Family study of epilepsy in first degree relatives: data from the Italian Episcreen Study

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Cannabidiol modulates phosphorylated rpS6 signalling in a zebrafish model of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene. CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2-/- larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2-/- larval brain. Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC

ОСОБЛИВОСТІ ЕМОЦІЙНО-ПОВЕДІНКОВИХ РЕАКЦІЙ У ЩУРІВ ПРИ МОДЕЛЮВАННІ В НИХ СИНДРОМУ АПНОЕ СНУ

Summary. Obstructive sleep apnea-hypopnea syndrome (OSAHS) – a pathological condition of pulmonary ventilation in patients over 10 seconds; during 7 hours of sleep apnea-hypopnea is registered at least 30 times. It is caused by periodic obstruction of the upper respiratory tract at the level of the throat; at the same time against the background of preservation of respiratory efforts the pulmonary ventilation is suspended and oxygen saturation of blood decreases; patients experience gross sleep fragmentation and excessive daytime sleepiness. Patients have a significant deterioration in quality of life due to insomnia disorders, and develop a symptom complex of organic disorders. For a deeper study of the pathogenetic mechanisms of OSAHS, it is advisable to use experimental models on small laboratory animals. The aim of the study – to evaluate the features of emotional and behavioral reactions in rats when simulating their sleep apnea syndrome. Materials and Methods. The study was performed on 42 white outbred male rats that were on a regular vivarium diet. To exclude accidental influences, all animals were in the same conditions and entered the experiment at the same time. Nonlinear white adult male rats weighing (200±10) g  were taken for the experiment in order to eliminate the fluctuations of the hormonal background. The animals were divided into 3 groups: I – rats which under barbiturate anesthesia were simulated obstructive sleep apnea (21 rats), II – rats, which underwent barbiturate anesthesia (14 rats), III – intact animals (7 rats). The animals were provided with medicated sleep by anesthesia. 1 % thiopental sodium solution was used for this purpose. Anesthetic at a dose of 60 mg/kg was injected intraperitoneally into the hypogastric area. Animals of the intact group received an intraperitoneally equivalent amount of isotonic NaCl solution. The physiological activity of rats was studied by the Buresh test in the open field. The features of emotional and behavioral reactions in animals, which simulated the syndrome of obstructive sleep apnea-hypopnea were investigated. To do this, a device was constructed which, with the help of an electromagnetic shutter, causes the two straps to be closed in time, between which a latex thin-walled coupling is fixed, worn on the muzzles of animals, the proximal part of which is close to the scalp. The animals were in a medicated sleep. The study was conducted on 4, 12 and 18 days. Results. During the simulation of inspiratory apnea, their intrapleural pressure increased 5–6 times. We studied the emotional and behavioral responses of 42 rats on the test "open field" with an interval of 3 days, a total duration of 18 days. Deterioration of values of horizontal and vertical activity and indicators of vegetative balance on the background of anesthesia and, especially, in the simulation of obstructive sleep apnea syndrome, which showed their ability to impair adaptation, in contrast to intact animals. Conclusions. For in-depth study of the phenomenon of obstructive sleep apnea-hypopnea, it is advisable to apply the proposed experimental model of inspiratory overlap of the oral and nasal lumens of animals for (2.2±0.2) second during each minute of sleep during anesthesia. When modeling obstructive sleep apnea-hypopnea in rats there are functional changes – a decrease in emotional and behavioral responses and autonomic balance, which indicates a pronounced violation of adaptive mechanisms.Резюме. Синдром обструктивного апное-гіпопное під час сну (СОАГС) – патологічний стан зупинки вентиляції легенів у хворих понад 10 с; при цьому протягом 7- годинного сну апное-гіпопное реєструється не менше 30 разів. Він зумовлений періодичною обструкцією верхніх дихальних шляхів на рівні горла; при цьому на тлі збереження дихальних зусиль призупиняється легенева вентиляція та понижується насиченість крові киснем; у пацієнтів виникає груба фрагментація сну та надмірна денна сонливість. У хворих спостерігається суттєве погіршення якості життя, зумовлене інсомнічними розладами, та розвивається при цьому симптомокомплекс органічних порушень. Для глибшого вивчення патогенетичних механізмів СОАГС доцільно використовувати експериментальні моделі на дрібних лабораторних тваринах. Мета дослідження – оцінити особливості емоційно-поведінкових реакцій у щурів при моделюванні в них синдрому апное сну. Матеріали і методи. Дослідження проведено на 42-х білих безпородних щурах-самцях, які перебували на звичайному харчовому раціоні віварію. Для виключення випадкових впливів усі тварини перебували в однакових умовах і брали їх для досліду в один і той же час. З метою усунення коливань гормонального фону для експерименту брали нелінійних білих статевозрілих щурів-самців, маса яких була (200±10) г. Тварин поділили на 3 групи: першу – щури, у яких під барбітуровим наркозом моделювали синдром обструктивного апное-гіпопное сну (21 тварина), друга – щури, яким проводили барбітуровий наркоз (14 тварин), третя – інтактні тварини (7 щурів). Забезпечували тваринам медикаментозний сон, вводячи їх у наркоз. Для цього використовували 1% розчин натрію тіопенталу. Анестетик у дозі 60 мг/кг вводили внутрішньочеревно у ділянку гіпогастрію. Тварини інтактної групи отримували внутрішньочеревно еквівалентну кількість ізотонічного розчину NaCl. Проводили дослідження фізіологічної активності щурів за тестом Буреша у відкритому полі. Досліджували особливості емоційно-поведінкових реакцій у тварин, яким моделювали синдром обструктивного апное-гіпопное сну. Для цього сконструювали пристрій, який за допомогою електромагнітного затвору викликає дозоване за часом змикання двох планок, між якими фіксується латексна тонкостінна муфта, одягнута на мордочки тварин, проксимальна частина яких щільно прилягає до шкіри голови. Тварини при цьому знаходились у медикаментозному сні. Дослідження проведено на 4; 12 і 18 доби. Результати. Під час моделювання інспіраторного апное внутрішньоплевральний тиск у них зростав у 5–6 разів. Досліджували емоційно-поведінкові реакції у 42 щурів за тестом «відкрите поле» з  інтервалом у 3 дні, загальною тривалістю 18 днів. Виявили погіршення значень горизонтальної та вертикальної активності й показників вегетативного балансу на тлі проведеного наркозу та, особливо, при моделюванні у них синдрому обструктивного апное сну, що засвідчувало їхню здатність до погіршення  адаптації, на відміну від інтактних тварин. Висновки. Для поглибленого вивчення феномену обструктивного апное-гіпопное сну доцільно застосовувати запропоновану експериментальну модель інспіраторного перекриття ротового та носових просвітів тварин на (2,2±0,2) с протягом кожної хвилини сну під час наркозу. При моделюванні обструктивного апное-гіпопное сну в щурів відбуваються функціональні зміни – пониження емоційно-поведінкових реакцій та вегетативного балансу, що вказує на виражені порушення адаптаційних механізмів

