Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.

BACKGROUND: The exact pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown. OBJECTIVES: We hypothesized that PFAPA might be due to dysregulated monocyte IL-1β production linked to genetic variants in proinflammatory genes. METHODS: Fifteen patients with PFAPA syndrome were studied during and outside a febrile episode. Hematologic profile, inflammatory markers, and cytokine levels were measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to secrete IL-1β was assessed by using ELISA, and active IL-1β secretion was visualized by means of Western blotting. Real-time quantitative PCR was performed to assess cytokine gene expression. DNA was screened for variants of the MEFV, TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome. RESULTS: During a febrile attack, patients with PFAPA syndrome revealed significantly increased neutrophil counts, erythrocyte sedimentation rates, and C-reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12 levels compared with those seen outside attacks. Stimulated PBMCs secreted significantly more IL-1β during an attack (during a febrile episode, 575 ± 88 pg/mL; outside a febrile episode, 235 ± 56 pg/mL; P < .001), and this was in the mature active p17 form. IL-1β secretion was inhibited by ZYVAD, a caspase inhibitor. Similar results were found for stimulated monocytes (during a febrile episode, 743 ± 183 pg/mL; outside a febrile episode, 227 ± 92 pg/mL; P < .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3 variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant. CONCLUSION: Our data strongly suggest that IL-1β monocyte production is dysregulated in patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3 variants, suggesting that inflammasome-related genes might be involved in this autoinflammatory syndrome.

Essential Bacillus subtilis genes.

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximately 4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from bacteria with small genomes. Unexpectedly, most genes involved in the Embden-Meyerhof-Parnas pathway are essential. Identification of unknown and unexpected essential genes opens research avenues to better understanding of processes that sustain bacterial life.

Reduction theorems for operators on the cones of monotone functions

For a quasilinear operator on the semiaxis a reduction theorem is proved on the cones of monotone functions in Lp - Lq setting for 0 < q < ∞, 1<= p < ∞. The case 0 < p < 1 is also studied for operators with additional properties. In particular, we obtain critera for three-weight inequalities for the Hardy-type operators with Oinarov' kernel on monotone functions in the case 0 < q < p <= 1.

Core Functions of the Health Service Report

The Government Decision1 on the Structural, Organisational, Financial Management and Systems Reform of the Health Sector of June, 2003 acknowledged that in order to increase the effectiveness of the health service generally, and its capacity to deliver the reform agenda, it was important that the service was fully concentrated on addressing its core health objectives. The Minister for Health and Children and Minister for Finance felt that there could be scope to transfer certain functions out of the health service and locate them more appropriately within other functional areas of Government. As part of the overall decision, it was agreed that a working group would be established, to include the Departments of Health and Children, Finance and An Taoiseach, to examine the scope for transfer of certain activities to other, more appropriate, Departments and agencies and that on completion of this review, the Minister for Health and Children would bring proposals to Government. Read the Report (PDF, 70kb)  

Troubles cognitifs séquellaires de la rupture d'anévrysmes de l'artère communicante antérieure et de l'artère cérébrale antérieure. Etude rétrospective de 56 cas [Cognitive sequelae following rupture of aneurysms of the anterior communicating artery and the anterior cerebral artery. Retrospective study of 56 cases].

The neuropsychological records of 56 patients operated for clipping were studied. Almost every patient remained autonomous and without invalidating motor defect. The present study was aimed at specifying the type and frequency of neuropsychological sequelae and, to a lesser extent, the role of various pathophysiological factors. A main concern was to examine to what extent and at what post-operative interval the neuropsychological assessment can predict the intellectual and socioprofessional outcome of each individual patient. The neuropsychological assessment performed beyond the acute phase showed evidence of intellectual sequelae in about two thirds of the patients. Only one case of permanent anterograde amnesia was observed, probably due to unavoidable inclusion of a hypothalamic artery in the clip during surgery. Transient anterograde amnesia and confabulations were occasionally observed, generally for less than three weeks. A common finding was impaired performance on memory and/or executive tests. In a minority of patients, language disorders, visuoperceptive and visuoconstructive disabilities were found, probably in relation with hemodynamic changes at distance from the aneurysm. Global impairment of intellectual function was not uncommon in the acute post-operative phase but it evolved in most cases towards a more selective impairment, for instance restricted to executive and memory functions, in the chronic phase. The neuropsychological investigation carried out 4 to 15 weeks post-operatively provided satisfactory information about possible long-lasting intellectual disturbances and professional resumption. In particular, persistent global intellectual impairment, persistent amnesia and confabulations 4-15 weeks post-operative were associated with cessation of professional activity; executive and memory impairment, behavioral disturbances such as those encountered in patients with frontal lobe damage were associated with a decreased probability of full-time employment. Pre- and post-operative angiography were not good predictors of long-term cognitive outcome: normal angiography was not necessarily followed by normal neuropsychological outcome, conversely abnormal angiography could be found together with normal neuropsychological outcome. By contrast, there was a relationship between left-lateralised abnormalities on post-operative angiography and occurrence of language disorders; similarly, there was a relationship between side of craniotomy and type of deficits, that is language disorders versus visuoperceptive-visuoconstructive impairments.

