742 research outputs found
Mito-nuclear coevolution and phylogenetic artifacts: the case of bivalve mollusks
Mito‐nuclear phylogenetic discordance in Bivalvia is well known. In particular, the monophyly of Amarsipobranchia (Heterodonta + Pteriomorphia), retrieved from mitochondrial markers, contrasts with the monophyly of Heteroconchia (Heterodonta + Palaeoheterodonta), retrieved from nuclear markers. However, since oxidative phosphorylation nuclear markers support the Amarsipobranchia hypothesis instead of the Heteroconchia one, interacting subunits of the mitochondrial complexes ought to share the same phylogenetic signal notwithstanding the genomic source, which is different from the signal obtained from other nuclear markers. This may be a clue of coevolution between nuclear and mitochondrial genes. In this work we inferred the phylogenetic signal from mitochondrial and nuclear oxidative phosphorylation markers exploiting different phylogenetic approaches and added two more datasets for comparison: genes of the glycolytic pathway and genes related to the biogenesis of regulative small noncoding RNAs. All trees inferred from mitochondrial and nuclear subunits of the mitochondrial complexes support the monophyly of Amarsipobranchia, regardless of the phylogenetic pipeline. However, not every single marker agrees with this topology: this is clearly visible in nuclear subunits that do not directly interact with the mitochondrial counterparts. Overall, our data support the hypothesis of a coevolution between nuclear and mitochondrial genes for the oxidative phosphorylation. Moreover, we suggest a relationship between mitochondrial topology and different nucleotide composition between clades, which could be associated to the highly variable gene arrangement in Bivalvia
Clinical Characteristics and Burden of Illness in Pediatric Patients with Narcolepsy
Abstract Background: Narcolepsy is a chronic and lifelong neurologic disorder with onset commonly occurring in childhood or adolescence, and affecting approximately 0.025% to 0.05% of the general population. The primary symptom is excessive daytime sleepiness, which is accompanied by cataplexy in 70% of patients. Other common symptoms include sleep paralysis, hallucinations upon falling asleep or waking, and disrupted nocturnal sleep. Narcolepsy is associated with a considerable burden of illness (BOI), which has been well characterized in adults, and is exacerbated by delays in symptom recognition, diagnosis, and intervention. METHODS: This review describes the specific characteristics and BOI of pediatric narcolepsy, using a wide range of published research data. RESULTS: Pediatric narcolepsy presents distinct challenges in diagnosis and management. Narcolepsy symptoms often initially manifest differently in children and adolescents versus adults, which may pose diagnostic dilemmas. Children often respond to sleepiness with irritability, hyperactivity, and poor attention, which may be misinterpreted as misbehavior or neurocognitive sequelae of other conditions. Pediatric cataplexy symptoms may include subtle and unusual facial expressions or choreic-like movements, which are not observed in adults. Insufficient sleep and circadian rhythm disorders presenting with excessive daytime sleepiness are common in adolescents, potentially confounding narcolepsy diagnosis. Pediatric narcolepsy is also associated with comorbidities including rapid weight gain, precocious puberty, and attention deficit hyperactivity disorder, and increased risk for deficits in social functioning, depression, and anxiety. School performance is also typically impaired, requiring special education services. CONCLUSIONS: Thus, the discrete BOI of pediatric narcolepsy underscores the need for prompt and accurate diagnosis, and appropriate treatment of this disorder
New approaches to the study of periodic leg movements during sleep in restless legs syndrome
Study Objectives: To describe a new approach for the analysis of quantity, type, and periodicity of the leg motor activity during sleep in patients with restless legs syndrome (RLS) and periodic leg movements (PLM). Methods: The following parameters were taken into account for LM: duration, amplitude, area under the curve, sleep stage, side, interval, and bilaterality. The analysis of inter-LM intervals was carried out by drawing their distribution graphs. A new index evaluated their periodicity and was validated by means of a Markovian analysis. The differences in inter-LM intervals, LM duration, and area under the curve between normal controls and patients and between the 3 patient subgroups identified on the basis of their periodicity were statistically analyzed. Setting: N/A Participants: Sixty-five patients with RLS and periodic LM and 22 young healthy controls. Measurements and Results: The RLS patients' inter-LM interval distribution graph showed a wide peak with a maximum located at around 15 to 30 seconds and extending from 10 to 90 seconds, not present in controls, and another peak for intervals less than 8 seconds, higher than that of controls. Three patient subgroups were identified with different proportions of these 2 peaks, periodicity, and Markovian parameters. Periodicity was not dependent on the periodic leg movement index. Patients showing the peak mainly at around 15 to 30 seconds tended to show slightly longer and higher area under the curve LM than did the other 2 subgroups. Conclusions: Our new approach seems to be useful in a new qualitative differentiation among patients with PLM, which is not possible by using the simple PLM index
