International consensus on sleep problems in pediatric palliative care: Paving the way.

OBJECTIVE: Sleep problems constitute a common and heterogeneous complaint in pediatric palliative care (PPC), where they often contribute to disease morbidity and cause additional distress to children and adolescents and their families already facing the burden of life-threatening and life-limiting conditions. Despite the significant impact of sleep problems, clinical evidence is lacking. The application of general pediatric sleep recommendations appears insufficient to address the unique challenges of the PPC dimension in terms of disease variability, duration, comorbidities, complexity of needs, and particular features of sleep problems related to hospice care. Therefore, we initiated an international project aimed at establishing a multidisciplinary consensus. METHODS: A two-round Delphi approach was adopted to develop recommendations in the areas of Definition, Assessment/Monitoring, and Treatment. After selecting a panel of 72 worldwide experts, consensus (defined as ≥75% agreement) was reached through an online survey. RESULTS: At the end of the two voting sessions, we obtained 53 consensus recommendations based on expert opinion on sleep problems in PPC. CONCLUSIONS: This study addresses the need to personalize sleep medicine's approach to the palliative care setting and its peculiarities. It provides the first international consensus on sleep problems in PPC and highlight the urgent need for global guidance to improve sleep-related distress in this vulnerable population and their caregivers. Our findings represent a crucial milestone that will hopefully enable the development of guidelines in the near future.

Melatonin use in managing insomnia in children with autism and other neurogenetic disorders - An assessment by the international pediatric sleep association (IPSA).

Though it is widely prescribed for improving sleep of children with autism and other neurogenetic disorders, there is a need for practical guidance to clinicians on the use of melatonin for managing insomnia in this population. Because data were either lacking or inconclusive, a task force was established by the International Pediatric Sleep Association (IPSA) to examine the literature based on clinical trials from 2012 onwards. A summary of evidence pertaining to melatonin's utility and potential side effects, practice-related caveats, and insights for use are published herewith.

Sleep deprivation in early life: Cellular and behavioral impacts.

Sleep deprivation has become increasingly prevalent in contemporary society, and the consequences of this reality such as cognitive impairment and metabolic disorders, are widely investigated in the scientific scenario. However, the impact of sleep deprivation on the health of future generations is a challenge, and researchers are focusing their attention on this issue. Thus, this review aims to describe the impact of sleep deprivation in early life in animal models, particularly rodents, discussing the molecular physiology impacted by prolonged wakefulness in early life, as well as the changes that interfere with neurodevelopmental processes. Additionally, it explores the changes impacting metabolic mechanisms and discusses both the short- and long-term consequences of these processes on endocrine, behavioral, and cognitive functions. Finally, we briefly address some strategies to mitigate the adverse effects of sleep deprivation.

Consequences of the Covid-19 pandemic in children and adolescents with attention deficit hyperactivity disorder - a systematic review.

OBJECTIVE: In this systematic review (SR), the authors aimed to identify the possible impact of the social restriction imposed by the Coronavirus Disease-19 (COVID-19) pandemic on children/adolescents with Attention Deficit Hyperactivity Disorder (ADHD). DATA SOURCES: This SR was registered on PROSPERO CRD42021255569. Eligible articles were selected from PubMed, Embase, and LILACS, according to the following characteristics: ADHD patients < 18 years old, exposed to the COVID-19 pandemic, and the outcomes, medications, relationships, sleep, media use, remote learning, and comorbidities such as depression/sadness, inattention, anxiety, and irritability/aggressiveness. Newcastle-Ottawa Scale (NOS) for cohort, cross-sectional and case-control studies was used to assess methodological quality and the risk of bias. SUMMARY OF FINDINGS: Of the 222 articles identified, 27 were included, with information on 7,235 patients. Most studies (n = 22) were cross-sectional and received a mean NOS 4.63/10 followed by longitudinal (n = 4) with 3.75/8 points and case-control (n = 1), with 3/9 points. The pandemic affected patients' access to treatment, behavior, and sleep. Difficulties in remote learning and increased use of social media were described, as well as significant and positive changes in relationships with family and peers. CONCLUSION: Although the studies were heterogeneous, they indicated that the pandemic-related issues experienced by patients with ADHD were mostly manifested affecting their behavior and sleep patterns.

