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Background: While functional connectivity is widely studied, there has been little work studying functional connectivity at different spatial scales. Likewise, the relationship of functional connec...

Mechanical Affective Touch Therapy (MATT) is a safe, novel form of noninvasive peripheral nerve stimulation. Although mechanical stimulation activates nerves, we know little about its impact on psychiatric symptoms and their underlying cortical mechanisms. We examined the effects of open-label MATT on resting state functional connectivity (RSFC) and its relationship with anxiety and affective symptomatology (clinical results in separate report).A total of 22 adults with an Axis I anxiety disorder were recruited from the community. After two initial sessions assisted by research staff, participants self-administered 20-minute sessions of MATT at home at least twice daily for four weeks. Self-report measures of mood and anxiety severity were collected at baseline, two weeks, and four weeks. Resting state functional magnetic resonance imaging was collected before the initial MATT session (n = 20), immediately after the first session (n = 18), and following four weeks of MATT (n = 14). Seed-based whole-brain functional connectivity analyses identified brain connectivity patterns correlated with responsiveness to MATT. Seeds were based on Neurosynth meta-analytic maps for "anxiety" and "pain" given MATT's hypothesized role in anxiety symptom amelioration and potential mechanism of action through C-tactile afferents, which play an important role in detecting pain and its affective components. Connectivity results were corrected for multiple comparisons (voxel p 0.005, cluster p-FDR 0.05).Baseline RSFC is predictive of symptom improvement with chronic MATT. Acute increases in insula connectivity were observed between mid-cingulate cortex and postcentral motor regions following the first MATT session. Chronic MATT was associated with increased connectivity between pain and anxiety regions of interest (ROIs) and posterior default mode network (DMN) regions involved in memory and self-reflection; the connectivity changes correlated with decreases in stress and depression symptoms.MATT is associated with alterations in RSFC in the DMN of anxiety disorder patients both acutely and after long-term administration, and baseline RSFC is predictive of post-treatment symptom improvement.

Internet addiction (IA) has become a global concern among college students. To explore the psychophysiological mechanism that is related to IA, this study investigated the role of resilience, loneliness, and resting respiratory sinus arrhythmia (RSA) in IA through a moderated mediation model. A group of 108 (

Abnormalities in cortical sources of resting-state eyes-closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10–20 electrode montage) with 19 scalp electrodes provide useful markers of neurophysiological dysfunctions in the vigilance regulation in patients with Alzheimer's disease dementia (ADD). Here we tested whether these markers may be effective from a few scalp electrodes towards the use of low-cost recording devices. Clinical and rsEEG data acquired in hospital settings (10–20 electrode montage) from 88 ADD participants and 68 age-, education-, and sex-matched normal elderly controls (Nold) were available in an international Eurasian database. Standard spectral FFT analysis of rsEEG data for individual delta, theta, and alpha frequency bands was from C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels. As compared to the Nold group, the ADD group showed increased delta, theta, low-frequency alpha power density and decreased high-frequency alpha power density at all those bipolar channels. The highest classification accuracy between the ADD and Nold individuals reached 90 % (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from a few posterior bipolar channels successfully classified Nold and ADD individuals, thus encouraging a massive prescreening of neurophysiological mechanisms underpinning the vigilance dysregulation in underserved old seniors. Ministero della Salute

Abnormalities in cortical sources of resting-state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10-20 montage) with 19 scalp electrodes characterized Alzheimer's disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluation of AD progression in large populations with few electrodes in low-cost devices. Here we evaluated whether the above-mentioned abnormalities can be observed from fewer scalp electrodes in patients with mild cognitive impairment due to AD (ADMCI). Clinical and rsEEG data acquired in hospital settings (10-20 montage) from 75 ADMCI participants and 70 age-, education-, and sex-matched normal elderly controls (Nold) were available in an Italian-Turkish archive (PDWAVES Consortium; www.pdwaves.eu ). Standard spectral fast fourier transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3-P3, C4-P4, P3-O1, and P4-O2 markers. The ADMCI group showed increased delta and decreased alpha power density at the C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels compared to the Nold group. Increased theta power density for ADMCI patients was observed only at the C3-P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from six posterior bipolar channels characterized ADMCI status. These results may pave the way toward diffuse clinical applications in health monitoring of dementia using low-cost EEG systems with a strict number of electrodes in lower- and middle-income countries.

Hostile attribution bias (HAB) has been considered as a risk factor of various types of psychosocial adjustment problem, and contributes to displaced aggression (DA). The neural basis of HAB and the underlying mechanisms of how HAB predicts DA remain unclear.The current study used degree centrality (DC) and resting-sate functional connectivity (RSFC) to investigate the functional connection pattern related to HAB in 503 undergraduate students. Furthermore, the "Decoding" was used to investigate which psychological components the maps of the RSFC-behavior may be related to. Finally, to investigate whether and how the RSFC pattern, HAB predicts DA, we performed mediation analyses.We found that HAB was negatively associated with DC in bilateral temporal poles (TP) and positively correlated with DC in the putamen and thalamus; Moreover, HAB was negatively associated with the strength of functional connectivity between TP and brain regions in the theory of mind network (ToM), and positively related to the strength of functional connectivity between the thalamus and regions in the ToM network. The "Decoding" showed the maps of the RSFC-behavior may involve the theory mind, autobiographic, language, comprehension and working memory. Mediation analysis further showed that HAB mediated the relationship between some neural correlates of the HAB and DA.The current results need to be further tested by experimental methods or longitudinal design in further studies.These findings shed light on the neural underpinnings of HAB and provide a possible mediation model regarding the relationships among RSFC pattern, HAB, and displaced aggression.