Sleep disturbances and sleep disorders as risk factors for chronic postsurgical pain: A systematic review and meta-analysis
This systematic review and meta-analysis aimed at evaluating the role of sleep disturbances and sleep disorders in influencing presence and intensity of chronic postsurgical pain (CPSP). We included cohort studies which enrolled adults, assessed sleep disturbances or disorders before surgery, measured pain intensity, presence of pain, or opioid use at least three months after surgery. Eighteen studies were included in a narrative synthesis and 12 in a meta-analysis. Sleep disturbances and disorders were significantly related to CPSP, with a small effect size, r = 0.13 (95% CI 0.06–0.20). The certainty of evidence was rated low due to risk of bias and heterogeneity. In subgroup analyses the above association was significant in studies that used pain intensity as the outcome, but not in those that used presence of pain; in studies on patients who underwent total knee arthroplasty or other surgeries, but not in those on patients who had breast cancer surgery or total hip arthroplasty; in the single study that assessed insomnia and in studies that assessed sleep disturbances as predictors. A meta-regression showed that the follow-up length was positively associated with the overall estimate. Our findings suggest that presurgical sleep disturbances and disorders should be evaluated to detect patients at risk for CPSP. Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=27265
Electroencephalogram paroxysmal theta characterizes cataplexy in mice and children
Astute control of brain activity states is critical for adaptive behaviours and survival. In mammals and birds, electroencephalographic recordings reveal alternating states of wakefulness, slow wave sleep and paradoxical sleep (or rapid eye movement sleep). This control is profoundly impaired in narcolepsy with cataplexy, a disease resulting from the loss of orexin/hypocretin neurotransmitter signalling in the brain. Narcolepsy with cataplexy is characterized by irresistible bouts of sleep during the day, sleep fragmentation during the night and episodes of cataplexy, a sudden loss of muscle tone while awake and experiencing emotions. The neural mechanisms underlying cataplexy are unknown, but commonly thought to involve those of rapid eye movement-sleep atonia, and cataplexy typically is considered as a rapid eye movement sleep disorder. Here we reassess cataplexy in hypocretin (Hcrt, also known as orexin) gene knockout mice. Using a novel video/electroencephalogram double-blind scoring method, we show that cataplexy is not a state per se, as believed previously, but a dynamic, multi-phased process involving a reproducible progression of states. A knockout-specific state and a stereotypical paroxysmal event were introduced to account for signals and electroencephalogram spectral characteristics not seen in wild-type littermates. Cataplexy almost invariably started with a brief phase of wake-like electroencephalogram, followed by a phase featuring high-amplitude irregular theta oscillations, defining an activity profile distinct from paradoxical sleep, referred to as cataplexy-associated state and in the course of which 1.5-2 s high-amplitude, highly regular, hypersynchronous paroxysmal theta bursts (∼7 Hz) occurred. In contrast to cataplexy onset, exit from cataplexy did not show a predictable sequence of activities. Altogether, these data contradict the hypothesis that cataplexy is a state similar to paradoxical sleep, even if long cataplexies may evolve into paradoxical sleep. Although not exclusive to overt cataplexy, cataplexy-associated state and hypersynchronous paroxysmal theta activities are highly enriched during cataplexy in hypocretin/orexin knockout mice. Their occurrence in an independent narcolepsy mouse model, the orexin/ataxin 3 transgenic mouse, undergoing loss of orexin neurons, was confirmed. Importantly, we document for the first time similar paroxysmal theta hypersynchronies (∼4 Hz) during cataplexy in narcoleptic children. Lastly, we show by deep recordings in mice that the cataplexy-associated state and hypersynchronous paroxysmal theta activities are independent of hippocampal theta and involve the frontal cortex. Cataplexy hypersynchronous paroxysmal theta bursts may represent medial prefrontal activity, associated in humans and rodents with reward-driven motor impulse, planning and conflict monitorin
Is Whole-Body Cryostimulation an Effective Add-On Treatment in Individuals with Fibromyalgia and Obesity? A Randomized Controlled Clinical Trial