Disfunção dos músculos respiratórios de pacientes críticos sob ventilação mecânica por insuficiência respiratória aguda: revisão de literatura

Impairment of breathing muscles is one of many consequences of mechanical ventilation in critical patients. In some cases, muscle weakness is due to patients’ disease itself. According to experimental studies conducted with animals, diaphragm force decreases after 12 hours of controlled mechanical ventilation. However, many factors might be responsible for such breathing muscles dysfunction and consequent difficulty in weaning from mechanical ventilation. The aim of the present review was to search for the causes of breathing muscle alterations in patients who present acute respiratory failure. The search in main electronic databases led to selecting experimental and review studies published in the last 10 years, most of which were conducted with animal models. According to the reviewed studies, impairment of breathing muscles is multi-factorial and might be related to sepsis, medicine consumption, nutrition deprivation, and to the controlled mechanical ventilation itself. It is mandatory to identify each of these factors since, either isolated or associated, they increase respiratory muscle dysfunction.A disfunção dos músculos respiratórios é uma das conseqüências daventilação mecânica em paciente crítico. Em alguns casos a fraqueza muscular é decorrente de sua doença de base. Nota-se a redução da força diafragmática após 12 h de ventilação mecânica controlada de acordo com estudos experimentais em modelos animais. Entretanto, há vários fatores que podem ser responsáveis pela disfunção muscular respiratória e conseqüente dificuldade no desmame da VM. O objetivo desta revisão foi verificar as causas das alterações dos músculos respiratórios em pacientes que apresentam insuficiência respiratória aguda. A busca nas principais bases de dados eletrônicas resultou na seleção de estudos experimentais e de revisão dos últimos 10 anos, sendo a maioria realizada em modelos animais. Observou-se que a disfunção muscular respiratória é multifatorial, podendo estar relacionada à sepse, ao uso de medicamentos, à desnutrição e à própria ventilação mecânica controlada. É necessário identificar cada um desses fatores, visto que, isolados ou associados, potencializam a disfunção muscular respiratória