With the significant impact of Internet services and the evolution in the hardware and software fields, the Internet size and usage scope are continuously covering smaller and resource-constrained devices. Such devices, commonly called IoT devices, with sensing/actuation capabilities, are now capable of managing the complexity of communications over the Internet. However, considering the current IoT ecosystem, this field is still fragmented with respect to the communication technologies, protocols, and data formats used by the different providers. This heterogeneity makes IoT devices/systems unable to communicate seamlessly, leading to limited cooperation and tightly coupled deployments. To overwhelm the interoperability barriers in IoT, we propose, in this paper, a Cloud-based approach with a Dynamic Domain Name System (DDNS) mechanism enabling the IoT devices to communicate using the REST model. An approach that follows the Web of things (WoT) paradigm. In particular, the system enables the IoT devices' hosted resources (e.g., sensors and actuators) to be steered using globally resolvable (over the Internet) Uniform Resource Locators (URLs) even when deployed behind Network Address Translators (i.e., NATs). Besides, the solution considers security aspects related to data transmission by leveraging the use of HTTPS with a Dynamic machnism managing Domain Validation (DV) certificates.

BackgroundWhile neuroimaging has provided insights into the formation of episodic memories in relation to voluntary memory recall, less is known about neural mechanisms that cause memories to occur involuntarily, for example, as intrusive memories of trauma. Here, we investigated brain activity shortly after viewing distressing events as a function of whether memories for those events later intruded involuntarily. The postencoding period is particularly important because it is a period when clinical interventions could be applied.MethodsA total of 32 healthy volunteers underwent functional magnetic resonance imaging while viewing distressing film clips, interspersed with 5 minutes of awake (postencoding) rest. Voluntary memories of the films were assessed using free recall and verbal and visual recognition tests after a week, while intrusive (involuntary) memories were recorded in a diary throughout that week.ResultsWhen analyzing functional magnetic resonance imaging responses related to watching the films, we replicated findings that those “hotspots” (salient moments within the films) that would later become intrusive memories elicited higher activation in parts of the brain’s salience network. Surprisingly, while the postencoding persistence of multivoxel correlation structures associated with entire film clips predicted subsequent voluntary recall, there was no evidence that they predicted subsequent intrusions.ConclusionsResults replicate findings regarding the formation of intrusive memories during encoding and extend findings regarding the consolidation of information in postencoding rest in relation to voluntary memory. While we provided a first step using a naturalistic paradigm, further research is needed to elucidate the role of postencoding neural processes in the development of intrusive memories.

In this paper, the globally asymptotic synchronization of multi-layer neural networks is studied via aperiodically intermittent control. Due to the property of intermittent control, it is very hard to deal with the effect of time-varying delays and ascertain the control and rest widths for intermittent control. A new lemma with generalized Halanay-type inequalities are proposed first. Then, by constructing a new Lyapunov–Krasovskii functional and utilizing linear programming methods, several useful criteria are derived to ensure the multilayer neural networks achieve asymptotic synchronization. Moreover, an aperiodically intermittent control is designed, which has no direct relationship with control widths and rest widths and extends existing aperiodically intermittent control techniques, the control gains are designed by solving the linear programming. Finally, a numerical example is provided to confirm the effectiveness of the proposed theoretical results.

Objetivo: determinar en almendros cv. Guara y cv. Marinada la fecha de transición entre endodormancia y ecodormancia, y los requerimientos de frío y de calor para la salida del reposo otoño-invernal. Materiales y métodos: para determinar la fecha de transición entre endodormancia y ecodormancia, se utilizó un método de correlación entre la fecha de plena floración y períodos de temperatura media del aire. El requerimiento de frío se determinó mediante tres modelos distintos: horas de frío (HF), unidades de frío (UF) y porciones de frío (PF). La acumulación de calor se calculó como horas grado de crecimiento (GDH °C) para los tres modelos de acumulación de frío. Resultados: la fecha media de transición entre endodormancia y ecodormancia fue el 29 de julio para el cv. Guara y el 27 de julio para el cv. Marinada. El modelo de PF estimó la fecha de plena floración un día antes a la observada a campo. El modelo de HF seis días antes y el de UF seis días después. Conclusión: el modelo más adecuado fue el de PF. Los cultivares Guara y Marinada poseen el mismo requerimiento de frío (41 PF) y distinto requerimiento de calor (4626 y 5552 GDH ºC, respectivamente), para florecer Objective: determine in almond cv. Guara and cv. Marinada the date of transition between endodormancy and ecodormancy, and chill and heat requirements to breaking autumn-winter. Materials and methods: to determine the transition date between endodormancy and ecodormancy, a correlation method was used between the date of full bloom and periods of average air temperature. The cold requirement was determined using three different models: chill hours (CH), chill units (CU) and chill portions (CP). Heat accumulation was calculated as growing degree hours (GDH °C) for the three models of cold accumulation. Results: the average transition date between endodormancy and ecodormancy was July 29 for cv. Guara and July 27 for cv. Marinada. The CP model estimated the date of full bloom one day before that observed in the field. The CH model six days earlier, and the CU model six days later. Conclusion: the most suitable model was the CP model. Cultivars Guara and Marinada have the same cold requirement (41 CP) and different heat requirements (4626 and 5552 GDH ºC, respectively), for blooming. EEA Mendoza Fil: Chaar, Javier Emilio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Agencia de Extensión Rural Guaymallén; Argentina Fil: Castro, Viviana Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; Argentina

