Prevalence and characteristics of periodic leg movements during sleep in the general population : the Hypnolaus study

Objective: The aim of this study was to describe the prevalence and characteristics of periodic legs movements of sleep (PLMS) in theadult general population. Methods: Data from 2162 subjects (51.2% women, mean SD age:58, 11 years, range: 40.5-84.4 years) participating in a population-based cohort study (HypnoLaus, Lausanne, Switzerland) wascollected. They completed a series of sleep related questionnaires and underwent polysomnographic recordings at home. PLMS index(PLMSI) was determined according to AASM 2007 criteria. APLMSI>15/h was considered to be of potential clinical significance. Conclusions: PLMS are highly prevalent in the general population. Age, male gender and RLS are independent predictors of a PLMSIhigher than 15/h. Further studies are needed to evaluate the clinical impact of PLMS.

"Periodic crises": Clément Juglar between theories of crises and theories of business cycles

Business cycle theory is normally described as having evolved out of a previous tradition of writers focusing exclusively on crises. In this account, the turning point is seen as residing in Clément Juglar's contribution on commercial crises and their periodicity. It is well known that the champion of this view is Schumpeter, who propagated it on several occasions. The same author, however, pointed to a number of other writers who, before and at the same time as Juglar, stressed one or another of the aspects for which Juglar is credited primacy, including the recognition of periodicity and the identification of endogenous elements enabling the recognition of crises as a self-generating phenomenon. There is indeed a vast literature, both primary and secondary, relating to the debates on crises and fluctuations around the middle of the nineteenth century, from which it is apparent that Juglar's book Des Crises Commerciales et de leur Retour Périodique en France, en Angleterre et aux États-Unis (originally published in 1862 and very much revised and enlarged in 1889) did not come out of the blue but was one of the products of an intellectual climate inducing the thinking of crises not as unrelated events but as part of a more complex phenomenon consisting of recurring crises related to the development of the commercial world - an interpretation corroborated by the almost regular occurrence of crises at about 10-year intervals.

Periodic accumulation of cdc15 mRNA is not necessary for septation in Schizosaccharomyces pombe.

Analysis of Schizosaccharomyces pombe mutants that are defective in septum formation and cytokinesis has identified the product of the cdc15 gene as a key element in formation of a division septum. S. pombe cells lacking cdc15p function cannot assemble a functional medial ring, and do not make a division septum. cdc15 mRNA accumulates periodically during the cell cycle, peaking after entry into mitosis, and increased expression of the gene in G2-arrested cells can promote F-actin ring formation. Here, we have investigated the effects of mutations that block cell division upon the expression of cdc15 in synchronised cell populations, and analysed the expression of cdc15 when septum formation is induced by ectopic activation of the septation signalling network. We concluded the following: (i) the septation signalling network genes are not required for periodic accumulation of cdc15 mRNA; (ii) induction of septum formation in G2-arrested cells by activation of the septation signalling network does not result in accumulation of cdc15 mRNA, which is therefore not a prerequisite for septum formation; (iii) failure to turn off septum formation at the end of mitosis results in continued expression of cdc15; and (iv) periodic accumulation of cdc15 mRNA is mediated by a 97 bp region 5' to the mRNA start site.

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.

Fièvre à répétition chez l'enfant: penser au syndrome de PFAPA [Periodic fever in children: keep in mind the PFAPA syndrome]

Les maladies autoinflammatoires font partie du diagnostic différentiel de l'état fébrile à répétition chez l’enfant. Ces maladies sont caractérisées par des poussées inflammatoires sans cause évidente. Certaines de ces maladies, comme la Fièvre méditerranéenne familiale, ont une origine génétique et nécessitent un traitement régulier pour éviter des conséquences graves à long terme. Le syndrome de PFAPA est la plus fréquente des fièvres récurrentes et son diagnostic se base sur des critères diagnostiques peu précis. Son traitement reste controversé. La prednisone en dose unique permet d'interrompre la poussée et l'amygdalectomie peut induire une rémission dans une majorité des cas. The autoinflammatory diseases should be considered in the differential diagnosis of recurrent fever in childhood. These diseases are characterized by inflammatory episodes without an evident cause. Some of these diseases, like the Familial Mediterranean Fever, have a genetic origin and need a chronic treatment to avoid severe complications on the long term. PFAPA syndrome is the most frequent cause of recurrent fever and is diagnosed based on unspecific criteria. The treatment is still controversial. One dose of Prednisone is able to interrupt the flare and tonsillectomy may induce a remission in the majority of the cases

Effective stiffening of DNA due to nematic ordering causes DNA molecules packed in phage capsids to preferentially form torus knots.