Epilepsy in adult patients with Down syndrome : a clinical-video EEG study

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28-64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6-60 years). Nine out of 22 patients had focal epilepsy, while nine had late-onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp-and-slow waves with frontal predominance. In the patients diagnosed with late-onset myoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode of myoclonic status epilepticus at the beginning or in the course of the disorder. After the first descriptions of late-onset myoclonic epilepsy by Genton and Paglia (1994), this is one of the largest patient cohorts reported. Our data confirm that epilepsy in adult patients with Down syndrome presents peculiar electroclinical characteristics which should be recognized early as prompt, effective treatment may be beneficial. [Published with video sequences]

Stroke-unit care for acute stroke patients: an observational follow-up study

Background Large numbers of stroke patients arrive at hospital at a very early stage, and eff ective treatments for the acute phase of the disease are available. However, evidence that patients with acute stroke benefi t from stroke-unit care is scarce. Our aim was to determine whether admission to a stroke unit, rather than a conventional ward, aff ected the outcome of patients with acute stroke. Methods We did an observational follow-up study of 11 572 acute stroke patients hospitalised within 48 h of the onset of symptoms either in a stroke unit (n=4936) or in a conventional ward (6636). Patients were identifi ed retrospectively from discharge records from 260 Italian hospitals. The primary outcome was mortality or disability (Rankin score greater than two), assessed prospectively by independent, masked assessors 2 years after admission. Analyses were adjusted for patient characteristics and clustered at the hospital level. Findings Overall, 1576 patients died in hospital; 2169 died during the follow-up period. 347 patients were lost to follow-up. Compared with conventional-ward care, stroke-unit care was associated with a reduced probability of death or being disabled at the end of follow-up (odds ratio 0\ub781, 95% CI 0\ub772\u20130\ub791; p=0\ub70001). The potential benefi t was signifi cant across all age ranges and clinical characteristics, except for unconsciousness. No specifi c elements of setting, organisation, or process of care were associated with outcome. Interpretation Admission to a stroke-unit ward with dedicated beds and staff within 48 h of onset should be recommended for all patients with acute stroke

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Sleep hygiene Protocol to Improve Sleep and Delirium In a Surgical Intensive Care Unit

Background: In a special report published in 2015 by the American Geriatrics Society (AGS), a postoperative delirium expert panel was chosen and gave recommendations for best practice for the reduction of delirium. The Institute of Medicine supported the following ten behavioral and nonpharmacological strategies for prevention of delirium: 1. Sensory enhancement (ensuring glasses, hearing aids, or listening amplifiers) 2. Mobility enhancement (ambulating at least twice per day if possible) 3. Cognitive orientation and therapeutic activities (tailored to the individual) 4. Pain control with scheduled acetaminophen if appropriate 5. Cognitive stimulation (if possible, tailored to the individual’s interests and mental status) 6. Simple communication standards and approaches to prevent the escalation of behavior 7. Nutritional and fluid repletion enhancement 8. Sleep enhancement (daytime sleep hygiene, relaxation, non –pharmacologic sleep protocol, and nighttime routine) 9. Medication review and appropriate medication management 10. Daily rounding by an interdisciplinary team to reinforce the interventions The best practice statement was review by both surgical and nonsurgical experts in the field of geriatric medicine and surgery and was accepted. The best practice statement is a call for change in the care of post-operative patients 65 years and older. The AGS Geriatric for Specialist Initiative (AGS-GSI) recognized delirium as the most common surgical complication in older adults, occurring in 5% to 50% of older patients after an operation. In the United States more than one-third of inpatient surgeries are performed on patients 65 years or older (Hall & DeFrances, 2010) making it imperative that clinicians caring for surgical patients understand optimal delirium care. Delirium is a serious complication for older adults because an episode of delirium can begin a cascade of deleterious clinical events, including other postoperative complications, prolonged hospitalization, loss of functional independence, and reduced cognitive function and death (Robinson & Raebirm, 2009). Cost to patients includes impact on long-term cognitive ability and loss of preoperative quality of life. Furthermore, cost to the health care system is estimated at $150 billion annually (Leslie & Marcantonio, 2008). This proposal will examine the implementation of the eighth recommendation which is the behavioral and nonpharmacological strategies for prevention of delirium; sleep enhancement with the introduction of a best practice sleep hygiene protocol (appendix I).No embarg

Chronobiology, sleep-related risk factors and light therapy in perinatal depression : the "Life-ON" project

Perinatal depression (PND) has an overall estimated prevalence of roughly 12\ua0%. Untreated PND has significant negative consequences not only on the health of the mothers, but also on the physical, emotional and cognitive development of their children. No certain risk factors are known to predict PND and no completely safe drug treatments are available during pregnancy and breastfeeding. Sleep and depression are strongly related to each other because of a solid reciprocal causal relationship. Bright light therapy (BLT) is a well-tested and safe treatment, effective in both depression and circadian/sleep disorders