Average Episode Duration Research Articles

Does Snoring Change the Palatal Sensation?

Objective: Patients with obstructive sleep apnea syndrome (OSAS) have impaired responses in inspiratory resistive loading during sleep. This may be due, in part, to a change in the upper airway sensation. Therefore, we hypothesized that patients with OSAS had diminished upper airway sensation due to snoring. Method: Case-control study. Conducted: from May 2011 to March 2012. Participants were selected based on clinical evaluation and polysomnography. Two-point discrimination was measured with modified calipers in the tongue and soft palate.Independent variables: snoring time components. Results: Comparing polysomnography, patients with impairment of their palatal sensory input in 2-point discrimination had longer longest-snoring episodes than those with normal sensation ( P =.010). And patients with decreased sensory input in 2-point discrimination had longer average snoring episode duration than those with normal sensory input ( P = .043). However, the total snoring time and relative snoring time also increased in patients with sensory impairment, but statistical significance was not found ( P = .20, P = .24 respectively). Conclusion: Two-point discrimination in the anterior tongue and soft palate was impaired in patients with OSAS. We speculate that this impairment might be due to a primary sensory function abnormality or secondary to nerve damage and/or hypoxemia caused by snoring. Further studies after treatment of OSAS are needed.

Study of sleep in a walrus

Several behavioral and physiological adaptations have been developed in evolution of Pinnipeds allowing them to sleep both on land and in water. To date sleep has been examined in detail in eared and true seals (the families of Otariidae and Phocidae). The aim of this study was to examine sleep in another semiaquatic mammal - the walrus, which is the only extant representative of the family Odobenidae. Slow wave and paradoxical sleep (SWS and PS) in the examined walrus (2 year old female, weight 130 kg) averaged 19.4 ± 2.0 and 6.9 ± 1.1% of 24-h when on land, and 20.5 ± 0.8% of 24-h and 1.1 ± 0.6% when in water, respectively. The average duration of PS episode was 6.4 ± 0.6 min (maximum 23 min) when on land and 1.8 ± 0.1 min (maximum 3.3 min) when in water. In water, sleep occurred predominantly while the walrus submerged and lay on the bottom of the pool (89% of total sleep time). The walrus usually woke up while emerging to the surface for breathing. Most often EEG slow waves developed synchronously in both cortical hemispheres (90% of SWS time when on land and 97% when in water). Short episodes of interhemispheric EEG asymmetry usually coincided with brief opening of one eye. The pattern of sleep in the walrus was similar to the pattern of sleep in the Otariidae seals while on land (predominantly bilateral SWS, accompanied by regular breathing) and to the pattern of sleep in the Phocidae while in water (sleep during apneas both in depth and at the surface, interrupted by brief arousal when emerging for breathing).

Optogenetic disruption of sleep continuity impairs memory consolidation

Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate a single sleep feature while maintaining the others constant. Here, we introduce the use of optogenetics to investigate the role of sleep continuity in memory consolidation. We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity. Fragmenting sleep after the learning phase of the novel object recognition (NOR) task significantly decreased the performance of mice on the subsequent day, but memory was unaffected if the average duration of sleep episodes was maintained at 62-73% of normal. These findings demonstrate the use of optogenetic activation of arousal-related nuclei as a way to systematically manipulate a specific feature of sleep. We conclude that regardless of the total amount of sleep or sleep intensity, a minimal unit of uninterrupted sleep is crucial for memory consolidation.