Consequences of the Covid-19 pandemic in children and adolescents with attention deficit hyperactivity disorder - a systematic review

Abstract Objective In this systematic review (SR), the authors aimed to identify the possible impact of the social restriction imposed by the Coronavirus Disease-19 (COVID-19) pandemic on children/adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Data sources This SR was registered on PROSPERO CRD42021255569. Eligible articles were selected from PubMed, Embase, and LILACS, according to the following characteristics: ADHD patients < 18 years old, exposed to the COVID-19 pandemic, and the outcomes, medications, relationships, sleep, media use, remote learning, and comorbidities such as depression/sadness, inattention, anxiety, and irritability/aggressiveness. Newcastle-Ottawa Scale (NOS) for cohort, cross-sectional and case-control studies was used to assess methodological quality and the risk of bias. Summary of findings Of the 222 articles identified, 27 were included, with information on 7,235 patients. Most studies (n = 22) were cross-sectional and received a mean NOS 4.63/10 followed by longitudinal (n = 4) with 3.75/8 points and case-control (n = 1), with 3/9 points. The pandemic affected patients' access to treatment, behavior, and sleep. Difficulties in remote learning and increased use of social media were described, as well as significant and positive changes in relationships with family and peers. Conclusion Although the studies were heterogeneous, they indicated that the pandemic-related issues experienced by patients with ADHD were mostly manifested affecting their behavior and sleep patterns.

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

Functional and structural insights into the multi-step activation and catalytic mechanism of bacterial ExoY nucleotidyl cyclase toxins bound to actin-profilin.

ExoY virulence factors are members of a family of bacterial nucleotidyl cyclases (NCs) that are activated by specific eukaryotic cofactors and overproduce cyclic purine and pyrimidine nucleotides in host cells. ExoYs act as actin-activated NC toxins. Here, we explore the Vibrio nigripulchritudo Multifunctional-Autoprocessing Repeats-in-ToXin (MARTX) ExoY effector domain (Vn-ExoY) as a model for ExoY-type members that interact with monomeric (G-actin) instead of filamentous (F-actin) actin. Vn-ExoY exhibits moderate binding affinity to free or profilin-bound G-actin but can capture the G-actin:profilin complex, preventing its spontaneous or VASP- or formin-mediated assembly at F-actin barbed ends in vitro. This mechanism may prolong the activated cofactor-bound state of Vn-ExoY at sites of active actin cytoskeleton remodelling. We present a series of high-resolution crystal structures of nucleotide-free, 3'-deoxy-ATP- or 3'-deoxy-CTP-bound Vn-ExoY, activated by free or profilin-bound G-actin-ATP/-ADP, revealing that the cofactor only partially stabilises the nucleotide-binding pocket (NBP) of NC toxins. Substrate binding induces a large, previously-unidentified, closure of their NBP, confining catalytically important residues and metal cofactors around the substrate, and facilitating the recruitment of two metal ions to tightly coordinate the triphosphate moiety of purine or pyrimidine nucleotide substrates. We validate critical residues for both the purinyl and pyrimidinyl cyclase activity of NC toxins in Vn-ExoY and its distantly-related ExoY from Pseudomonas aeruginosa, which specifically interacts with F-actin. The data conclusively demonstrate that NC toxins employ a similar two-metal-ion mechanism for catalysing the cyclisation of nucleotides of different sizes. These structural insights into the dynamics of the actin-binding interface of actin-activated ExoYs and the multi-step activation of all NC toxins offer new perspectives for the specific inhibition of class II bacterial NC enzymes.

Health consequences and daily life modifications in children and adolescents with epilepsy during the COVID-19 pandemic - a systematic review: Running Title: Covid-19 Pandemic in Children/Adolescents with Epilepsy.

