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Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (ß = 0.50, p < 0.001) and time between treatment administration and the sleep episode (ß = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (ß = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.
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Melatonina , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono , Melatonina/administração & dosagem , Humanos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Relação Dose-Resposta a Droga , Sono/efeitos dos fármacosRESUMO
Background: Persons with specific phobias typically generalize the dangerousness of the phobic animal to all members of its species, possibly as a result of malfunctioning brain circuitry normally providing quick and dirty identification of evolutionary-relevant stimuli. An objective assessment of which perceptual features make an animal more or less scary to phobic and non-phobic people would help overcome the limitations of the few studies available so far, based on self-reports. Objective: To achieve this aim, we built an augmented reality setting where volunteers with different levels of fear of spiders were asked to make holographic spiders that look either dangerous or harmless. To reach this goal, a computerized interface allowed participants to modify the spider's perceptual features (hairiness, body/leg size, and locomotion) in real time. Results: On average, the dangerous spiders were made hairy, thick, and moving according to spider-like locomotion; coherently, the harmless spiders were made hairless, slim, and moving according to a butterfly-like locomotion. However, these averaged preferences could not fully describe the complex relationship between perceptual preferences with each other and with arachnophobia symptoms. An example of a key finding revealed by cluster analysis is the similarity in perceptual preferences among participants with little or no fear of spiders, whereas participants with more arachnophobia symptoms expressed more varying preferences. Conclusion: Perceptual preferences toward the spider's features were behaviorally assessed through an observational study, objectively confirming a generalization effect characterizing spider-fearful participants. These results advance our knowledge of phobic preferences and could be used to improve the acceptability of exposure therapies.
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OBJECTIVES: In a cross-sectional study, we explored possible differences in sleep parameters between SLE patients and age- and gender-matched healthy controls through actigraphic and self-reported measures. Furthermore, we aimed to identify possible predictors of such disturbances in the patient cohort. METHODS: Participants' sociodemographic data and sleep parameters were collected. Sleep parameters were evaluated through the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and 7-day actigraphic monitoring. The 10-item Perceived Stress Scale was used to investigate stress. Disease activity and daily glucocorticoid dose were assessed in SLE patients. Possible predictors of the SLE group were explored through two binomial logistic models. Within the SLE group, possible predictors of sleep parameters were tested estimating multiple linear regression models. RESULTS: A total of 40 SLE patients and 33 controls were included in the study. The SLE group showed worse sleep maintenance actigraphic parameters (i.e. sleep efficiency and wake after sleep onset), higher total sleep time and higher perceived stress. Within the SLE cohort, the daily glucocorticoids dose was associated with an impairment in sleep maintenance despite no reduction in sleep duration, typical of normal sleep duration insomnia, whereas perceived stress was associated with short sleep duration insomnia. CONCLUSION: Compared with healthy controls, SLE patients showed worse sleep quality and greater perceived stress severity. As glucocorticoids and perceived stress are associated with different types of insomnia in these patients, a multidimensional approach to both sleep characterization and therapy might be preferred.
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Lúpus Eritematoso Sistêmico , Testes Psicológicos , Distúrbios do Início e da Manutenção do Sono , Humanos , Autorrelato , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Estudos Transversais , Sono , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).