Vestibular disorders among adults in a tertiary hospital in Lagos, Nigeria

Dizziness is not an uncommon complaint in the Otolaryngological clinics among other symptoms. To a large number of practitioners, the treatment of dizziness remains the same irrespective of the etiology, i.e., anti-vertiginous drugs. The objective of this study was to document the evaluation, causes and treatment of vestibular disorders among our patients. The design includes descriptive prospective study conducted in the Oto-rhino-laryngology and Orthopedic Clinics of Lagos University Teaching Hospital, Lagos and Nigerian Army Audiological Centre, 68 Nigerian Army Reference Hospital, Yaba, Lagos, Nigeria. Adult patients referred to the audiology clinic for dizziness had detailed history obtained by using structured questionnaire. General physical and neuro-otological examinations were done. Clinical diagnoses were made on standardized criteria. The patients had hearing evaluation, videonystagmography (VNG) evaluation using infrared videonystagmography system. X-ray of the cervical spine and computerized tomogram scan of internal auditory meatus and brain when indicated were done. A total of 102 patients were seen with age range between 21 and 90 years. Thirty patients (29.4%) recorded average duration of episode of vertiginous attacks in seconds, 69 (67.6%) recorded within minutes to hours and 3 (2.9%) with no definite pattern. Clinical signs on neuro-otological examination were elicited on 39 (38.2%) of the patients while on VNG the vestibular subtest mainly caloric test was abnormal unilaterally and bilaterally in 47 (46.1%) while with the oculomotor subtests, smooth pursuit tests were abnormal in 5 (6.9%), saccade tests were abnormal in 8 (7.8%) and OPK were abnormal in 9 (8.8%). Peripheral vestibular disorders are common of which benign paroxysmal positional vertigo (BPPV) was seen in 29 (28.4%), Meniere's disease in 22 (21.6%), recurrent vestibulopathy in 20 (19.6%), cervical vertigo in 18 (17.6%), psychogenic vertigo in 2 (2%), vestibular schwannoma, barotraumas and drug-induced vertigo in 1 (1%), respectively, central vestibular disorders of vascular origin 2 (2%), vertebrobasilar insufficiency in 1 (1%), post-traumatic vertigo in 3 (3%) and unknown in 2 (2%). In conclusion, peripheral vestibular disorders are common of which BPPV is the most prevalent. Pre-referral anti-vertiginous medication is common among general practitioners. The practising ORL/Head neck surgeon and orthopedic surgeons must be conversant with the tools of diagnosis, differential diagnosis and treatment.

Subsyndromal states in bipolar disorder

Background:Despite adequate treatment, patients with bipolar disorder suffer from subsyndromal symptoms. This study has been done to see the association of subsyndromal symptoms with age of onset, duration of illness, duration of episodes, and number of episodes.Aims:To know the prevalence of subsyndromal symptoms and their relationship with age of onset, total duration of illness, number of episodes, and duration of episodes in patients with bipolar disorder in remission.Materials and Methods:The study was cross sectional and hospital based. One hundred patients, aged between 18 and 65 years, diagnosed as bipolar disorder according to Research Diagnostic Criteria of ICD-10, and with good compliance with the prophylactic medications, score of ≤5 on Beck’s Mania Rating Scale (BMRS) and score ≤8 on Hamilton Depression Rating Scale (HDRS) were recruited by the purposive sampling method. Descriptive statistics were used to describe various sample characteristics. Group differences for categorical variables were examined with the chi-square test, whereas an independent ‘t’ test was used for continuous variables.Results:The most common manic symptom was a decrease in sleep (49%), followed by an increase in verbal activity (39%), hostility (37%), and increase in motor activity (33.33%). The subsyndromal manic group had a lower age of onset (58.8%), males (82.4%), unemployed (23.5%), educated (80.4%). There was no significant difference between with and without subsyndromal mania groups with respect to age, age of onset, duration of illness, number of episode, and average duration of episode.Conclusion:Subsyndromal manic symptoms are prevalent and have no relationship with current age, age of onset of illness, duration of illness, number of episode, and average duration of illness in patient with bipolar disorder in remission.

Small platform sleep deprivation selectively increases the average duration of rapid eye movement sleep episodes during sleep rebound

The single platform-on-water (flower pot) method is extensively used for depriving rapid eye movement sleep (REMS). Detailed comparison of sleep–wake architecture, recorded during the rebound period after spending three days on either a small or large platform, could separate the effects of REMS deficit from other stress factors caused by the procedure. A further aim of the study was to find the most characteristic REMS parameter of the rebound originating from REMS deficit. Rats were kept on a small or large platform for 72 h. Their fronto-parietal electroencephalogram, electromyogram and motility were recorded during the 24 h rebound at the beginning of the passive phase. A similar period of a home cage group was also recorded. The most typical differences between the two rebound groups were the increased cumulative time and longer average duration of REMS episodes without significant change in the number of these episodes of the small platform animals during the passive phase. Results obtained by cosinor analysis were in accordance with the findings above. Since we did not find any difference in the average duration of REMS episodes comparing the large platform rebound group and the home cage group, we concluded that the increased mean duration of REMS episodes is a selective marker for the rebound caused by small platform sleep deprivation, while other changes in sleep architecture may be the consequence of stress and also some sleep deficit.