PURPOSE: To describe the impact of the COVID-19 pandemic on the health care and daily life of children and adolescents with epilepsy. METHODS: This systematic review followed the preferred reporting items guidelines and was registered on the PROSPERO platform (CRD42021255931). The PECO (Patient, Exposure, Comparison, Outcome) framework criteria were as follows: people with epilepsy (0-18 years old); exposed to the COVID-19 pandemic; and outcomes, including epilepsy type, time of clinical diagnosis, seizure exacerbation, treatment and medications, need for emergency because of seizures, sleep, behavior, comorbidities and/or concerns, social and/or economic impact, insurance status, electronic device use, telemedicine, and distance learning. Literature searches for cross-sectional and longitudinal studies were conducted on Embase and PubMed. The methodological quality of identified studies was assessed using the Newcastle‒Ottawa Scale (NOS). RESULTS: Data were extracted from 23 eligible out of 597 identified articles and included 31,673 patients. The mean NOS scores for cross-sectional study design was 3.84/10, and for longitudinal, it was 3.5/8 stars. Seizure exacerbations were reported in three studies, difficulties with access to anti-seizure medications in two, changes in dosage in five, and visit postponed or cancelation in five studies. Problems with sleep were highlighted in three, issues related to distance learning in two, an increased time spent on electronic devices in three, and increased behavioral problems in eight studies. Telemedicine, when available, was described as useful and supporting patient's needs. CONCLUSION: The pandemic affected the health care and lifestyle of young individuals with epilepsy. The main problems described revolved around seizure control, accessing anti-seizure medication, sleep and behavioral complains.

Application of the International League Against Epilepsy Neonatal Seizure Framework to an international panel of medical personnel.

OBJECTIVE: The International League Against Epilepsy (ILAE) Neonatal Seizure Framework was tested by medical personnel. METHODS: Attendees at the 2016 ILAE European Congress on Epileptology in Prague, the International Video-EEG Course in Pediatric Epilepsies in Madrid 2017, and a local meeting in Utrecht 2018, were introduced to the proposed ILAE neonatal classification system with teaching videos covering the seven types of clinical seizures in the proposed neonatal classification system. Five test digital video recordings of electroencephalography (EEG)-confirmed motor neonatal seizures were then shown and classified by the rater based on their knowledge of the proposed ILAE Neonatal Seizure Framework. A multi-rater Kappa statistic was used to assess the agreement between observers and the true diagnosis. RESULTS: The responses of 194 raters were obtained. There was no single predominant classification system that was currently used by the raters. Using the ILAE framework, 78%-93% of raters correctly identified the clinical seizure type for each neonate; the overall inter-rater agreement (Kappa statistic) was 0.67. The clonic motor seizure type was most frequently accurately identified (93% of the time; κ = 0.870). EEG technicians correctly identified all presented motor seizure types more frequently than any other group (accuracy = 0.9). SIGNIFICANCE: The ILAE Neonatal Seizure Framework was judged by most raters to be better than other systems for the classification of clinical seizures. Among all seizure types presented, clonic seizures appeared to be the easiest to accurately identify. Average accuracy across the five seizure types was 84.5%. These data suggest that the ILAE neonatal seizure classification may be used by all healthcare professionals to correctly identify the predominant clinical seizure type.

Motor and cognitive outcomes of neonates with low birth weight in Brazil: a systematic review and meta-analysis.

BACKGROUND: Data on the outcomes of preterm newborns in South American countries are scarce. Given the great effect of low birth weight (LBW) and/or prematurity on children's neurodevelopment, it is extremely necessary to conduct studies on these phenomena in greater depth in more heterogeneous populations such as those ones from countries with limited resources. METHODS: We conducted a comprehensive literature search on databases including PubMed, the Cochrane Library, and Web of Science for articles published in Portuguese and English up to March 2021 involving children born and evaluated in Brazil. The analysis of the risk of bias was adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and used to evaluate the methodology of the included studies. RESULTS: From the eligible trials, 25 articles were selected for qualitative synthesis, and 5 of those, for quantitative synthesis (meta-analysis). The meta-analyses showed that children born with LBW presented lower scores on motor development when compared with controls (standardized mean difference: -1.15; 95% confidence interval [95%CI]: -1.56--0.73]; I2: 80%) and also scored lower in terms of cognitive development (standardized mean difference: -0.71; 95% CI: -0.99--0.44; I2: 67%). CONCLUSION: The results of the present study reinforce that impaired motor and cognitive functions can be a significant long-term outcome of LBW. The lower the gestational age at delivery, the higher the risk of impairment in those domains. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42019112403.