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Hipertensão Pulmonar , Disfunção Ventricular Direita , Humanos , Ecocardiografia sob Estresse/efeitos adversos , Circulação Pulmonar , Teste de Esforço/efeitos adversos , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular Direita/fisiologia , Disfunção Ventricular Direita/diagnóstico por imagemRESUMO
OBJECTIVES: The disruption of the blood-brain barrier (BBB) is a key and early feature in the pathogenesis of demyelinating multiple sclerosis (MS) lesions and has been neuropathologically demonstrated in both active and chronic plaques. The local overt BBB disruption in acute demyelinating lesions is captured as signal hyperintensity in post-contrast T1-weighted images because of the contrast-related shortening of the T1 relaxation time. On the contrary, the subtle BBB disruption in chronic lesions is not visible at conventional radiological evaluation but it might be of clinical relevance. Indeed, persistent, subtle BBB leakage might be linked to low-grade inflammation and plaque evolution. Here we hypothesised that 3D Quantitative Transient-state Imaging (QTI) was able to reveal and measure T1 shortening (ΔT1) reflecting small amounts of contrast media leakage in apparently non-enhancing lesions (ANELs). MATERIALS AND METHODS: Thirty-four patients with relapsing remitting MS were included in the study. All patients underwent a 3 T MRI exam of the brain including conventional sequences and QTI acquisitions (1.1 mm isotropic voxel) performed both before and after contrast media administration. For each patient, a ΔT1 map was obtained via voxel-wise subtraction of pre- and post- contrast QTI-derived T1 maps. ΔT1 values measured in ANELs were compared with those recorded in enhancing lesions and in the normal appearing white matter. A reference distribution of ΔT1 in the white matter was obtained from datasets acquired in 10 non-MS patients with unrevealing MR imaging. RESULTS: Mean ΔT1 in ANELs (57.45 ± 48.27 ms) was significantly lower than in enhancing lesions (297.71 ± 177.52 ms; p < 0. 0001) and higher than in the normal appearing white matter (36.57 ± 10.53 ms; p < 0.005). Fifty-two percent of ANELs exhibited ΔT1 higher than those observed in the white matter of non-MS patients. CONCLUSIONS: QTI-derived quantitative ΔT1 mapping enabled to measure contrast-related T1 shortening in ANELs. ANELs exhibiting ΔT1 values that deviate from the reference distribution in non-MS patients may indicate persistent, subtle, BBB disruption. Access to this information may be proved useful to better characterise pathology and objectively monitor disease activity and response to therapy.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Esclerose Múltipla/patologia , Meios de Contraste/metabolismo , Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
The present study evaluates the effect of exogenous melatonin (exo-MEL) on sleep and circadian parameters in patients with bipolar disorder (BD) and delayed sleep-wake phase disorder (DSWPD). BD euthymic patients (n = 83, mean age = 45.13 ± 13.68, males 56%) were evaluated for chronotype (reduced Morningness-Eveningness Questionnaire [rMEQ]), sleep quality (Pittsburgh Sleep Quality Index), sleep and circadian parameters (actigraphic monitoring). Patients that fulfilled criteria for DSWPD (n = 25) were treated for three months with exo-MEL 2 mg administered approximately 4 h before the sleep onset time (SOT) actigraphically-determined at baseline. Sleep and circadian parameters at baseline (T0) and after the exo-MEL treatment (T1) were compared using paired Wilcoxon test. In patients that completed the treatment (n = 19), the rMEQ score increased between T0 (median = 8.0 [IQR = 7.0, 11.0]) and T1 (median = 13.5 [IQR = 9.3, 15.0], p-value = 0.006), the SOT was advanced between T0 (median = 00:55 [IQR = 00:25, 01:39] and T1 (median = 00:09 [IQR = 23:41, 01:04], p-value = 0.039), the sleep efficiency and total sleep time increased (T0: median = 84.4 [IQR = 81.3, 89.4]; T1 (median = 90.3 [IQR = 85.5, 92.9] %, p-value = 0.01, and T0: median = 7.20 [IQR = 6.15, 8.15]; T1: median = 7.7 [IQR = 7.0, 9.3] hours, p-value = 0.04, respectively). These results indicate that in BD with comorbid DSWPD, the self-reported chronotype, the sleep onset time, and sleep efficiency and duration were modified after a personalized treatment with exo-MEL, suggesting its potential efficacy in improving sleep patterns in BD. The absence of proper control groups and of treatment randomization constitute limitations of our study and further randomized controlled trials are required to confirm our results.
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Transtorno Bipolar , Melatonina , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Melatonina/farmacologia , Melatonina/uso terapêutico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Sono , Ritmo Circadiano , ComorbidadeRESUMO
Interdisciplinary treatment is a widely implemented strategy for the rehabilitation of patients with chronic pain. A primary treatment objective is to decrease the load on the social insurance system; however, it is questionable whether interdisciplinary treatment reduces sickness absence and disability pension (SA/DP). This register-based observational study compared SA and DP between patients in interdisciplinary treatment and unspecified interventions. With data from 7,752 Swedish specialist health care patients in their prime working age, we analyzed total net SA/DP days over 3 years from the first visit to a pain rehabilitation center. A zero-one-inflated beta model, adjusted for theoretically substantiated confounders, was used to estimate the mean differences in total days and the proportions of patients with both zero and maximum days. Compared with unspecified interventions, interdisciplinary treatment resulted in a mean (95% confidence interval) absolute increase of 50 (37, 62) total days, a 13.0% (11.3%, 14.6%) decrease in patients with zero days, and a 1.5% (.2%, 2.8%) decrease in patients with the maximum days. These findings support that interdisciplinary treatment increases SA/DP compared to less intensive interventions but reduces the risk of maximum days, implying that it is advantageous for patients with the highest absence. This highlights the need for improved patient selection procedures and the adaptation of interdisciplinary treatment programs to more adequately target SA/DP reduction. PERSPECTIVES: This study provides an accessible overview of SA/DP among working-age patients with chronic pain in Swedish specialist health care. It also shows that interdisciplinary treatment does not decrease SA/DP more than alternative treatments in most patients but is advantageous for the patients with the longest absence.