Essential tremor (ET) is characterized by action tremor, although rest tremor may also occur. Despite this, rest tremor has not been studied extensively. A dearth of studies compare the relationship of rest tremor to other types of tremors in ET.Two-hundred-and-thirteen ET cases underwent detailed neurological examination, including evaluations of rest, simple kinetic, postural, and intention tremors. A movement disorders neurologist assessed the prevalence of each type of tremor. Each instance of tremor was classified as either symmetrical (present and equally severe on both sides of the body) or asymmetrical (only present on or more severe on one side of the body). Asymmetrical rest tremor that co-occurred with other types of asymmetrical tremors in a given case was further classified as either concordant (i.e., asymmetry on the same side of the body) or discordant (i.e., asymmetry on opposite sides of the body). Chi-square analyses examined the prevalence of concordant versus discordant pairings.Sixty-two cases (29.2%) had rest tremor while seated. Fifteen (7.4%) had rest tremor while standing. Among asymmetric tremor pairings, concordant pairings occurred 2-2.7 times more frequently than discordant pairings - for pairings involving rest tremor while seated, 73.2% were concordant and 26.8% discordant (p 0.001); for pairings involving rest tremor while standing, 66.7% were concordant and 33.3% were discordant (p = 0.25).Rest tremor often lateralized with other tremor types. These data add to our knowledge of the phenotypic manifestations of ET.

Le présent article vise à présenter les conventions communes à la construction des API REST. Elle est issue d’un ensemble de bonnes pratiques communément appliquées et d’expériences accumulées sur la création des API REST.

Le présent article vise à présenter les conventions communes à la construction des API REST. Elle est issue d’un ensemble de bonnes pratiques communément appliquées et d’expériences accumulées sur la création des API REST.

Introduction: The recovery interval (RI) between sets and exercises has received attention from strength training (ST) researchers, to understand the relationship of rest on performance maintenance, especially the total load in a training session. It is known that each individual responds in a specific way to the training stimulus. So, what would be the effect of the different recovery interval strategies on the strength performance? Objective: Compare the different recovery intervals in strength training volume, considering the number of repetitions in healthy adults. Methods: We conducted a systematic review and meta-analysis based on methodological criteria, comparing fixed and self-selected RI on training volume, identified by the number of repetitions performed in a weight training program. Three electronic databases (Pubmed, VHL Virtual Health Library, Ebsco Sportdiscus) were analyzed, combining the expressions “resistance training”, “resistance exercise”, “strength exercise”, “recovery interval”, “rest interval”, “interval auto suggested”, “auto range selected” with “AND” and “OR” combination. Results: Pooled data from five studies showed a large significant effect in favor of the experimental group (>2 minutes) (MD: 1.24; 95%-CI [0.78; 1.71]; z: 5.25, Q:1.08; p < 0.01), since in the studies, recovery interval allowed a greater training volume. Conclusion: Longer RI seems be better, for maintaining total training volume, although there is no consensus for different training objectives against the self-selected RI. Thus, we imagine that this strategy may be important in the organizing a bodybuilding exercise program. Level of Evidence I; Systematic Review and Meta Analysis. RESUMEN Introducción: El intervalo de recuperación (IR) entre series y ejercicios ha recibido atención por parte de los investigadores del entrenamiento de fuerza (EF), contribuyendo a la comprensión de esta variable en relación con el mantenimiento del rendimiento, especialmente la carga durante el entrenamiento con pesas. Se sabe que cada individuo responde de manera específica al estímulo del entrenamiento, entonces, ¿cuál es el efecto de las diferentes estrategias de intervalos de recuperación sobre el rendimiento de fuerza? Objetivo: Comparar diferentes intervalos de recuperación en entrenamiento de fuerza en volumen de entrenamiento, identificados por el número de repeticiones en musculación en adultos sanos. Métodos: Realizamos una revisión sistemática y un metanálisis basado en criterios metodológicos, comparando IR fijo y autoseleccionado en función del volumen de entrenamiento, identificado por el número de repeticiones realizadas en un programa de entrenamiento con pesas. Se analizaron los registros de tres bases de datos electrónicas (Pubmed, Biblioteca Virtual en Salud de la BVS, Ebsco Sportdiscus), combinando las palabras “entrenamiento de resistencia”, “ejercicio de resistencia”, “ejercicio de fuerza”, “intervalo de recuperación”, “intervalo de descanso”, “intervalo auto sugerido”, “rango automático seleccionado” con la combinación “AND” y “OR”. Resultados: Los datos agrupados de cinco estudios mostraron un gran efecto significativo a favor del grupo experimental (> 2 minutos) (DM: 1,24; IC del 95 % [0,78; 1,71]; z: 5,25, Q: 1,08; p < 0,01), ya que, en los estudios en cuestión, este intervalo de recuperación permitió un mayor volumen de entrenamiento. Conclusión: Los intervalos más largos parecen ser mejores, en el volumen total de entrenamiento, aunque no hay consenso para diferentes objetivos de entrenamiento frente al RI autoseleccionado. Por lo tanto, imaginamos que esta estrategia puede ser importante en la organización del programa de ejercicios de musculación. Nivel de Evidencia I; Revisión Sistemática y Meta Análisis. RESUMO Introdução: O intervalo de recuperação (IR) entre séries e exercícios, tem recebido atenção dos pesquisadores de treinamento de força (TF), contribuindo no entendimento dessa variável em relação a manutenção do rendimento, em especial da carga durante o treinamento de musculação. Sabe-se que cada indivíduo responde de modo específico ao estimulo do treinamento, desta forma, qual o efeito das diferentes estratégias do intervalo recuperação no desempenho da força? Objetivo: Comparar diferentes intervalos de recuperação no treinamento de força no volume de treino, identificado pelo número de repetições na musculação em adultos saudáveis. Métodos: Realizamos, pelos critérios metodológicos, revisão sistemática e meta-análise, comparando o IR fixo e auto selecionado em função do volume de treino, identificado pelo número de repetições realizados em programa de musculação. Foram analisados os registros de três bases de dados eletrônicas (Pubmed, Biblioteca Virtual da Saúde BVS, Ebsco Sportdiscus), combinando as expressões “treinamento de resistência”, “exercício resistido”, “exercício de força”, “intervalo de recuperação”, “intervalo de descanso”, “intervalo auto sugerido”, “intervalo auto selecionado” com combinação “AND” e “OR”. Resultados: Os dados reunidos de cinco estudos mostraram um grande efeito significante a favor do grupo experimental (>2 minutos) (MD: 1.24; 95%-IC [0.78; 1.71]; z: 5.25, Q:1.08; p < 0.01), uma vez que nos estudos em questão, esse intervalo de recuperação possibilitou maior volume de treino. Conclusão: Intervalos mais longos parecem ser melhores no volume total do treinamento, embora não haja consenso para diferentes objetivos do treinamento frente ao IR auto selecionado. Dessa forma, imaginamos que essa estratégia possa ser importante na organização do programa de exercício de musculação. Nível de Evidencia I; Revisão Sistemática e Meta Análise.