An 8-year longitudinal study of the natural history of threshold, subthreshold, and partial eating disorders from a community sample of adolescents.

The authors examined the natural history of threshold, subthreshold, and partial eating disorders in a community sample of 496 adolescent girls who completed annual diagnostic interviews over an 8-year period. Lifetime prevalence by age 20 years was 0.6% and 0.6% for threshold and subthreshold anorexia nervosa (AN), 1.6% and 6.1% for threshold and subthreshold bulimia nervosa (BN), 1.0% and 4.6% for threshold and subthreshold binge-eating disorder (BED), and 4.4% for purging disorder (PD). Overall, 12% of adolescents experienced some form of eating disorder. Subthreshold BN and BED and threshold PD were associated with elevated treatment, impairment, and distress. Peak age of onset was 17-18 years for BN and BED and 18-20 years for PD. Average episode duration in months was 3.9 for BN and BED and 5.1 for PD. One-year recovery rates ranged from 91% to 96%. Relapse rates were 41% for BN, 33% for BED, and 5% for PD. For BN and BED, subthreshold cases often progressed to threshold cases and diagnostic crossover was most likely for these disorders. Results suggest that subthreshold eating disorders are more prevalent than threshold eating disorders and are associated with marked impairment.

Under restrictive conditions, can the widths of linear enamel hypoplasias be used as relative indicators of stress episode duration?

Linear enamel hypoplasia (LEH), a type of enamel defect reflecting nonspecific physiological stress, has traditionally been used by bioarchaeologists to assess human health. Initially, measurements of defect width were used to estimate the duration of stress episodes. More recently, methods of counting within-defect perikymata (enamel growth increments) were developed to more accurately assess duration. Because perikymata are often not continuously visible within defects, while widths can usually be measured, the primary purpose of this article was to determine if, under restrictive conditions, the widths of LEH defects might be used as relative indicators of stress episode duration. Using a set of dental replicas from the prehistoric Irene Mound (1150-1400 A.D.), this study also investigated potential sources of variation in defect widths and how often defect widths could be measured and within-defect perikymata counted. Of 120 defects, only 47 contained both measurable defect widths and total within-defect perikymata, while 79 had measurable defect widths. Regression analysis revealed that, for these 47 defects, defect widths were more strongly related to the total number of within-defect perikymata than they were to crown region or tooth type. Although wide prediction intervals indicated that a defect's width could not be used to predict the number of within-defect perikymata for an individual, narrower confidence intervals associated with hypothetical mean population widths suggested that mean defect widths might be used to rank populations in terms of relative average stress episode duration.

Prolonged Dry Episodes over the Conterminous United States: New Tendencies Emerging during the Last 40 Years

AbstractA disproportionate increase in precipitation coming from intense rain events, in the situation of general warming (thus, an extension of the vegetation period with intensive transpiration), and an insignificant change in total precipitation could lead to an increase in the frequency of a potentially serious type of extreme events: prolonged periods without precipitation (even when the mean seasonal rainfall totals increase). This paper investigates whether this development is already occurring during the past several decades over the conterminous United States, for the same period when changes in frequency of intense precipitation events are being observed. Lengthy strings of “dry” days without sizeable (>1.0 mm) precipitation were assessed only during the warm season (defined as a period when mean daily temperature is above the 5°C threshold) when water is intensively used for transpiration and prolonged periods without sizable rainfall represent a hazard for terrestrial ecosystem’s health and agriculture. During the past four decades, the mean duration of prolonged dry episodes (1 month or longer in the eastern United States and 2 months or longer in the southwestern United States) has significantly increased. As a consequence the return period of 1-month-long dry episodes over the eastern United States has reduced more than twofold from 15 to 6–7 yr. The longer average duration of dry episodes has occurred during a relatively wet period across the country but is not observed over the northwestern United States.