ANTECEDENTES: Dados sobre desfechos de recém-nascidos prematuros em países da América do Sul são escassos. Dado o grande efeito do baixo peso ao nascer (BPN) e/ou da prematuridade no neurodesenvolvimento das crianças, é extremamente necessária a realização de estudos que investiguem esses fenômenos com maior profundidade em populações mais heterogêneas. MéTODOS: Realizou-se uma busca da literatura em bases de dados, incluindo PubMed, Cochrane Library e Web of Science, por artigos publicados em português e inglês até março de 2021 envolvendo crianças nascidas e avaliadas no Brasil. A análise de risco de viés foi adaptada da declaração de Fortalecimento do Relato de Estudos Observacionais em Epidemiologia (Strengthening the Reporting of Observational Studies in Epidemiology, STROBE), que foi utilizada para avaliar a metodologia dos estudos. RESULTADOS: Dos estudos elegíveis, 25 artigos foram selecionados para síntese qualitativa, e 5 desses 25, para síntese quantitativa (metanálise). As metanálises mostraram que crianças nascidas com BPN apresentaram pontuação menor em desenvolvimento motor quando comparadas aos controles (diferença média padronizada, −1,15; intervalo de confiança de 95% [IC95%]: −1,56­−0,73]; I2: 80%) e pontuação também menor em termos de desenvolvimento cognitivo (diferença média padronizada, −0,71; IC95%: −0,992−0,44; I2: 67%). CONCLUSãO: Os resultados deste estudo reforçam que o comprometimento das funções motoras e cognitivas pode ser um desfecho significativo de longo prazo do BPN. Quanto menor a idade gestacional no momento do parto, maior o risco de prejuízo nesses domínios. O protocolo do estudo foi registrado no banco de dados International Prospective Register of Systematic Reviews (PROSPERO) sob o número CRD42019112403.

The Influence of Parental Sleep and Experiences Related to COVID-19 on Sleep in Children and Adolescents between 2020 and 2021 in Brazil.

The study aimed to evaluate the influence of parental sleep and experiences related to COVID-19 on sleep changes in children and adolescents in the period between 2020 and 2021 in Brazil and further compare the sleep of adults with and without children. This is a longitudinal web-survey study. Participants were invited to respond to a questionnaire regarding sleep characteristics, mental health issues, and work/lifestyle modifications in two waves of the pandemic (April-July 2020 and 2021). A total of 1172 adults answered both questionnaires, and 281 were dyads (parent-child/adolescent). Parent and non-parent adult responders had similar sociodemographic data, with a predominance of the female sex and self-declared white skin color prevailing along with higher levels of education in both groups. The prevalence of sleep problems in adults varied from 20.6% to 30.2% in the parent group and from 16.9% to 30.1% in non-parents. The prevalence of sleep problems in children and adolescents raised from 2020 to 2021 (respectively, 48% and 49.5%) but differences were not statistically significant. The multivariate logistic model showed in both years that changes in children's/adolescents' sleep was related to parents working at home, infected family/friends, time of exposure to COVID-19, and daytime sleep dysfunction. Our data showed that parental sleep and experiences related to COVID-19 influenced sleep changes in children and adolescents. Parents had a significant difference in daytime sleepiness compared to the group without children.

Consequences of post-weaning sleep deprivation on behaviour and oxidative stress parameters in rat plasma and brain.