Down syndrome (DS) is the most frequently diagnosed chromosomal disorder of chromosome 21 (HSA21) aneuploidy, characterized by intellectual disability and reduced lifespan. The transcription repressor, Repressor Element-1 Silencing Transcription factor (REST), which acts as an epigenetic regulator, is a crucial regulator of neuronal and glial gene expression. In this study, we identified and investigated the role of REST-target genes in human brain tissues, cerebral organoids, and neural cells in Down syndrome. Gene expression datasets generated from healthy controls and DS samples of human brain tissues, cerebral organoids, NPC, neurons, and astrocytes were retrieved from the Gene Ontology (GEO) and Sequence Read Archive (SRA) databases. Differential expression analysis was performed on all datasets to produce differential expression genes (DEGs) between DS and control groups. REST-targeted DEGs were subjected to functional ontologies, pathways, and network analyses. We found that REST-targeted DEGs in DS were enriched for the JAK–STAT and HIF-1 signaling pathways across multiple distinct brain regions, ages, and neural cell types. We also identified REST-targeted DEGs involved in nervous system development, cell differentiation, fatty acid metabolism and inflammation in the DS brain. Based on the findings, we propose REST as the critical regulator and a promising therapeutic target to modulate homeostatic gene expression in the DS brain.

Dysconnectivity of large-scale brain networks has been linked to major depression disorder (MDD) during resting state. Recent researches show that the temporal evolution of brain networks regulated by oscillations reveals novel mechanisms and neural characteristics of MDD. Our study applied a novel coupled tensor decomposition model to investigate the dysconnectivity networks characterized by spatio-temporal-spectral modes of covariation in MDD using resting electroencephalography. The phase lag index is used to calculate the functional connectivity within each time window at each frequency bin. Then, two adjacency tensors with the dimension of time frequency connectivity subject are constructed for the healthy group and the major depression group. We assume that the two groups share the same features for group similarity and retain individual characteristics for group differences. Considering that the constructed tensors are nonnegative and the components in spectral and adjacency modes are partially consistent among the two groups, we formulate a double-coupled nonnegative tensor decomposition model. To reduce computational complexity, we introduce the lowrank approximation. Then, the fast hierarchical alternative least squares algorithm is applied for model optimization. After clustering analysis, we summarize four oscillatory networks characterizing the healthy group and four oscillatory networks characterizing the major depression group, respectively. The proposed model may reveal novel mechanisms of pathoconnectomics in MDD during rest, and it can be easily extended to other psychiatric disorders. peerReviewed

Bipolar disorder (BD) is increasingly being regarded as a dysconnection syndrome. Functional integration among the three core brain networks - executive control network (ECN), salience network (SN), and default mode network (DMN) - is abnormal in patients with BD; however, the causal relationship among the three networks in BD is largely unknown. It is also unclear whether patients with BD in different mood states show distinct effective connectivity patterns during rest.Resting-state fMRI data were collected from 65 patients with BD and 85 healthy controls. Spectral dynamic causal modeling was applied to investigate the effective connectivity difference of the three brain networks between all patients with BD and healthy controls and between patients who were in euthymic mood state (euthymic BD) and depressed mood state (depressed BD).Compared with healthy controls, all patients with BD showed altered effective connectivity within and between the ECN and SN and from these two networks to the DMN. Compared with patients with depressed BD, patients with euthymic BD showed increased excitatory effects within the ECN and decreased inhibitory effects from the SN to the ECN and DMN.These results further confirmed that patients with BD show abnormal functional integration within and among the three core brain networks, and exhibit similar and different effective connectivity patterns in different mood states. Abnormal effective connectivity has the potential to be a critical index for diagnosing BD and differentiating between BD patients with different mood states.

Research on the electroencephalographic (EEG) signatures of attention-deficit/hyperactivity disorder (ADHD) has historically concentrated on its frequency spectrum or event-related evoked potentials. In this work, we investigate EEG microstates (MSs), an alternative framework defined by the clustering of recurring topographical patterns, as a novel approach for examining large-scale cortical dynamics in ADHD.Using k-means clustering, we studied the spatiotemporal dynamics of ADHD during the rest condition by comparing the MS segmentations between adult patients with ADHD and neurotypical control subjects across two independent datasets: the first dataset consisted of 66 patients with ADHD and 66 control subjects, and the second dataset comprised 22 patients with ADHD and 22 control subjects and was used for out-of-sample validation.Spatially, patients with ADHD and control subjects displayed equivalent MS topographies (canonical maps), indicating the preservation of prototypical EEG generators in patients with ADHD. However, this concordance was accompanied by significant differences in temporal dynamics. At the group level, and across both datasets, ADHD diagnosis was associated with longer mean durations of a frontocentral topography (MS D), indicating that its electrocortical generator(s) could be acting as pronounced attractors of global cortical dynamics. In addition, its spatiotemporal metrics were correlated with sleep disturbance, the latter being known to have a strong relationship with ADHD. Finally, in the first (larger) dataset, we also found evidence of decreased time coverage and mean duration of a left-right diagonal topography (MS A), which inversely correlated with ADHD scores.Overall, our study underlines the value of EEG MSs as promising functional biomarkers for ADHD, offering an additional lens through which to examine its neurophysiological mechanisms.