Krein's strings whose spectral functions are of polynomial growth

In case Krein's strings with spectral functions of polynomial growth a necessary and su fficient condition for the Krein's correspondence to be continuous is given.

Effects of corticosterone on innate and humoral immune functions and oxidative stress in barn owl nestlings.

The costs of coping with stressful situations are traded-off against other functions such as immune responses. This trade-off may explain why corticosterone secretion reduces immune reactions. Corticosterone differentially affects various immunity components. However, which component is suppressed varies between studies. It remains unclear whether the trade-off in energy, nutrition, autoimmunity or oxidative stress accounts for differential immunosuppression. In this study, we investigated whether corticosterone differentially affects the constitutive innate and humoral acquired immunity. We used barn owl nestlings, implanting 50% with a corticosterone-releasing pellet and the other 50% with a placebo pellet. To measure the effect on humoral immunity we vaccinated 50% of the corticosterone-nestlings and 50% of the placebo-nestlings with the antigens 'Tetravac' and the other 50% were injected with PBS. To assess the costs of elevated corticosterone, we measured body mass and resistance to oxidative stress. Administration of corticosterone increased corticosterone levels whereas vaccination induced the production of antibodies. Corticosterone reduced the production of antibodies, but it did not significantly affect the constitutive innate immunity. Corticosterone reduced body growth and resistance to oxidative stress. Under stressful conditions barn owl nestlings seem to keep the constitutive innate immunity, whereas elevated corticosterone levels negatively affected inducible immune responses. We found evidence that mounting a humoral immune reaction is not costly in terms of growth, but reduces the resistance to oxidative stress independently of corticosterone administration. We suggest that humoral immunity is suppressed because the risk of immunopathologies may be disproportionately high when mounting an antibody response under stressful situations.

An algebraic operator approach to the analysis of Gerber-Shiu functions

We introduce an algebraic operator framework to study discounted penalty functions in renewal risk models. For inter-arrival and claim size distributions with rational Laplace transform, the usual integral equation is transformed into a boundary value problem, which is solved by symbolic techniques. The factorization of the differential operator can be lifted to the level of boundary value problems, amounting to iteratively solving first-order problems. This leads to an explicit expression for the Gerber-Shiu function in terms of the penalty function.

Fonctions du plancher pelvien: de la phase expulsive à la consultation du post-partum [Pelvic floor functions: from the beginning of the second phase of labor to the postpartum consultation].

Vaginal delivery can cause lesions of the various pelvic structures responsible for the mechanisms of continence. These lesions may perhaps be prevented in the future by measuring pressure generated during childbirth. Tear of the anal sphincter during childbirth is a marker of a global impairment of the urinary, ano-rectal and sexual pelvic functions in the short and medium term. Persistence of a defect of the anal sphincter is frequent in spite of immediate suture. The correlation between these defects and ano-rectal incontinence are not established in our experience. The quality of the contraction of the sphincter complex and pubo-rectal sling seems to play a more important role in ano-rectal continence after a traumatic childbirth.

Almost routine prophylactic cholecystectomy during laparoscopic gastric bypass is safe

Background Morbidly obese patients are at high risk to develop gallstones, and rapid weight loss after bariatric surgery further enhances this risk. The concept of prophylactic cholecystectomy during gastric bypass has been challenged recently because the risk may be lower than reported earlier and because cholecystectomy during laparoscopic gastric bypass may be more difficult and risky. <p>Methods A review of prospectively collected data on 772 patients who underwent laparoscopic primary gastric bypass between January 2000 and August 2007 was performed. The charts of patients operated before 2004 were retrospectively reviewed regarding preoperative echography and histopathological findings.</p> <p>Results Fifty-eight (7.5%) patients had had previous cholecystectomy. In the remaining patients, echography showed gallstones or sludge in 81 (11.3%). Cholecystectomy was performed at the time of gastric bypass in 665 patients (91.7%). Gallstones were found intraoperatively in 25 patients (3.9%), for a total prevalence of gallstones of 21.2%. The age of patients with gallstones was higher than that of gallstone-free patients (43.5 vs 38.7 years, p < 0.0001). Of the removed specimens, 81.8% showed abnormal histologic findings, mainly chronic cholecystitis and cholesterolosis. Cholecystectomy was associated with no procedure-related complication, prolonged duration of surgery by a mean of 19 min (4-45), and had no effect on the duration of hospital stay. Cholecystectomy was deemed too risky in 59 patients (8.3%) who were prescribed a 6-month course of ursodeoxycolic acid.</p> <p>Conclusion Concomitant cholecystectomy can be performed safely in most patients during laparoscopic gastric bypass and does not prolong hospital stay. As such, it is an acceptable form of prophylaxis against stones forming during rapid weight loss. Whether it is superior to chemical prophylaxis remains to be demonstrated in a large prospective randomized study.</p>