Sleep is essential for health: Adequate sleep is essential for healthy development and sleep deprivation results in several consequences. Indeed, sleep deprivation early in life is associated with poor behaviour and cognition, as well as impaired mental and physical health. Preclinical studies have shown that sleep deprivation alters several physiological functions later in life such as the cardiovascular, immune and endocrine systems, resulting in altered oxidative states. Most of the preclinical literature is focused on adult animals, and little is known about oxidative alterations during development, especially in the context of sleep deprivation. Hence, we adapted a classic and well-documented model of sleep deprivation, paradoxical sleep deprivation using multiple platforms, for juvenile rats and explored central and peripheral oxidative parameters, as well as the behavioural consequences of sleep deprivation post-weaning. We showed that 96 h of paradoxical sleep deprivation induced a significant reduction in body weight, decreased sucrose preference-a behaviour suggestive of anhedonia-and increased glucose and decreased cholesterol in the plasma. In the brain, we observed a decrease in reduced glutathione levels in the medial prefrontal cortex and an increase in thiobarbituric acid reactive substance levels in the hypothalamus, indicating oxidative damage in these regions. Taken together, our findings suggest that paradoxical sleep deprivation during development induces anhedonic behaviour and promotes central and peripheral alterations in oxidative parameters.

Effects of the COVID-19 pandemic on sleep quality in children and adolescents: A systematic review and meta-analysis.

We synthesise the literature on the potential influence of the COVID-19 pandemic on sleep quality in children and adolescents. The search identified studies that examined the relationship between sleep quality and disorders during the COVID-19 pandemic. It began in May 2021 and has had two updates with the last in January 2022. The databases used were LILACS, PubMed, and EMBASE. Random effects models were performed to explore heterogeneity between studies. Data were presented as continuous variables (mean value and standard deviation) to perform a meta-analysis. Twenty-nine studies from 16 countries were identified: Nine had children and eight had adolescents. The overall quality of the studies ranged from high (27.6%) to medium (65.5%) and low (6.9%). Eight studies were eligible for meta-analysis. There was an increase in sleep duration during the pandemic when compared with the previous period 0.33 (95%CI -0.07; 0.60) (p < 0.001) and late bedtime 0.78 (95%CI -0.33; 1.22) (p < 0.001). A trend toward reduced sleep efficiency was also detected 0.54 (95%CI -0.75; -0.33) p = 0.20. Parents' reports of increased use of screen media/electronic devices were associated with worse sleep quality. The results suggest an influence of the pandemic on sleep characteristics such as increased sleep duration, late bedtimes, and poor sleep quality. These alterations were related to changes in family routines during this period.

Motor and cognitive outcomes of neonates with low birth weight in Brazil: a systematic review and meta-analysis / Desfechos motores e cognitivos de recém-nascidos com baixo peso ao nascer no Brasil: uma revisão sistemática e metanálise

Abstract Background Data on the outcomes of preterm newborns in South American countries are scarce. Given the great effect of low birth weight (LBW) and/or prematurity on children's neurodevelopment, it is extremely necessary to conduct studies on these phenomena in greater depth in more heterogeneous populations such as those ones from countries with limited resources. Methods We conducted a comprehensive literature search on databases including PubMed, the Cochrane Library, and Web of Science for articles published in Portuguese and English up to March 2021 involving children born and evaluated in Brazil. The analysis of the risk of bias was adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and used to evaluate the methodology of the included studies. Results From the eligible trials, 25 articles were selected for qualitative synthesis, and 5 of those, for quantitative synthesis (meta-analysis). The meta-analyses showed that children born with LBW presented lower scores on motor development when compared with controls (standardized mean difference: -1.15; 95% confidence interval [95%CI]: -1.56--0.73]; I2: 80%) and also scored lower in terms of cognitive development (standardized mean difference: -0.71; 95% CI: -0.99--0.44; I2: 67%). Conclusion The results of the present study reinforce that impaired motor and cognitive functions can be a significant long-term outcome of LBW. The lower the gestational age at delivery, the higher the risk of impairment in those domains. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42019112403.