Observation that DNA molecules in bacteriophage capsids preferentially form torus type of knots provided a sensitive gauge to evaluate various models of DNA arrangement in phage heads. Only models resulting in a preponderance of torus knots could be considered as close to reality. Recent studies revealed that experimentally observed enrichment of torus knots can be qualitatively reproduced in numerical simulations that include a potential inducing nematic arrangement of tightly packed DNA molecules within phage capsids. Here, we investigate what aspects of the nematic arrangement are crucial for inducing formation of torus knots. Our results indicate that the effective stiffening of DNA by the nematic arrangement not only promotes knotting in general but is also the decisive factor in promoting formation of DNA torus knots in phage capsids.

Seizure detection with automated EEG analysis: a validation study focusing on periodic patterns.

OBJECTIVE: To evaluate an automated seizure detection (ASD) algorithm in EEGs with periodic and other challenging patterns. METHODS: Selected EEGs recorded in patients over 1year old were classified into four groups: A. Periodic lateralized epileptiform discharges (PLEDs) with intermixed electrical seizures. B. PLEDs without seizures. C. Electrical seizures and no PLEDs. D. No PLEDs or seizures. Recordings were analyzed by the Persyst P12 software, and compared to the raw EEG, interpreted by two experienced neurophysiologists; Positive percent agreement (PPA) and false-positive rates/hour (FPR) were calculated. RESULTS: We assessed 98 recordings (Group A=21 patients; B=29, C=17, D=31). Total duration was 82.7h (median: 1h); containing 268 seizures. The software detected 204 (=76.1%) seizures; all ictal events were captured in 29/38 (76.3%) patients; in only in 3 (7.7%) no seizures were detected. Median PPA was 100% (range 0-100; interquartile range 50-100), and the median FPR 0/h (range 0-75.8; interquartile range 0-4.5); however, lower performances were seen in the groups containing periodic discharges. CONCLUSION: This analysis provides data regarding the yield of the ASD in a particularly difficult subset of EEG recordings, showing that periodic discharges may bias the results. SIGNIFICANCE: Ongoing refinements in this technique might enhance its utility and lead to a more extensive application.

International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients.

OBJECTIVES: The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. METHODS: We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. RESULTS: Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. CONCLUSION: We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.

Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) in comatose survivors of cardiac arrest: Characteristics and prognostic value.

OBJECTIVES: To analyze the prevalence of stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) in patients with coma after cardiac arrest (CA) and therapeutic hypothermia (TH) and to examine their potential association with outcome. METHODS: We studied our prospective cohort of adult survivors of CA treated with TH, assessing SIRPIDs occurrence and their association with 3-month outcome. Only univariated analyses were performed. RESULTS: 105 patients with coma after CA who underwent electroencephalogram (EEG) during TH and normothermia (NT) were studied. Fifty-nine patients (56%) survived, and 48 (46%) had good neurological recovery. The prevalence of SIRPIDs was 13.3% (14/105 patients), of whom 6 occurred during TH (all died), and 8 in NT (3 survived, 1 with good neurological outcome); none had SIRPIDs at both time-points. SIRPIDs were associated with discontinuous or non-reactive EEG background and were a robustly related to poor neurological outcome (p<0.001). CONCLUSION: This small series provides preliminary univariate evidence that in patients with coma after CA, SIRPIDs are associated with poor outcome, particularly when occurring during in therapeutic hypothermia. However, survival with good neurological recovery may be observed when SIRPIDs arise in the post-rewarming normothermic phase. SIGNIFICANCE: This study provides clinicians with new information regarding the SIRPIDs prognostic role in patients with coma after cardiac arrest.

A partial ordering of knots and links through diagrammatic unknotting

In this paper we de. ne a partial ordering of knots and links using a special property derived from their minimal diagrams. A link K' is called a predecessor of a link K if Cr(K') < Cr(K) and a diagram of K' can be obtained from a minimal diagram D of K by a single crossing change. In such a case, we say that K' < K. We investigate the sets of links that can be obtained by single crossing changes over all minimal diagrams of a given link. We show that these sets are specific for different links and permit partial ordering of all links. Some interesting results are presented and many questions are raised.

Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.