their body mass, independent of diet type, to the extent that initial scaled mass differences between urban and rural birds disappeared by the end of the captive period. By integrating field-and aviary measurements of body size and mass with indices of nutritional and developmental stress, we conclude that the lower scaled body masses of urban birds likely reflect a plastic response to predictable food supplies, possibly mediated through predation. Urban environments therefore do not necessarily constitute nutritionally stressful environments for species that typically cohabit with humans, such as house sparrows.

http://ift.tt/2oDSOf2

Docetaxel and Loplatin Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Locally Advanced SCCHN

Condition:   Locally Advanced Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: Lobaplatin;   Drug: Cisplatin
Sponsor:   Guiyang Medical University
Recruiting - verified April 2017

http://ift.tt/2omJLgR