Smoking causes mouth cancer, PHA warns

Mouth cancer awareness week begins on the 13 - 20 November. With this in mind the Public Health Agency is urging everyone to be aware of the signs and symptoms of mouth cancer and is encouraging all smokers thinking about stopping smoking to make the decision to stop today.In Northern Ireland 195 people were diagnosed with mouth cancer in 2009. The disease causes one death every five hours in the UK and yet it is one of the least well-known cancers. Smoking and excess alcohol consumption is associated with an increased risk of developing mouth cancer, which can occur in or on any part of the mouth, tongue, lips, neck and throat. In its very early stages, mouth cancer can be easy to ignore. Most people with mouth cancer have no early symptoms at all, but others may have:an ulcer in the mouth or on the lip that won't heal; constant pain or soreness; red or white patches in the mouth;a lump on the lip, tongue or in the neck; bad breath; unexplained bleeding in the mouth; numbness in the mouth; loose teeth.The earlier the disease is caught, the better. Survival rates rise to 90 per cent if the cancer is treated before it has spread. Gerry Bleakney, Head of Health and Social Wellbeing Improvement, PHA, said: "Certain lifestyle choices can increase an individual's risk of developing mouth cancer. Tobacco is considered to be the main cause of mouth cancer, with three in four cases being linked to smoking. Excess alcohol consumption is also a known factor, with those who both smoke and drink excessively being up 30 times more likely to be at risk. "Mouth cancer and the treatment required can be traumatic for the patient as this may affect functions such as speech, chewing and swallowing. The positive news is that stopping smoking is associated with a rapid reduction in the risk of oral cancers. Regular trips to the dentist are also a must because half of all mouth cancer cases are detected by dentists."I would encourage everyone who is thinking about quitting to log on to our Want 2 Stop website www.want2stop.info and order a 'Quit Kit' free of charge. Alternatively contact the Smokers' Helpline on 0808 812 8008. "Health Minister Edwin Poots said: "Smoking is the single greatest cause of preventable illness and premature death in Northern Ireland.It is a major risk factor for oral cancer, as well as coronary heart disease, strokes and other diseases of the circulatory system. Approximately 2,300 people die each year in Northern Ireland from smoking related illnesses. Quitting smoking is the single most effective step people can take to improve their long term health."A key objective of the Department's new ten-year tobacco control strategy, due to be published next month,is to prevent people from starting to smoke. Funding provided by the Department for smoking cessation services has resulted in around 650 such services being made available in Northern Ireland in a range of settings, including pharmacies, GP surgeries and community centres. These services have helped almost 80,000 smokers to set a quit date between 2008/09 and 2010/11."The Minister added: "It is also important for people to look after their oral health by regularly attending the dentist for check-ups, as any problems can be picked up and treated at an early stage."

What Kind of Justice Today ? Expectations Of 'Good Justice', Convergences And Divergences Between Managerial And Judicial Actors And How They Fit Within Management-Oriented Values

This research aims toward a better understanding of the organizational culture(s) of the judiciary in Switzerland by analysing what 'good justice' means nowadays in this country. It seeks to clarify whether, and to what extent, expectations of 'good justice' of judicial actors (judges without managerial experience) and of managerial actors (court managers) are similar and to describe possible managerial implications that may result from this. As judges are at the heart of the judicial organization and exert a strong influence on other groups of actors (Sullivan, Warren et al. 1994), the congruence of their expectations with those of court managers will be at the centre of the analysis. Additionally, referring to the conceptual worlds of Boltanski and Thévenaut (1991), we analyze how closely these expectations are to management-oriented values. We found that almost half of expectations are common to the two groups examined and the main quoted ones are compatible to new public management (NPM) concepts. On the other hand, those expectations shared exclusively by judges relate to the human side of justice, whereas those specific to court managers focus on the way justice functions.

Suppression of Brugia malayi (sub-periodic) larval development in Aedes aegypti (Liverpool strain) fed on blood of animals immunized with microfilariae

Preliminary studies were carried out to investigate the role of filarial specific antibodies, raised in an animal model against the filarial parasite, Brugia malayi (sub-periodic), in blocking their early development in an experimental mosquito host, Aedes aegypti (Liverpool strain). In order to generate filarial specific antibodies, Mongolian gerbils, Meriones unguiculatus, were immunized either with live microfilariae (mf) of B. malayi or their homogenate. Mf were harvested from the peritoneal cavity of Mongolian gerbils with patent infection of B. malayi and fed to A. aegypti along with the blood from immunized animals. Development of the parasite in infected mosquitoes was monitored until they reached infective stage larvae (L3). Fewer number of parasites developed to first stage (L1) and subsequently to L2 and L3 in mosquitoes fed with blood of immunized animals, when compared to those fed with blood of control animals. The results thus indicated that filarial parasite specific antibodies present in the blood of the immunized animals resulted in the reduction of number of larvae of B. malayi developing in the mosquito host.