Lactoferrin Glu561Asp polymorphism is associated with susceptibility to herpes simplex keratitis

Lactoferrin plays an important role in the defense against infections, including herpes simplex virus (HSV) keratitis. We studied the impact of three single nucleotide polymorphisms in the human lactoferrin gene on the susceptibility to HSV infections of the eye and the severity of such infections. Lactoferrin gene polymorphisms were determined by PCR combined with restriction fragment length analysis in 105 HSV keratitis patients and 145 control subjects. Bilateral tear samples were harvested from 50 patients and 40 healthy controls and tear lactoferrin concentrations were determined by ELISA. Patients' records were used to acquire information about the severity of the HSV keratitis. The frequencies of the Glu561Asp polymorphism, but not those of the Ala11Thr and Lys29Arg polymorphisms, differed significantly between patients and control subjects with an under-representation of the Asp561 allele in the patient group. Furthermore, the values for best corrected visual acuity, frequency of recurrences since onset, and average duration of clinical episodes did not differ among patients with various lactoferrin genotypes. In addition, tear lactoferrin concentrations were the same in patients with HSV keratitis and healthy controls and also did not differ among patients with various lactoferrin genotypes. Lactoferrin Glu561Asp polymorphism is associated with the susceptibility to HSV keratitis with a protective role for lactoferrin variants comprising Asp561. However, no beneficial effects of this lactoferrin variant on the clinical outcome of ocular HSV keratitis were noted.

The effects of atropine on changes in the sleep patterns induced by psychological stress in rats

The present study was designed to investigate the acute effects of psychological stress on the sleep patterns of rats and the potential mechanisms underlying these effects. Psychological stress was induced using a communication box. In a preliminary study, sleep recording was performed for 6 h immediately after 1-h stress in rats. The results showed that psychological stress significantly enhanced the total amount of rapid eye movement (REM) sleep by prolonging the average duration of REM sleep episodes during first 3 h of sleep, whereas the total amount of non-rapid eye movement sleep was not influenced. In a second study, three doses of atropine (3, 10, or 30 nmol) were intracerebroventricularly microinjected into the rats. Total REM sleep was inhibited by the highest dose of atropine during the first 3 h of sleep in the stressed group but not in the control group; the inhibition of total REM sleep was due to a reduction in the average duration of REM sleep episodes. These results suggest that the increase in total REM sleep induced by stress was related to the activation of cholinergic neurons. In addition, plasma corticosterone—an index of hypothalamic–pituitary–adrenal (HPA) axis activity in response to stress—was examined after psychological stress. The concentration of corticosterone did not change significantly. Therefore, the abnormal sleep patterns could not be simply attributed to the HPA axis. These results indicate that the changes in sleep patterns induced by stress were related to cholinergic neurons, but not the HPA axis.

Estimating the Longitudinal Prevalence of Diarrhea and Other Episodic Diseases

Longitudinal prevalence (ie, the proportion of time with the disease) is used to describe morbidity from diarrhea and other episodic conditions. The aim of this analysis was to compare estimates of longitudinal prevalence based on intermittent sampling at regular intervals with 24- or 48-hour recall, with estimates based on continuous surveillance. Based on 2 real datasets from Brazil and Guatemala, we developed a simulated dataset representing the diarrhea morbidity of 10,000 individuals followed over 365 days. Both the model and the real datasets showed that the standard deviation of the longitudinal prevalence increases with decreasing numbers of days sampled, so that a study sampling only a fraction of days would require a larger sample size. However, due to the correlation of diarrhea between consecutive days, sampling at 7- to 14-day intervals results in relatively small loss of precision and power compared with daily morbidity records, especially when the average diarrheal episode is long. A study based on morbidity data for every seventh day may require only a 5%-24% larger sample size than a study with daily records, depending on the average duration of episodes. Using a recall period of 48 hours instead of 24 hours increases power if the average episode is short. The results question the necessity of continuous surveillance to estimate longitudinal prevalence. In addition to savings in cost and staff time, intermittent sampling of morbidity may improve validity by minimizing recall error and reducing the influence of surveillance on participants' behavior.

Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness

Sleep fragmentation, a feature of sleep apnea as well as other sleep and medical/psychiatric disorders, is thought to lead to excessive daytime sleepiness. A rodent model of sleep fragmentation was developed (termed sleep interruption, SI), where rats were awakened every 2 min by the movement of an automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats exposed to 24 h of SI resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM) sleep time was greatly reduced, non-rapid eye movement (NREM) sleep episode duration was reduced (from 2 min, 5 s baseline to 58 s during SI), whereas the total amount of NREM sleep time per 24 h approached basal levels. Both 6 and 24 h of SI made rats more sleepy, as indicated by a reduced latency to fall asleep upon SI termination. Electrographic measures in the recovery sleep period following either 6 or 24 h of SI also indicated an elevation of homeostatic sleep drive; specifically, the average NREM episode duration increased (e.g. for 24 h SI, from 2 min, 5 s baseline to 3 min, 19 s following SI), as did the NREM delta power during recovery sleep. Basal forebrain (BF) levels of extracellular adenosine (AD) were also measured with microdialysis sample collection and high performance liquid chromatography detection, as previous work suggests that increasing concentrations of BF AD are related to sleepiness. BF AD levels were significantly elevated during SI, peaking at 220% of baseline during 30 h of SI exposure. These combined findings imply an elevation of the homeostatic sleep drive following either 6 or 24 h of SI, and BF AD levels appear to correlate more with sleepiness than with the cumulative amount of prior wakefulness, since total NREM sleep time declined only slightly. SI may be partially responsible for the symptom of daytime sleepiness observed in a number of clinical disorders, and this may be mediated by mechanisms involving BF AD.

Cartel Stability: An Empirical Analysis

Using the data on 238 cartelized markets we evaluate econometrically the impact of cartel characteristics as well the market and legal environment of cartel operation on cartel stability. The latter is measured as the expected number of repeated attempts to form a cartel in the same product market. We analyze the behavior of guilty (sanctioned) cartels relative to legal cartels. We find that global cartels are less stable than local cartels. Cartels operating in the countries with developed antitrust law are more stable than cartels operating in the countries without similar regulation. As antitrust law regimes become stricter, sanctioned cartels become less stable. If the average duration of cartel episode is relatively short, the cartel is more likely to make another attempt to collude. If a cartel manages to impose a relatively high level of overcharge, the cartel is less likely to repeat collusive conduct.

Connection between efficacy of atrial fibrillation preventive pacing algorithms and atrial pacing ratio

The purpose of the study was to evaluate efficacy of main pacing algorithms for prevention of atrial fibrillation (AF) atrial pacing ratio. Methods In 17 patients (13 male, 4 female), mean age 67±6,4 years with conventional pacing indications and documented paroxysmal AF implantation of DDDRP pacemakers (11 ELA, 6 Vitatron) were performed. AF prevention algorithms were activated on 3-7th day after operation and were adopted if necessary every follow-up visit according individual mechanisms of AF onset. Each patient was programmed and evaluated at least every 3 months during 11,5±6,8 month period. We compared quantity of AF episodes/daily, AF episode duration, total AF burden (% of storage period), share of paced atrial rhythm in early (first 6 months after implantation – phase A) and late postoperational period (6-12th month after implantation – phase B). Results In 6 cases during first 3 months radiofrequency AV junction ablation was performed because persistent AF paroxysms with poor tolerability. The number of AF episodes/daily during first 3-6 months did not differ significantly between both groups (3,9 ± 5,8 vs. 2,8 ± 2,3, p=0,25) as not the atrial pacing ratio (58,6 ± 39,3% vs. 63,7 ± 25,1%, p=0,13). Average AF episode duration (171,6±99,3 min vs.105,2±74,4 min, p<0.05) and total AF burden (23,7 ± 19,0% vs. 9,2 ± 14,7%, p<0,01) significantly reduced in phase B after initial adaptation of AF-prevent algorithms. Symptomatic improvement was reported by all patients, no patient experienced pacemaker dysfunction. Conclusion AF episode duration and total AF-burden can be significantly reduced by using preventive pacing algorithms in patients with paroxysmal AF as a result of overdrive pacing. However, increase of atrial pacing ratio hardly could be a criteria of properly selected AF-prevent algorithm. Therefore, further studies to determine precise recommendations for implementation of AF-prevent algorithms needed.