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Dor Crônica , Pessoas com Deficiência , Humanos , Dor Crônica/terapia , Pensões , Fatores de Risco , Licença Médica , Suécia/epidemiologiaRESUMO
Mentation reports were collected after spontaneous awakenings from morning naps in 18 healthy participants, and associations between sleep stages duration and complexity of recalled mentation were investigated. Participants were continuously recorded with polysomnography and allowed to sleep for a maximum of 2 hr. Mentation reports were classified according to both their complexity (1-6 scale) and their perceived timing of occurrence (Recent or Previous Mentation with respect to the final awakening). The results showed a good level of mentation recall, including different types of mentation with lab-related stimuli. N1 + N2 duration was positively related to the complexity of Previous Mentation recall, while rapid eye movement sleep duration was negatively related. This suggests that the recall of complex mentation, such as dreaming with a plot, occurring far from awakening may depend on the length of N1 + N2. However, the duration of sleep stages did not predict the complexity of Recent Mentation recall. Nevertheless, 80% of participants who recalled Recent Mentation had a rapid eye movement sleep episode. Half of the participants reported incorporating lab-related stimuli in their mentation, which positively correlated with both N1 + N2 and rapid eye movement duration. In conclusion, nap sleep architecture is informative about the complexity of dreams perceived as having occurred early during the sleep episode, but not about those perceived as recent.
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Sonhos , Sono , Humanos , Rememoração Mental , Sono REM , Fases do SonoRESUMO
OBJECTIVE: Although the association between chronotype and mood disorders has been consistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chronotype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD). METHODS: Overall, 173 subjects, patients with BD in euthymic phase (n = 76) and HC (n = 97), were evaluated through the reduced Morningness-Eveningness Questionnaire (rMEQ), actigraphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ-based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI). RESULTS: rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS-SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only. CONCLUSION: Self-reported ET was consistently associated with mood symptoms, while associations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders.
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Transtorno Bipolar , Humanos , Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Cronotipo , Transtornos do Humor , Ansiedade , Afeto , Inquéritos e Questionários , Ritmo Circadiano , SonoRESUMO
The present study aimed at exploring whether lifetime post-traumatic stress spectrum symptoms are associated with chronotype in patients with bipolar disorder (BD). Moreover, we explored whether the chronotype can moderate the potential associations between lifetime post-traumatic stress spectrum symptoms and rest-activity circadian and sleep-related parameters. A total of 74 BD patients were administered the Trauma and Loss Spectrum Self-Report (TALS-SR) lifetime version for lifetime post-traumatic stress spectrum symptoms, the Pittsburgh Sleep Quality Index (PSQI) for self-reported sleep quality, and the Reduced Morningness-Eveningness Questionnaire (rMEQ) to discriminate evening chronotypes (ETs), neither chronotype (NT), and morning chronotype (MT). Actigraphic monitoring was used to objectively evaluate sleep and circadian parameters. Patients classified as ET reported significantly higher scores in the re-experiencing domain, as well as poorer sleep quality, lower sleep efficiency, increased wake after sleep onset, and delayed mid-sleep point compared with both NT and MT (p-value ≤ 0.05). Moreover, ET presented significantly higher scores in the TALS-SR maladaptive coping domain than NT and lower relative amplitude than MT (p-value ≤ 0.05). Moreover, higher TALS-SR total symptomatic domains scores were significantly correlated with poor self-reported sleep quality. Regression analyses showed that the PSQI score maintained the association with the TALS total symptomatic domains scores after adjusting for potentially confounding factors (age and sex) and that no interaction effect was observed between the chronotype and the PSQI. Conclusions: This exploratory study suggests that patients with BD classified as ET showed significantly higher lifetime post-traumatic stress spectrum symptoms and more disrupted sleep and circadian rhythmicity with respect to other chronotypes. Moreover, poorer self-reported sleep quality was significantly associated with lifetime post-traumatic stress spectrum symptoms. Further studies are required to confirm our results and to evaluate whether targeting sleep disturbances and eveningness can mitigate post-traumatic stress symptoms in BD.