Pain severity, depression, and sleep disturbances are key targets for FM rehabilitation. Recent evidence suggests that whole-body cryostimulation (WBC) might be an effective add-on treatment in the management of FM. The purpose of this study was to evaluate the effects of an add-on WBC intervention to a multidisciplinary rehabilitation program on pain intensity, depressive symptoms, disease impact, sleep quality, and performance-based physical functioning in a sample of FM patients with obesity. We performed a randomized controlled trial with 43 patients with FM and obesity undergoing a multidisciplinary rehabilitation program with and without the addition of ten 2-min WBC sessions at −110 °C over two weeks. According to our results, the implementation of ten sessions of WBC over two weeks produced additional benefits. Indeed, both groups reported positive changes after the rehabilitation; however, the group that underwent WBC intervention had greater improvements in the severity of pain, depressive symptoms, disease impact, and quality of sleep. On the contrary, with respect to performance-based physical functioning, we found no significant between-group differences. Our findings suggest that WBC could be a promising add-on treatment to improve key aspects of FM, such as pain, depressive symptoms, disease impact and poor sleep quality
Impact of COVID-19 pandemic lockdown on narcolepsy type 1 management
Study Objectives: Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID-19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule. Methods: In the period between 10 April and 15 May 2020, we performed routine follow-up visits by telephone (as recommended during the COVID-19 emergency) to 50 patients >18 years old (40% males) under stable long-term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job (“lost occupation”). Current sleep–wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups. Results: At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep-related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ. Conclusions: Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight
Child Neurology: A Case Series of Heterogeneous Neuropsychiatric Symptoms and Outcome in Very Early-Onset Narcolepsy Type 1
Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy (i.e., sudden loss of muscle tone during wakefulness triggered by emotions), and REM sleep-related manifestations that can present with a peculiar phenotype when arising at a pediatric age. Several features of childhood-onset narcolepsy type 1 are also common in neuropsychiatric conditions; discrete neuropsychiatric comorbidity has also been demonstrated. Here, we report on 3 children with very early narcolepsy type 1. All 3 patients had psychiatric features at the time of symptom onset coupled with peculiar motor disturbances. The course of narcolepsy symptoms also paralleled neuropsychiatric symptoms, suggesting a possible intrinsic link between sleep and psychological features. Multidisciplinary management is mandatory for pediatric narcolepsy type 1 since prompt disease management addressing neuropsychiatric symptoms could lead to better clinical outcomes and quality of life
Exploring Addictive Online Behaviors in Patients with Narcolepsy Type 1
Background: Narcolepsy type 1 (NT1) is a rare neurological sleep disorder caused by the loss of neurons that produce hypocretin—a peptide that plays a crucial role in addictive behaviors. We aimed to compare, for the first time, levels of problematic online gaming, problematic social media use, and compulsive Internet use between NT1 patients and healthy controls (HC), and to evaluate the association between anxiety, depression, and emotion dysregulation with addictive online behaviors in NT1 patients. Methods: A total of 43 patients with NT1 and 86 sex-and age-matched HC participated in an online cross-sectional survey. Results: NT1 patients did not differ from HC in terms of problematic social media use and compulsive Internet use but displayed higher levels of problematic online gaming compared to HC. Higher levels of emotion dysregulation were significantly associated with higher levels of problematic social media use and compulsive Internet use, while none of the tested factors were associated with problematic online gaming. Conclusion: NT1 patients and HC had similar levels of problematic social media use and compulsive Internet use, but NT1 patients showed higher levels of problematic online gaming. Emotion dysregulation might be an intervention target for reducing compulsive Internet use and problematic social media use
Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behavior Disorder
Background: Melanopsin retinal ganglion cell (mRGC)-mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α-synucleinopathies. Objectives: To quantitatively compare PLR and mRGC-mediated contribution to PLR in 16 iRBD patients and 16 healthy controls. Methods: iRBD and controls underwent extensive neuro-ophthalmological evaluation and chromatic pupillometry. In iRBD, PLR metrics were correlated with clinical variables and with additional biomarkers including REM atonia index (RAI), DaTscan, and presence of phosphorylated-α-synuclein (p-α-syn) deposition in skin biopsy. Results: We documented higher baseline pupil diameter and decreased rod-transient PLR amplitude in iRBD patients compared to controls. PLR rod-contribution correlated with RAI. Moreover, only iRBD patients with evidence of p-α-syn deposition at skin biopsy showed reduced PLR amplitude compared to controls. Conclusion: The observed PLR abnormalities in iRBD might be considered as potential biomarkers for the risk stratification of phenoconversion of the disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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