Resumo Antecedentes Dados sobre desfechos de recém-nascidos prematuros em países da América do Sul são escassos. Dado o grande efeito do baixo peso ao nascer (BPN) e/ou da prematuridade no neurodesenvolvimento das crianças, é extremamente necessária a realização de estudos que investiguem esses fenômenos com maior profundidade em populações mais heterogêneas. Métodos Realizou-se uma busca da literatura em bases de dados, incluindo PubMed, Cochrane Library e Web of Science, por artigos publicados em português e inglês até março de 2021 envolvendo crianças nascidas e avaliadas no Brasil. A análise de risco de viés foi adaptada da declaração de Fortalecimento do Relato de Estudos Observacionais em Epidemiologia (Strengthening the Reporting of Observational Studies in Epidemiology, STROBE), que foi utilizada para avaliar a metodologia dos estudos. Resultados Dos estudos elegíveis, 25 artigos foram selecionados para síntese qualitativa, e 5 desses 25, para síntese quantitativa (metanálise). As metanálises mostraram que crianças nascidas com BPN apresentaram pontuação menor em desenvolvimento motor quando comparadas aos controles (diferença média padronizada, -1,15; intervalo de confiança de 95% [IC95%]: -1,56--0,73]; I2: 80%) e pontuação também menor em termos de desenvolvimento cognitivo (diferença média padronizada, -0,71; IC95%: -0,992-0,44; I2: 67%). Conclusão Os resultados deste estudo reforçam que o comprometimento das funções motoras e cognitivas pode ser um desfecho significativo de longo prazo do BPN. Quanto menor a idade gestacional no momento do parto, maior o risco de prejuízo nesses domínios. O protocolo do estudo foi registrado no banco de dados International Prospective Register of Systematic Reviews (PROSPERO) sob o número CRD42019112403.

Translation and language validation of the Epworth sleepiness scale for children and adolescents (ESS-CHAD) into Brazilian Portuguese.

Objective: This study aimed to translate the Epworth sleepiness scale for children and adolescents (ESS-CHAD) into Brazilian Portuguese. Material and Methods: The translation and language validation processes were carried out through translation, back translation, technical review, assessment of verbal comprehension/clarity of the scale by experts (four pediatric neurologists). After they have reached a final version of the ESS-HAD a sample of asymptomatic children and adolescents that were participants in another sleep project were invited to read and complete the questionnaire to evaluate comprehension by the aimed population. Results: Two independent researchers made the forward translation and it has around 90% of concordance. Minor disagreements were related to the position of adjectives in the sentence. No major difficulties were reported by the 3rd researcher that performed the back translation. After a consensus meeting with the four participants, we have reached a final version of the questionnaire. In the cognitive interviews, the scale was reportedly easy to understand to the 23 respondents. One adolescent suggested clarifying whether question 2 (likelihood of falling asleep watching TV or a video), referred to daytime or nighttime. The total ESS-CHAD score in this asymptomatic sample varied from 0-17, a mean score of 7.08±5.65. Discussion: The final version of the ESS-CHAD in Brazilian Portuguese was approved by the copyright owners and was well understandable by caregivers and adolescents. More studies are now necessary to use this questionnaire in a larger target population to verify its validity and internal consistency.

COVID-19 Pandemic and Autism Spectrum Disorder, Consequences to Children and Adolescents - a Systematic Review.

In this systematic review, we aimed to identify the impact of the COVID-19 pandemic on children/adolescents with a diagnosis of autism spectrum disorder (ASD). The protocol was registered on PROSPERO CRD42021255848. Articles were selected from PubMed, Embase, and LILACS according to these characteristics: patients from zero to 18 years old, exposed to the COVID-19 pandemic, impact on social communication/interaction and restricted/repetitive behavior domains. The Newcastle-Ottawa Scale was used to assess methodological quality and the risk of bias. Of the 351 articles initially identified, 26 were finally included with information on 8,610 patients. Although the studies were heterogeneous, they indicated that the pandemic-related issues experienced by patients with ASD were mostly manifested in their behavior and sleep patterns. Supplementary Information: The online version contains supplementary material available at 10.1007/s40489-022-00344-4.

Clinical profile of a cohort of neonates with seizures: Association between semiology, etiology, and electroencephalographic findings.