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Transtorno Bipolar , Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Humanos , Sono , Ritmo Circadiano , Inquéritos e QuestionáriosRESUMO
MAIN OBJECTIVE: Sickness absence duration for shoulder lesion patients is difficult to prognosticate, and scientific evidence for the sick-listing practice is lacking. Our objective was to develop a clinically implementable prediction model for the duration of a sickness absence spell due to shoulder lesions. METHODS: All new sickness absence spells due to shoulder lesions (ICD-10-code: M75) issued in the period January 2010-June 2012 that were longer than 14 days were identified through the nationwide sickness absence insurance register. Information on predictors was linked from four other nationwide registers. Piecewise-constant hazards regression models were fitted to predict duration of sickness absence. The model was developed and validated using split sample validation. Variable selection was based on log-likelihood loss ranking when excluding a variable from the model. The model was evaluated using calibration plots and the c-statistic. RESULTS: 20 049 sickness absence spells were identified, of which 34% lasted >90 days. Predictors included in the model were age, sex, geographical region, occupational status, educational level, birth country, specialized healthcare at start of the spell, number of sickness absence days in the last 12 months, and specialized healthcare the last 12 months, before start date of the index sickness absence spell. The model was satisfactorily specified and calibrated. Overall c-statistic was 0.54 (95% CI 0.53-0.55). C-statistic for predicting durations >90, >180, and >365 days was 0.61, 0.66, and 0.74, respectively. SIGNIFICANCE: The model can be used to predict the duration of sickness absence due to shoulder lesions. Covariates had limited predictive power but could discriminate the very long sickness absence spells from the rest.
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Emprego , Ombro , Humanos , Prognóstico , Suécia/epidemiologia , Modelos de Riscos Proporcionais , Licença MédicaRESUMO
Adolescents' conflict between circadian rhythm and early school start time is more pronounced in evening chronotypes, who tend to reduce sleep duration during school days compensating during the free days by oversleeping (i.e., social jetlag). Cumulative weekly sleep debt may impair sport performance, which relies on physical and cognitive skills modulated by sleep. We hypothesized that chronotype predicts sport performance, and that it may interact with the day of the week. Moreover, given the role sleep plays in motor memory consolidation, we tested the hypothesis that school attendance, and the related chronic sleep deprivation, might be detrimental for participants in a training phase. Ninety-three adolescent male basketball players performed multiple free throw sessions (n = 7880) during both the school and holiday periods. Chronotype and its interaction with the day of the week significantly predicted shooting accuracy when attending school, but not on holidays. Evening types' performance gradually decreased from Monday to Friday. Participants with a more unstable performance (i.e., who did not complete the acquisition of the free throw motor scheme) worsened their accuracy when attending school. Our results suggest that the impact of chronotype and day of the week on sport performance is related to the presence of an externally imposed sleep/wake schedule and is consistent with evening types' increased likelihood of experiencing social jetlag. Possibly due to early school start time, attending school worsened the performance of participants in a training phase. Further investigations are required to assess whether reducing the mismatch between biological and social clocks might improve sport performance, along with other aspects of adolescents' life.
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Basquetebol , Ritmo Circadiano , Humanos , Masculino , Adolescente , Cronotipo , Sono , Síndrome do Jet Lag , Instituições Acadêmicas , Inquéritos e QuestionáriosRESUMO
Quantile regression permits describing how quantiles of a scalar response variable depend on a set of predictors. Because a unique definition of multivariate quantiles is lacking, extending quantile regression to multivariate responses is somewhat complicated. In this paper, we describe a simple approach based on a two-step procedure: in the first step, quantile regression is applied to each response separately; in the second step, the joint distribution of the signs of the residuals is modeled through multinomial regression. The described approach does not require a multidimensional definition of quantiles, and can be used to capture important features of a multivariate response and assess the effects of covariates on the correlation structure. We apply the proposed method to analyze two different datasets.
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We describe an estimating equation that can be used to fit quantile regression models to interval-censored data. The proposed estimator presents important advantages over the existing methods, and can be applied when the data are a mixture of interval-censored, left-censored, and right-censored observations. We describe estimation and inference, report simulation results, and apply the proposed method to analyze the Signal Tandmobiel® data. The necessary R code has been incorporated in the existing R package c t q r .
