Desensitization of thermal hyperemia in the skin is reproducible.

OBJECTIVE: Local heating increases skin blood flow SkBF (thermal hyperemia). In a previous study, we reported that a first local thermal stimulus could attenuate the hyperemic response to a second one applied later on the same skin spot, a phenomenon that we termed desensitization. However, other studies found no evidence for desensitization in similar conditions. The aim of the present work was to test whether it was related to differences in instrumentation. METHODS: Twenty-eight healthy young males were studied. Two pairs of heating chambers, one custom-made (our study) and one commercial (other groups), were affixed to forearm skin. SkBF was measured with single-point laser-Doppler flowmetry (LDF) (780nm) in one pair, and laser-Doppler imaging (LDI) (633nm) in the other. A temperature step from 34 to 41°C, was applied for 30minutes and repeated after two hours. RESULTS: During the second thermal challenge, the plateau SkBF was lower than during the first thermal and was observed with each of the four combinations of SkBF measurement techniques and heating equipment (p<0.05 for all conditions, range -9% to -16% of the initial value). CONCLUSION: Desensitization of thermal hyperemia is not specific to peculiar operating conditions.

Role of secretory immunoglobulin A and secretory component in the protection of mucosal surfaces.

The contribution of secretory immunoglobulin A (SIgA) antibodies in the defense of mucosal epithelia plays an important role in preventing pathogen adhesion to host cells, therefore blocking dissemination and further infection. This mechanism, referred to as immune exclusion, represents the dominant mode of action of the antibody. However, SIgA antibodies combine multiple facets, which together confer properties extending from intracellular and serosal neutralization of antigens, activation of non-inflammatory pathways and homeostatic control of the endogenous microbiota. The sum of these features suggests that future opportunities for translational application from research-based knowledge to clinics include the mucosal delivery of bioactive antibodies capable of preserving immunoreactivity in the lung, gastrointestinal tract, the genito-urinary tract for the treatment of infections. This article covers topics dealing with the structure of SIgA, the dissection of its mode of action in epithelia lining different mucosal surfaces and its potential in immunotherapy against infectious pathogens.

Parental Leave and Mothers' Careers: The Relative Importance of Job Protection and Cash Benefits

Job protection and cash benefits are key elements of parental leave (PL) systems. We study how these two policy instruments affect return-to-work and medium-run labour market outcomes of mothers of newborn children. Analysing a series of major PL policy changes in Austria, we find that longer cash benefits lead to a significant delay in return-to-work, particularly so in the period that is job-protected. Prolonged parental leave absence induced by these policy changes does not appear to hurt mothers' labour market outcomes in the medium run. We build a non-stationary model of job search after childbirth to isolate the role of the two policy instruments. The model matches return-to-work and return to same employer profiles under the various factual policy configurations. Counterfactual policy simulations indicate that a system that combines cash with protection dominates other systems in generating time for care immediately after birth while maintaining mothers' medium-run labour market attachment.

DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe.

STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

Neuroscience, quantum indeterminism and the Cartesian soul.

Quantum indeterminism is frequently invoked as a solution to the problem of how a disembodied soul might interact with the brain (as Descartes proposed), and is sometimes invoked in theories of libertarian free will even when they do not involve dualistic assumptions. Taking as example the Eccles-Beck model of interaction between self (or soul) and brain at the level of synaptic exocytosis, I here evaluate the plausibility of these approaches. I conclude that Heisenbergian uncertainty is too small to affect synaptic function, and that amplification by chaos or by other means does not provide a solution to this problem. Furthermore, even if Heisenbergian effects did modify brain functioning, the changes would be swamped by those due to thermal noise. Cells and neural circuits have powerful noise-resistance mechanisms, that are adequate protection against thermal noise and must therefore be more than sufficient to buffer against Heisenbergian effects. Other forms of quantum indeterminism must be considered, because these can be much greater than Heisenbergian uncertainty, but these have not so far been shown to play a role in the brain.

Child sun protection in New Zealand: parental view and societal responsibilities

Issue addressed: Cutaneous melanoma is a significant health problem in New Zealand. Excessive sun exposure in early life increases subsequent risk. This study investigated parental opinions, understanding and practices concerning the sun protection of young children. The study aimed to identify areas where improvements in sun protection may be most needed. Methods: Parents were recruited through licensed childcare centres and kindergartens in Dunedin to take part in semi-structured focus groups. Feedback was obtained from participants in response to summary reports based on audiotapes. Results: Parents noted increased social acceptability of sun protective behaviours and child sunburn was now unacceptable. Past media campaigns were well recalled. The 'time to burn' used in media weather reports was easier to understand than the Ultra Violet Index (UVI), about which more information was wanted. Protective messages were expected to be straightforward, consistent and readily and regularly available. Local radio may provide the most timely, relevant information. There was a perceived lack of authoritative information about sunscreens and sunglasses and a shortage of acceptable protective clothing. Fuller information on sunscreen containers and greater use of UV Protection Factor (UPF) ratings for clothing and Eye Protection Factor (EPF) for sunglasses would assist. The use of shade and rescheduling of activities were scarcely mentioned. Conclusions: Parents were aware of the need for child sun protection but lacked confidence about how best to achieve this. Future health promotion programs should emphasise how optimal protection can be achieved more than why sun protection is needed. Programs should include a repertoire of strategies targeted towards individuals through the education of children and caregivers. They should also aim at achieving modifications in physical and social environments, including appropriate product design and promotion. So what?: The development of a balanced, comprehensive program with environmental components that reinforce protective behaviours has the potential to sustain sun protection among the largest number of children in the longer term.

NALP3 is not necessary for early protection against experimental tuberculosis.

In vitro, Toll-like receptors (TLR)2, 4 and 9 as well as NOD-like receptor 2 critically determine macrophage responses to Mycobacterium tuberculosis (Mtb) infection. However, in low-dose experimental murine tuberculosis, single or multiple deficiencies in TLRs 2, 4, 9 or NOD2 have little, if any, impact on early mycobacterial growth containment, granuloma formation and survival. Here, we analyzed the relevance of NALP3, one component of the danger-signaling inflammasome, for (i) Mtb-induced cytokine secretion in vitro and in vivo, (ii) restriction of Mtb replication in infected organs and (iii) granuloma formation. In the absence of functional NALP3, there was no IL-1beta and IL-18 production in Mtb-infected dendritic cells and macrophages in vitro, whereas secretion of IL-1alpha, IL-12p40 and TNF remained unaffected. After three weeks of infection, NALP3-deficient as well as IL-18-deficient mice were as capable as wildtype mice of restricting Mtb loads at a plateau level within well-differentiated granulomas. In conclusion, despite its involvement in cytokine processing, NALP3 is not essential for induction of protective immunity to Mtb.