Features of isolated sleep paralysis among Nigerians

There is paucity of studies on isolated sleep paralysis (ISP). To explore the relationship of variables for ISP sufferers, and clarify factors predictive of ISP health behaviour (IHB--doing something to prevent further attacks). Cross-sectional study. General population. 24-item ISP questionnaire completed by respondents. One hundred and ten (38.2%m, aged 30.9 years). Mean ISP frequency in the lifetime, past year and past month, were respectively, 6.7, 2.02, and 0.5; average duration of episodes was four minutes, and 63.6% experienced it while awakening from sleep. Using ICSD criteria, 2.7% had severe experience (i.e. at least once per week), 18.2% moderately severe (once per month) and 75.5% mildly severe (less than once per month), with no significant demographic associations. 56.4% were afraid of the experience, 76.4% had little/no worries that something was seriously wrong with their bodies; 39.1% cited supernatural causes, 35.5% cited physiological/psychosocial causes; and 44.5% described a hallucinatory experience. 1.8% took medical measures, and 7.3% consulted a faith healer; 44.5% resorted to prayers and 41.8% did nothing to prevent further attacks. The primary determinant of IHB was being afraid of ISP. These findings have public mental health education, treatment and research implications.

Costs of lower-extremity ulcers among patients with diabetes.

The objective of this study was to characterize health care costs associated with diabetic lower-extremity ulcers. Adult patients with diabetes who had a lower-extremity ulcer episode during 2000 and 2001 were identified using claims data. Ulcer-related direct health care costs were computed for each episode. Episodes were stratified according to severity level based on the Wagner classification. A total of 2,253 patients were identified. The mean age was 68.9 years, and 59% of the patients were male. The average episode duration was 87.3 +/- 82.8 days. Total ulcer-related costs averaged 13,179 dollars per episode and increased with severity level, ranging from 1,892 dollars (level 1) to 27,721 dollars (level 4/5). Inpatient hospital charges accounted for 77% (10,188 dollars) of the overall cost, indicating that hospitalization was a major cost driver. Total ulcer-related costs were significantly higher for patients <65 years of age compared with those of older patients (16,390 dollars vs. 11,925 dollars, P = 0.02) and for patients with inadequate vascular status compared with patients with adequate vascular status (23,372 dollars vs. 5,218 dollars, P < 0.0001). Patients who progressed to a higher severity level also had significantly higher ulcer-related costs compared with patients who did not progress (20,136 dollars vs. 3,063 dollars, P < 0.0001). The high costs of treating diabetic lower-extremity ulcers emphasize the value of intensive outpatient interventions designed to prevent ulcer progression.

Sick leave certification: an unwelcome administrative burden for the family doctor? The role of sickness certification in Maltese family practice

Introduction: In Malta, sickness certificates are needed from the first day of illness, and are issued by family doctors (FDs) either employed in the government primary healthcare system, or self-employed in private practice, or employed directly by an employer for this purpose alone. Patients visiting self-employed FDs pay directly, and are not reimbursed unless privately insured. We aimed to contribute to die discussion on die impact of sickness certification in family practice by studying the phenomenon using electronic data from an electronic patient record (EPR) used by self-employed FDs. We used this data to study the frequency of sickness certification and the relationship between the patient's reason for encounter, with or without a formal request for a certificate, and the doctor's diagnosis and certification practice.Methods: We used data collected by FDs in day-to-day private family practice using an episode-oriented EPR. The EPR database included all encounters in all episodes of care over a period of one year (1 January to 31 December 2001) documented by ten self-employed FDs, comprehensively coded with ICPC-2-E (Electronic Version of the International Classification of Primary Care, version 2).Results: The EPR database documented care for 7497 patients (45.4% male) over one year. During 15,781 encounters, sickness certificates were issued in 11.3% of 16,319 episodes of care. 5.7% of the reasons for encounter presented by the patient in new episodes were requests for administrative procedures, and this request was made in 8.2% of all new episodes of care.Conclusion: The distribution of morbidity seen by the FDs appeared to be very wide, with a dominance of acute respiratory, gastrointestinal and musculoskeletal symptoms and diagnoses, and the role of sickness certification was quite important. The frequency of sick leave certification in Malta is comparable with that in other European countries, but the average duration of episodes is shorter. Just over 11% of private FD encounters involve issuing a sickness certificate. The high proportion of reasons for encounter formulated as a request for a sickness certificate suggests that the active role of FDs in this form of social security in the Maltese population has supported the local development of family practice.