MicroRNAs (miRNAs) regulate molecular processes governing muscle metabolism. Physical activity and energy balance influence both muscle anabolism and substrate metabolism, but whether circulating and skeletal muscle miRNAs mediate those effects remains unknown. This study assessed the impact of sustained physical activity with participants in energy balance (BAL) or deficit (DEF) on circulating and skeletal muscle miRNAs. Using a randomized cross-over design, 10 recreational active healthy males (mean ± SD, 22 ± 5 years, 87 ± 11 kg) completed 72 h of high aerobic exercise-induced energy expenditures in BAL (689 ± 852 kcal/day) or DEF (-2047 ± 920 kcal/day). Blood and muscle samples were collected under rested/fasted conditions before (PRE) and immediately after 120 min load carriage exercise bout at the end (POST) of the 72 h. Trials were separated by 7 days. Circulating and skeletal muscle miRNAs were measured using microarray RT-qPCR. Independent of energy status, 36 circulating miRNAs decreased (P 0.05), while 10 miRNAs increased and three miRNAs decreased in skeletal muscle (P 0.05) at POST compared to PRE. Of these, miR-122-5p, miR-221-3p, miR-222-3p and miR-24-3p decreased in circulation and increased in skeletal muscle. Two circulating (miR-145-5p and miR-193a-5p) and four skeletal muscle (miR-21-5p, miR-372-3p, miR-34a-5p and miR-9-5p) miRNAs had time-by-treatment effects (P 0.05). These data suggest that changes in miRNA profiles are more sensitive to increased physical activity compared to energy status, and that changes in circulating miRNAs in response to high levels of daily aerobic exercise are not reflective of changes in skeletal muscle miRNAs. KEY POINTS: Circulating and skeletal muscle miRNA profiles are more sensitive to high levels of aerobic exercise-induced energy expenditure compared to energy status. Changes in circulating miRNA in response to high levels of daily sustained aerobic exercise are not reflective of changes in skeletal muscle miRNA.

Background: It is unknown how different pitch count limits and rest day requirements affect cumulative pitch counts during a baseball season. Purpose: To determine (1) the variability of pitch count rules in high school baseball and (2) the theoretical effect of different pitch count limits and rest day combinations on game, weekly, and seasonal pitch totals in high school baseball pitchers. Study Design: Cross-sectional study. Methods: Pitch count rules for the 2019-2020 academic year for 48 sanctioned states were recorded from each state’s athletic association website. Maximum pitch count limits were recorded along with the number of pitches allowed before requiring 0 to 5 rest days before the next pitching outing. Rules were also analyzed for several distinctions, including the athlete’s level of competition, age, and grade. To determine the effect of pitch count rules and rest days, a theoretical 3-month season was calculated in the following scenarios: (1) variable maximum pitch count limits with a universal 3-day rest requirement, (2) universal 110 pitch count limit with variable rest day requirements (3, 4, or 5 days), and (3) actual pitch count limits and required rest days for every state assuming pitchers throw as many pitches as allowed. Analysis of variance and Student t tests were used to compare between-group and intragroup seasonal pitch totals based on variations in required rest days. Results: The most common maximum pitch count limit for a varsity high school athlete was 110 pitches (range, 100-125 pitches) with 4 rest days (range, 0-5 days). We found that 23 states (48%) did not make distinctions for pitch count rules based on the athlete’s level of competition, age, or grade. We noted a 25% increase in total seasonal pitch counts between the smallest and largest pitch count limit when assuming constant 3-day rest. We found a 53% difference in total seasonal pitch count when rest days varied between 3 and 5 days with a constant 110-pitch limit. Allowing 140 pitches in a 4-day span without a specific rest day requirement resulted in the highest seasonal pitch count (Nevada). There was a 49% difference in maximum seasonal pitch counts between the most and least restrictive states ( P < .001). Submaximum pitch limits resulted in higher seasonal pitch counts than maximum pitch limits in 56% of states. Conclusion: Pitch count rules vary widely by state. Required rest days influenced total seasonal pitch counts more than maximum or submaximum pitch count limits.

The primary aim of this narrative review was to outline the historical genesis of resistance training strategies that incorporate high-load, low-velocity exercises and low-load, high-velocity exercises in the same training session allowing for different "exercise sequences" to be simultaneously implemented. Discrepancies between scientific works and the terminology used within contemporary sport science publications are identified. Upon review of the literature, we propose "complex training" to be considered an umbrella term with 4 different implementations, generally used to indicate a method in which movement velocity or load is altered between sets and/or exercises within the same session with the aim of improving slow and fast force expression. We propose the following terminology for said implementations: contrast training-exercise sequence with alternating high-load and low-load (higher-velocity) exercises in a set-by-set fashion within the same session (corresponding with 'contrast pairs' and 'intra-contrast rest'); descending training-several sets of high-load (e.g., back squat) exercises completed before the execution of several sets of low-load, higher-velocity (e.g., vertical jump) exercises within the same session; ascending training-several sets of low-load, higher-velocity exercises completed before several sets of high-load exercises within the same session; and French contrast training-subset of contrast training in which a series of exercises are performed in sequence within a single session: heavy compound exercise, plyometric exercise, light-to-moderate load compound exercise that maximises movement speed (i.e., external power), and a plyometric exercise (often assisted). Finally, practical applications and training considerations are presented.

