Increased expression of Tbet in CD4+ T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS

BACKGROUND: The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4(+) T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation. Upon activation, CD4(+) T cells can differentiate into various subsets depending on the milieu present. Th1 and Th17 cells are strongly implicated in MS, while regulatory T (Treg) cells constrain autoimmune inflammation and prevent autoimmunity. FINDINGS: We therefore investigated the expression of TOB1, CD44 and Treg, Th1 and Th17 transcription factors in relation to CIS progression. The expression of TOB1, CD44, FOXP3, TBX21 and RORC genes were measured in CD4(+) T cells from 10 healthy controls, 20 CIS patients within 3 months of initial clinical presentation and 10 relapsing remitting MS patients sampled within 2 months of relapse. CIS patients were subsequently grouped into those who converted to CDMS within 1 year and those who remained CIS. No differences in the expression of TOB1, CD44, FOXP3 and RORC were observed. There was a significant increase in the expression of the Th1 transcription factor Tbet, encoded by TBX21, in CIS patients that converted within 1 year compared with those who did not. CONCLUSION: This pilot data suggests a role for Th1 cells in CIS progression and warrants further evaluation in a larger cohort

Beckett's Spectral Silence: Breath and the Sublime

Of Samuel Beckett’s late plays, the one that most eloquently resists presentation, that retires from visibility, remaining almost completely hidden except for faint light and a brief cry over a glimpse of detritus is Breath. Though regarded as a ‘logical terminal point in Beckett’s writing for theatre’ when it appeared, it wrong-footed critical expectation, pointing instead to the much reduced plays of the 1970s. The paper examines Beckett’s Breath, theatre productions of the play––in particular that of Amanda Coogan––and the film version of Breath directed by Damien Hirst, in terms of Kant’s analytic of the sublime, in particular Kant’s idea of the sublime as that which is beyond the limits of size and representability. Drawing on Longinus, Lyotard and Derrida, the paper argues, through Beckett, for a reconfiguration of the sublime in terms of an absolute minimum

The Werewolf: From Damned Degradation to Romantic Reversion

One can better understand the evolving role of the werewolf in folklore by examining its development over time. This development has constantly shifted to address multifarious needs, underpinned by equally transformative religious systems. Where religion has gone, so too has the werewolf. Each of the transformations the werewolf has undergone abstractly mirrors the prevailing religious and spiritual conditions – fears, anxieties, and desires – at the time. This essay begins by focusing on the earliest accounts of the werewolf stories where man’s expressed apprehension of the wild supplied the rudimentary components from which said stories were composed. Imagined out of fear and anxiety, werewolves were an aggrandizement of wolves proper, already contextualized in early human life. The werewolf then developed as a tool with which man could communicate his relationship with the natural world and the place he had in it. The utility of the werewolf became ever more direct under the influence of large religious bodies, chiefly Christianity. In this religious milieu, the idea of man degraded to his natural state became channeled through the werewolf’s beastly, yet uncanny human qualities. Now occupying an intermediary place between what men then viewed as natural depravity and their ideals regarding morality and civility, the werewolf represented man’s tendency to regress into wanton behaviors of previous times. The last part of the essay charts the course werewolves have hitherto taken in contemporary works of literature. Having departed from religion’s dominating sphere of influence, modern interpretations of the werewolf have lost the qualities of baseness, depravity, and carnal immorality in the truest sense. Added on to the list of meanings communicated by werewolves are the myriad environmental issues found in modern political and scientific discourse, breaching more and more into the secular realm. While all evolutions of the werewolf are valid in their respective contexts, ultimately, none offers ample satisfaction of or answers to the concerns they address. Instead, the metamorphoses temporarily assuage the spiritual and religious needs of human thought. What each progression of the werewolf has in common rests in the cycle of tension and uncertainty that mankind unendingly labors to cope with by telling captivating stories

Post-Partum Pituitary Insufficiency and Livedo Reticularis Presenting a Diagnostic Challenge in a Resource Limited Setting in Tanzania: A Case Report, Clinical Discussion and Brief Review of Existing Literature.

Pituitary disorders following pregnancy are an important yet under reported clinical entity in the developing world. Conversely, post partum panhypopituitarism has a more devastating impact on women in such settings due to high fertility rates, poor obstetric care and scarcity of diagnostic and therapeutic resources available. A 37 year old African female presented ten years post partum with features of multiple endocrine deficiencies including hypothyroidism, hypoadrenalism, lactation failure and secondary amenorrhea. In addition she had clinical features of an underlying autoimmune condition. These included a history of post-partum thyroiditis, alopecia areata, livedo reticularis and deranged coagulation indices. A remarkable clinical response followed appropriate hormone replacement therapy including steroids. This constellation has never been reported before; we therefore present an interesting clinical discussion including a brief review of existing literature. Post partum pituitary insufficiency is an under-reported condition of immense clinical importance especially in the developing world. A high clinical index of suspicion is vital to ensure an early and correct diagnosis which will have a direct bearing on management and patient outcome

Тактика ведения пациентов при синдроме Мэллори-Вейсса

МЭЛЛОРИ-ВЕЙСА СИНДРОМ /диагн /терПИЩЕВОДА ПЕРФОРАЦИЯ /диагн /терЖЕЛУДОЧНО-КИШЕЧНОЕ КРОВОТЕЧЕНИЕГЕМОСТАЗ ЭНДОСКОПИЧЕСКИ

Predictable stimulus onsets improve memory

Exploring and remembering are fundamental to many human activities. Characterizing influences on recognitionmemory can help clarify the workings of memory systems and facilitate design of effective learning environments. Studies ofself-directed learning show that a key determinant of self-directed benefits is in choosing when to see the next stimulus, butthese results do not establish whether it is the act of choosing or the knowledge of stimulus arrival times that primarily matters.We disentangle these factors by asking whether predictable stimulus timing that is not under participant control still leads to amemory benefit. Participants saw pictures of objects one at a time with either a constant or unpredictable inter-stimulus interval(ISI) and showed better memory with constant timing across a range of ISIs. These results speak to interactions betweenattention and memory, the efficiency of study protocols, and the factors influencing effective self-directed learning

Which drugs are most effective for recurrent herpes labialis?

Evidence based answer: Daily oral acyclovir or valacyclovir may help prevent herpes simplex labialis (HSL) recurrences (strength of recommendation [SOR]: B, meta-analysis of randomized controlled trials [RCTs] with heterogeneous results). No trials compare oral or topical treatments for HSL outbreaks against each other. Oral antivirals modestly reduce healing time and duration of pain, varying according to the agent used: valacyclovir reduces both healing time and duration of pain, famciclovir reduces both in one dosage form but not another, and acyclovir reduces only pain duration (SOR: B, single RCTs). Several topical medications (acyclovir, penciclovir, docosanol) modestly decrease healing time and pain duration--typically by less than a day-- and require multiple doses per day (SOR: B, multiple RCTs)