Mutation of a New Gene Encoding a Putative Pyrin-Like Protein Causes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome

Purpose of the Study. To identify the genes for familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS).Study Population. Three families with FCAS and 1 family with MWS.Methods. Genomic DNA isolation, identification of coding region, DNA sequencing, and mutation detection. Protein prediction programs were also performed.Results. Four distinct mutations of the CIAS1 Gene on chromosome 1q44 were identified. The gene encodes a newly identified protein called cryopyrin.Conclusion. Mutations of the CIAS1 Gene encoding cryopyrin cause at least two distinct but similar cold-sensitive diseases, including FCAS and MWS.Reviewers’ Comments. This exciting discovery has led to the identification of a new protein, aptly named “cryopryin,” that links cold temperature exposure to inflammation. In this report, mutations of the cryopyrin gene were identified in family members with 2 rare autosomal dominant conditions that are “autoinflammatory” disorders (ie, conditions with recurrent inflammatory symptoms in the absence of autoantibodies): FCAS and MWS. Recently, FCAS—also known as familial cold urticaria and familial polymorphous cold eruption—has been well-described by the same authors. The FCAS clinical picture includes: skin rash (100%), arthralgia (96%), fever (93%), conjunctivitis (84%), disease onset in the first 6 months of life (95%), an average time delay between cold exposure and the onset of symptoms of 2.5 hours, and an average episode duration of 12 hours (Hoffman HM, et al. J Allergy Clin Immunol. 2001;108:615–620). In contrast, MWS leads to progressive sensorineural deafness, amyloidosis of the kidneys and other organs, fevers, chills, rigors, malaise, and chronic recurrent urticaria. The reason for the 2 distinct clinical entities associated with mutations in the same gene still need to be explored. For more discussion, see a brief editorial entitled “A fever gene comes in from the cold” by Kastner and O’Shea on pages 241–242 of the same issue.

Learning and sleep: the sequential hypothesis.

During the last 30 years, paradoxical sleep (PS) has been generally considered as the only type of sleep involved in memory processing, mainly for the consistent increase of PS episodes in laboratory animals learning a relatively complex task, and for the retention deficits induced by post-training PS deprivation. The vicissitudes of this idea, examined in detail by several laboratories, have been critically presented in a number of review articles However, according to a more comprehensive unitary proposal (the sequential hypothesis), memory processing during sleep does require the initial participation of slow-wave sleep (SS) in addition to the subsequent involvement of PS. The evidence supporting this hypothesis, largely derived from experiments concerning rats trained for a two-way active avoidance task, is reviewed here in some detail. Recent studies of human sleep are in full agreement with this view. In the rat, the main effect of learning on post-training SS consists in the selective increment in the average duration of SS episodes initiating different types of sleep sequences. Notably, following training for a two-way active avoidance task, the occurrence of this effect in sleep sequences including transition sleep (TS), such as SS-->TS-->W and SS-->TS-->PS, appears related to the processing of memories of the novel avoidance response. Conversely, the occurrence of the same effect in sleep sequences lacking TS may reflect the processing of memories of innate responses (escapes and freezings). Memories of innate and novel responses are assumed to engage in a dynamic competitive interaction to attain control of waking behaviour. Interestingly, in baseline sleep, variables of SS-->TS-->W and SS-->TS-->PS sequences, such as the average duration of SS, TS, and PS episodes, have proved to be good indices of the capacity to learn, as shown by their strong correlations with the number of avoidances scored by rats the following day. Comparable correlations have not been displayed by variables of baseline SS-->W and SS-->PS sequences.