Finding the baseline resting-state EEG markers for early identification of cognitive decline can contribute to the identification of individuals at risk of further change. Potential applications include identifying participants for clinical trials, early treatment, and evaluation of treatment, accessible even from a community setting.Analyses were completed on a sample of 99 (ages 60-90) consensus-diagnosed, community-dwelling African Americans (58 cognitively typical/HC, and 41 mildly cognitively impaired/MCI), who were recruited from the Michigan Alzheimer's Disease Research Center (MADRC) and the Wayne State University Institute of Gerontology. In addition to neuropsychological testing with CogState and Toolbox computerized batteries, resting-state EEGs (rsEEG, eyes closed) were acquired before and after participants were engaged in a visual motion direction discrimination task. rsEEG frontal alpha asymmetry (FAA) and frontal beta asymmetry (FBA) were calculated.FAA showed no difference across groups for the pre-task resting state. FBA was significantly different between groups, with more asymmetric frontal beta in MCI. Both physiological indices, however, along with computerized neuropsychological tests were significant predictors in logistic regression classification of MCI vs. control participants.rsEEG asymmetries can contribute significantly to successful discrimination of older persons with MCI from those without, over and above cognitive testing, alone.

Web services often impose inter-parameter dependencies that restrict the way in which two or more input parameters can be combined to form valid calls to the service. Unfortunately, current specification languages for web services like the OpenAPI Specification (OAS) provide no support for the formal description of such dependencies, which makes it hardly possible to automatically discover and interact with services without human intervention. In this article, we present an approach for the specification and automated analysis of inter-parameter dependencies in web APIs. We first present a domain-specific language, called Inter-parameter Dependency Language (IDL), for the specification of dependencies among input parameters in web services. Then, we propose a mapping to translate an IDL document into a constraint satisfaction problem (CSP), enabling the automated analysis of IDL specifications using standard CSP-based reasoning operations. Specifically, we present a catalogue of nine analysis operations on IDL documents allowing to compute, for example, whether a given request satisfies all the dependencies of the service. Finally, we present a tool suite including an editor, a parser, an OAS extension, a constraint programming-aided library, and a test suite supporting IDL specifications and their analyses. Together, these contributions pave the way for a new range of specification-driven applications in areas such as code generation and testing. Junta de Andalucía US-1264651 Ministerio de Ciencia, Innovación y Universidades RTI2018-101204-B-C21 Ministerio de Educación y Formación Profesional FPU17/04077

White matter lesions (WMLs) are common in older adults and represent an important predictor of negative long-term outcomes. Rest-activity rhythm disturbance is also common, however, few studies have investigated associations between these factors. We employed a novel AI-based automatic WML segmentation tool and diffusion-weighted tractography to investigate associations between tract specific WML volumes and non-parametric actigraphy measures in older adults at risk for cognitive decline. The primary non-parametric measures of interest were inter-daily stability (IS), intra-daily variability and relative amplitude, with the anterior thalamic radiation (ATR), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) selected as tracts of interest. One hundred and eight participants at risk for cognitive decline (classified as experiencing subjective or objective cognitive decline) were included (mean age = 68.85 years, SD = 8.91). Of the primary non-parametric measures of interest, results showed that lower IS was associated with a greater likelihood of higher WML burden in the ATR (OR = 1.82, 95% CI [1.12,3.15]). Analysis of secondary non-parametric measures revealed later onset of the least active period to be associated with greater likelihood of high WML burden in the SLF (OR = 1.55, 95% CI [1.00,2.53]) and increased activity during the least active 5-h period to be associated with a greater likelihood of high whole-brain WML burden (OR = 1.83, 95% CI [1.06,3.47]). This study shows integrity of the ATR and SLF, and overall WML burden is linked to altered rest-activity rhythms in older adults at risk for cognitive decline, with those demonstrating altered rest-activity rhythms showing 50%-80% higher odds of having high WML burden.

Purpose To investigate the influence of shorter, more frequent rest breaks during simulated work (outdoor mining) in the heat on physical performance and psychophysiological responses. Methods On separate days, thirteen males undertook two 225 min simulation trials in the afternoon (12.00–3.45 pm) including 180 min of treadmill walking at a constant rate of perceived exertion of 11 (or ‘light’) on the 6–20 Borg scale in a heat chamber (37 °C, 40% RH), interspersed with 45 min of rest breaks in an air-conditioned room (22 °C, 35% RH). Rest breaks in the current practice (CP) trial occurred at 1.00 and 2.30 pm (30 min and 15 min, respectively), while in the experimental (EXP) trial were at 1.00 (15 min), 1.45, 2.25 and 3.05 pm (10 min each). Results Total distance covered was not different (p = 0.086) between CP (12,858 ± 2207 m) and EXP (12,094 ± 2174 m). Heart rate, thermal sensation and thermal comfort were significantly higher at 120–180 min (all p g = 0.50 and 0.99, respectively). No differences were found between trials for cognitive performance, perceived fatigue, urine specific gravity, or total water intake (p > 0.05). Conclusion Shorter, more frequent rest breaks have little impact on physical performance, thermal strain and exercise-related sensations. Current practices should remain in place until further studies can be conducted on an actual mine site during summer where outdoor workers perform their work duties.