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Modelos Estatísticos , Simulação por ComputadorRESUMO
The study aims to investigate the association between different sleep management strategies and the final ranking during a one-night sailing race. A large sample of 190 teams participating in the overnight sailing regatta (151 Miglia) were included in the study. The experimental design consisted of two surveys, administered one before the start of the race and the other after the arrival. The questionnaires provided general information on the sailboat, its crew, and the strategy adopted to manage sleep during the race. In this one-night regatta, the self-management of sleep/wake timing emerged as the most successful strategy. Among participants who adopted a shift-based racing strategy, a short night shift duration (i.e., 2 h) significantly predicted a better placement. These findings confirmed the relevance of sleep management in sport performance and provided new insights into the most suitable sleep management strategy during a relatively short offshore regatta. The conclusions might apply also to similar continuous-cycle activities. Further investigations are needed to explore best sleep management strategy in team regattas of longer duration.
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Esportes , Tolerância ao Trabalho Programado , Humanos , Sono , Inquéritos e Questionários , Ritmo CircadianoRESUMO
BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous diagnostic category, encompassing several endophenotypes and comorbidities, including sleep problems. However, no predictor of clinical long-term trajectories or comorbidity has yet been established. Sleep EEG has been proposed as a potential tool for evaluating the synaptic strength during development, as well as the cortical thickness, which is presumed to be altered in ADHD. We investigated whether the slope of the Slow Waves (SWs), a microstructural parameter of the sleep EEG, was a potential predictive parameter for psychiatric comorbidities and neuropsychological dimensions in ADHD. METHODS: 70 children (58 m; 8.76 ± 2.77 y) with ADHD who underwent psychiatric and neurologic evaluations and a standard EEG recording during naps were investigated. After sleep EEG analysis, we grouped the extracted SWs in bins of equal amplitude and then measured the associations, through generalized linear regression, between their maximum downward slopes (MDS) and the individual scores obtained from clinical rating scales. RESULTS: The presence of Multiple Anxiety Disorders was positively associated with MDS of medium amplitude SWs in temporo-posterior left areas. The Child Behavior Checklist scores showed negative associations in the same areas for small SWs. The presence of autistic traits was positively associated with MDS of high amplitude SWs in bilateral anterior and temporal left areas. The WISC-IV Processing Speed Index showed negative associations with MDS of small-to-medium SWs in anterior and temporal right areas, while positive associations in posterior and temporal left areas. CONCLUSIONS: Consistency of association clusters' localization on the scalp suggests that variations in the local MDS, revealing alterations of local synaptic strength and/or in daytime use of certain cortical circuits, could underlie specific neurodevelopmental trajectories resulting in different ADHD clinical phenotypes.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , SonoRESUMO
BACKGROUND: Patterns of initiation and propagation of disease in Amyotrophic Lateral Sclerosis (ALS) are still partly unknown. Single or multiple foci of neurodegeneration followed by disease diffusion to contiguous or connected regions have been proposed as mechanisms underlying symptom occurrence. Here, we investigated cortical patterns of upper motor neuron (UMN) pathology in ALS using iron-sensitive MR imaging. METHODS: Signal intensity and magnetic susceptibility of the primary motor cortex (M1), which are associated with clinical UMN burden and neuroinflammation, were assessed in 78 ALS patients using respectively T2*-weighted images and Quantitative Susceptibility Maps. The signal intensity of the whole M1 and each of its functional regions was rated as normal or reduced, and the magnetic susceptibility of each M1 region was measured. RESULTS: The highest frequencies of T2* hypointensity were found in M1 regions associated with the body sites of symptom onset. Homologous M1 regions were both hypointense in 80-93 % of patients with cortical abnormalities, and magnetic susceptibility values measured in homologous M1 regions were strongly correlated with each other (ρ = 0.88; p < 0.0001). In some cases, the T2* hypointensity was detectable in two non-contiguous M1 regions but spared the cortex in between. CONCLUSIONS: M1 regions associated with the body site of onset are frequently affected at imaging. The simultaneous involvement of both homologous M1 regions is frequent, followed by that of adjacent regions; the affection of non-contiguous regions, instead, seems rare. This type of cortical involvement suggests the interhemispheric connections as one of the preferential paths for the UMN pathology diffusion in ALS.
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Esclerose Lateral Amiotrófica , Córtex Motor , Esclerose Lateral Amiotrófica/patologia , Humanos , Ferro , Imageamento por Ressonância Magnética/métodos , Neurônios Motores/patologiaRESUMO
BACKGROUND: Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E' and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. METHODS: EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. RESULTS: Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E' that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E' but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E' and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E', p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E' of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. CONCLUSION: Age and HTN have a synergic negative effect on E/E' and TAPSE at peak exercise in hypertensive subjects.