BACKGROUND: Seizures are the most common sign of neurologic dysfunction, reflecting a wide variety of central nervous system disorders. METHODS: A retrospective cross-sectional study of neonates with a clinical diagnosis of seizures was conducted in order to verify relationships between clinical aspects and EEG findings. Patients were divided into 3 groups according to the EEG recording available as: 1) with confirmatory ictal EEG; 2) with altered but non-ictal EEG; and 3) without any EEG recording. Variables related to pregnancy and birth history, neonatal complications, and seizure semiology (by video or clinical description) were compared to EEG findings. RESULTS: 97 neonates were included (39.1% preterm, 54.6% male), 71 with available EEG data (56.3% with ictal EEG). The group without EEG presented clinical characteristics significantly different from the others such as extreme prematurity, low birth weight, and higher neonatal mortality (P = 0.002, 0.001, and 0.003, respectively). The most common etiology was hypoxic-ischemic encephalopathy (HIE) (46.4%) followed by vascular disorders, which predominated in extremely preterm neonates (P = 0.006). Sequential seizure was the most common type (44.6%) and was more frequently identified in term neonates (46%). In 51.2% of the ictal recordings the main finding was electrographic seizure without clinical manifestation. Discharge using antiseizure medication was higher among those with ictal or altered non-ictal EEG (P < 0.001). CONCLUSIONS: HIE is still a frequently etiology for neonatal seizures. Even if the patients in the sample were not under continuous EEG, the substantial proportion of electrographic seizures without clinical manifestations detected suggests the importance of continuous EEG monitoring in neonates at increased risk of seizures.

Bacterial Nucleotidyl Cyclases Activated by Calmodulin or Actin in Host Cells: Enzyme Specificities and Cytotoxicity Mechanisms Identified to Date.

Many pathogens manipulate host cell cAMP signaling pathways to promote their survival and proliferation. Bacterial Exoenzyme Y (ExoY) toxins belong to a family of invasive, structurally-related bacterial nucleotidyl cyclases (NC). Inactive in bacteria, they use proteins that are uniquely and abundantly present in eukaryotic cells to become potent, unregulated NC enzymes in host cells. Other well-known members of the family include Bacillus anthracis Edema Factor (EF) and Bordetella pertussis CyaA. Once bound to their eukaryotic protein cofactor, they can catalyze supra-physiological levels of various cyclic nucleotide monophosphates in infected cells. Originally identified in Pseudomonas aeruginosa, ExoY-related NC toxins appear now to be more widely distributed among various γ- and ß-proteobacteria. ExoY-like toxins represent atypical, poorly characterized members within the NC toxin family. While the NC catalytic domains of EF and CyaA toxins use both calmodulin as cofactor, their counterparts in ExoY-like members from pathogens of the genus Pseudomonas or Vibrio use actin as a potent cofactor, in either its monomeric or polymerized form. This is an original subversion of actin for cytoskeleton-targeting toxins. Here, we review recent advances on the different members of the NC toxin family to highlight their common and distinct functional characteristics at the molecular, cytotoxic and enzymatic levels, and important aspects that need further characterizations.

Sleep quality among parents and their children during COVID-19 pandemic

Abstract Objective: To evaluate sleep characteristics of parents and their children during the COVID-19 pandemic and predictors for sleep disturbances. Methods: Cross-sectional web-based study using an online survey made available for dyads of parents and their children during the 7th week of quarantine in southern Brazil. Parents' and adolescents' sleep were characterized using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. For children aged 0-3 years parents completed the Brief Infant Sleep Questionnaire, for those aged 4-12 years the Sleep Disturbance Scale for Children. Parents also informed, subjectively, their perception about sleep habits during social distancing. Multiple regression was run to predict sleep disturbances in adults using independent variables: sex, income, education, children age, and children with sleep disturbances. Results: Data from 577 dyads showed sleep alterations in 69,8% of adults, in 58,6% of children aged 0-3 years, 33,9% in the 4-12 years range (with a predominance of disorders of initiating or maintaining sleep), and 56,6% in adolescents. Sex (female) and children with sleep disturbances were significant predictors of a sleep problem in parents (p < 0.005). Subjective perception revealed complaints related to emotional concerns such as anxiety and fear in adults and due to alterations in routine in children and adolescents. Conclusion: The present study's data showed an increased rate of sleep problems among families during quarantine both measured by validated instruments and also based on personal perception.