Growing evidence suggests that impairment in rest-activity rhythms may be a risk factor for cognitive decline and impairment in the aging population. However, previous studies included only a limited set of rest-activity metrics and produced mixed findings. We studied a comprehensive set of parametric and nonparametric characteristics of rest-activity rhythms in relation to mild cognitive impairment (MCI) and probable dementia in a cohort of older women.The prospective analysis included 763 women enrolled in two ancillary studies of the Women's Health Initiative (WHI): the WHI Memory Study-Epidemiology of Cognitive Health Outcomes and Objective Physical Activity and Cardiovascular Health studies. The association between accelerometry-based rest-activity parameters and centrally adjudicated MCI and probable dementia were determined using Cox regression models adjusted for sociodemographic characteristics, lifestyle factors, and comorbidities.Overall, the results support a prospective association between weakened rest-activity rhythms (e.g., reduced amplitude and overall rhythmicity) and adverse cognitive outcomes. Specifically, reduced overall rhythmicity (pseudo F statistic), lower amplitude and activity level (amplitude/relative amplitude, mesor, and activity level during active periods of the day [M10]), and later activity timing (acrophase and midpoint of M10) were associated with a higher risk for MCI and probable dementia. Women with lower amplitude and mesor also exhibited faster cognitive decline over follow-up.Weakened rest-activity rhythms may be predictive markers for cognitive decline, MCI, and dementia among older women.

Although repetitive transcranial magnetic stimulation (rTMS) has exhibited promising efficacy in treating stroke-related aphasia, changes in neuroimaging in response to this therapy remain unclear.By using resting-state functional magnetic resonance imaging (rsfMRI), we examined brain activations associated with language recovery in patients with poststroke nonfluent aphasia during an rTMS intervention. Twenty-six stroke patients with nonfluent aphasia were recruited in this randomized double-blinded study. The patients received real (n = 13) or sham (n = 13) 1-Hz inhibitory rTMS to the right pars triangularis (PTr) for ten consecutive weekdays. They underwent rsfMRI and completed the Concise Chinese Aphasia Test (CCAT) before and after the rTMS intervention.The fractional amplitude of low-frequency fluctuation (fALFF) was calculated to investigate spontaneous neural activity in the brain. After treatment, the language function in the experimental group was higher than that in the sham group in terms of total CCAT score (p = 0.014) and the CCAT subscores of conversation (p = 0.012), description (p = 0.006), and expression (p = 0.003). Postintervention intergroup comparisons revealed that fALFF was significantly increased in the right superior temporal gyrus, right dorsolateral prefrontal gyrus, insular cortex, and caudate nucleus. Clusters in the right thalamus exhibited suppressed fALFF. The enhanced clusters in the frontotemporal region were significantly correlated with CCAT score improvements.Our findings provide empirical evidence for the vital role of the right frontotemporal and subcortical regions in language recovery after rTMS interventions in patients with aphasia. Inhibitory rTMS may improve language expression by promoting involvement of the right frontotemporal region. The results can be further used to refine rTMS protocols and optimize brain stimulation treatments.The Clinicaltrials.gov registration number for the study is NCT03059225.

Sammito, Stefan, David Cyrol, and Janina Post. Fatigue and ability to concentrate in flight attendants during ultra-long-range flights.

Purpose:The aim of this study was to investigate physiological responses and energetic contributions during simulated epée matches in elite fencers.Methods:Ten elite male fencers participated in simulated epée (direct elimination) matches. Simulated epée matches included 3 bouts of 3 minutes each with 1-minute rests between bouts. During these sessions, physiological variables such as mean and peak heart rate, peak and mean oxygen uptake (VO2peak and VO2mean), metabolic equivalents of task in VO2peak and VO2mean, and blood lactate concentrations (peak lactate concentration and delta blood lactate concentration) were measured. Furthermore, energetic contributions (oxidative [WOxi], glycolytic, and phosphagen) and time–motion variables were estimated.Results:Values of peak heart rate, mean heart rate, and WOxi(in percentages) were significantly higher in the second and third bouts compared with the first. VO2peak and metabolic equivalents of task in VO2peak were significantly higher in the first bout compared with the third bout. Values of delta blood lactate concentration and glycolytic contribution (in kilojoules and percentages) were significantly lower in the second and third bouts compared with the first. VO2mean and metabolic equivalents of task in VO2mean were significantly higher in the second bout compared with the third bout. Furthermore, WOxi(in kilojoules and percentage) was significantly higher in all bouts compared with phosphagen and glycolytic contributions. Low positive and negative correlations were seen between WOxi, VO2mean, sum of attacks and defense times, and the sum of time without attacks and defenses.Conclusions:Direct-elimination epée matches consist of high-intensity intermittent exercise, and the oxidative contribution is 80% to 90%. Improving aerobic conditioning may support high-intensity intermittent actions during entire epée matches in elite fencers.

Presentation given for the FAIR Digital Object Forum webinar on 2023-05-27. The presentation aims to clarify the relationship between FAIR Digital Objects and FAIR Signposting. A relationship that may not be obvious because Signposting does not start from an abstract model but rather from a very concrete problem related to how research objects exist on the web.

Cilj diplomskega dela je izdelati hitro, varno in uporabniku prijazno spletno trgovino ter aplikacijo za upravljanje vsebin s sodobnimi tehnologijami, ki se uporabljajo pri razvoju enostranskih spletnih aplikacij. Aplikaciji pridobivata in posodabljata podatke preko skupnega aplikacijskega programskega vmesnika - API, izdelanega s pomočjo tehnologije Node.js in Express.js ter nerelacijske podatkovne baze MongoDB. Aplikacija za upravljanje vsebin je razvita s pomočjo odprtokodne knjižnice React.js in je namenjena upravitelju spletne trgovine, ki ima možnost upravljanja s podatki v spletni trgovini. Spletna trgovina je razvita z ogrodjem Next.js in kupcem omogoča hiter ter varen nakup izdelkov preko spleta, z možnostjo plačila s kreditno kartico. Izdelane aplikacije zadostujejo vsem zahtevam, ki sem si jih zadal na začetku razvoja in imajo še veliko možnosti za izboljšave. The goal of the thesis is to create a fast, secure, and user-friendly webstore and a content management application using modern technologies commonly used in the development of single-page web applications. The applications obtain and update data through a common application programming interface (API) created using Node.js and Express.js, as well as a non-relational MongoDB database. The content management application is developed using the open-source React.js library and is intended for the webstore manager, who has the ability to manage the website's data. The webstore is developed using the Next.js framework and allows customers to quickly and safely purchase products online, including the option to pay by credit card. The developed applications meet all the requirements I set at the beginning of the development and have many opportunities for improvements.

RESTful Web API adoption has become ubiquitous with the proliferation of REST APIs in almost all domains with modern web applications embracing the micro-service architecture. This vibrant and expanding adoption of APIs, has made an increasing amount of data to be funneled through systems which require proper access management to ensure that web assets are secured. A RESTful API provides data using the HTTP protocol over the network, interacting with databases and other services and must preserve its security properties. Currently, practitioners are facing two major challenges for developing high quality secure RESTful APIs. One, REST is not a protocol. Instead, it is a set of guidelines that define how web resources can be designed and accessed over HTTP endpoints. There are a set of guidelines which stipulate how related resources should be structured using hierarchical URIs as well as how specific well-defined actions on those resources should be represented using different HTTP verbs. Whereas security has always been critical in the design of RESTful APIs, there are no clear formal models utilizing a secure-by-design approach that interweaves both the functional and security requirements. The other challenge is how to effectively utilize a model driven approach for constructing precise requirements and design specifications so that the security of a RESTFul API is considered as a concern that transcends across functionality rather than individual isolated operations.This thesis proposes a novel technique that encourages a model driven approach to specifying and verifying APIs functional and security requirements with the practical formal method SOFL (Structured-Object-Oriented Formal Language). Our proposed approach provides a generic 6 step model driven approach for designing security aware APIs by utilizing concepts of domain models, domain primitives, Ecore metamodel and SOFL. The first step involves generating a flat file with APIs resource listings. In this step, we extract resource definitions from an input RESTful API documentation written in RAML using an existing RAML parser. The output of this step is a flat file representing API resources as defined in the RAML input file. This step is fully automated. The second step involves automatic construction of an API resource graph that will work as a blue print for creating the target API domain model. The input for this step is the flat file generated from step 1 and the output is a directed graph (digraph) of API resource. We leverage on an algorithm which we created that takes a list of lists of API resource nodes and the defined API root resource node as an input, and constructs a digraph highlighting all the API resources as an output. In step 3, we use the generated digraph as a guide to manually define the API’s initial domain model as the target output with an aggregate root corresponding to the root node of the input digraph and the rest of the nodes corresponding to domain model entities. In actual sense, the generated digraph in step 2 is a barebone representation of the target domain model, but what is missing in the domain model at this stage in the distinction between containment and reference relationship between entities. The resulting domain model describes the entire ecosystem of the modeled API in the form of Domain Driven Design Concepts of aggregates, aggregate root, entities, entity relationships, value objects and aggregate boundaries. The fourth step, which takes our newly defined domain model as input, involves a threat modeling process using Attack Defense Trees (ADTrees) to identify potential security vulnerabilities in our API domain model and their countermeasures. aCountermeasures that can enforce secure constructs on the attributes and behavior of their associated domain entities are modeled as domain primitives. Domain primitives are distilled versions of value objects with proper invariants. These invariants enforce security constraints on the behavior of their associated entities in our API domain model. The output of this step is a complete refined domain model with additional security invariants from the threat modeling process defined as domain primitives in the refined domain model. This fourth step achieves our first interweaving of functional and security requirements in an implicit manner. The fifth step involves creating an Ecore metamodel that describes the structure of our API domain model. In this step, we rely on the refined domain model as input and create an Ecore metamodel that our refined domain model corresponds to, as an output. Specifically, this step encompasses structural modeling of our target RESTful API. The structural model describes the possible resource types, their attributes, and relations as well as their interface and representations. The sixth and the final step involves behavioral modeling. The input for this step is an Ecore metamodel from step 5 and the output is formal security aware RESTful API specifications in SOFL language. Our goal here is to define RESTful API behaviors that consist of actions corresponding to their respective HTTP verbs i.e., GET, POST, PUT, DELETE and PATCH. For example, CreateAction creates a new resource, an UpdateAction provides the capability to change the value of attributes and ReturnAction allows for response definition including the Representation and all metadata. To achieve behavioral modelling, we transform our API methods into SOFL processes. We take advantage of the expressive nature of SOFL processes to define our modeled API behaviors. We achieve the interweaving of functional and security requirements by injecting boolean formulas in post condition of SOFL processes. To verify whether the interweaved functional and security requirements implement all expected functions correctly and satisfy the desired security constraints, we can optionally perform specification testing. Since implicit specifications do not indicate algorithms for implementation but are rather expressed with predicate expressions involving pre and post conditions for any given specification, we can substitute all the variables involved a process with concrete values of their types with results and evaluate their results in the form of truth values true or false. When conducting specification testing, we apply SOFL process animation technique to obtain the set of concrete values of output variables for each process functional scenario. We analyse test results by comparing the evaluation results with an analysis criteria. An analysis criteria is a predicate expression representing the properties to be verified. If the evaluation results are consistent with the predicate expression, the analysis show consistency between the process specification and its associated requirement. We generate the test cases for both input and output variables based on the user requirements. The test cases generated are usually based on test targets which are predicate expressions, such as the pre and post conditions of a process. when testing for conformance of a process specification to its associated service operation, we only need to observe the execution results of the process by providing concrete input values to all of its functional scenarios and analyze their defining conditions relative to user requirements. We present an empirical case study for validating the practicality and usability of our model driven formal engineering approach by applying it in developing a Salon Booking System. A total of 32 services covering functionalities provided by the Salon Booking System API were developed. We defined process specifications for the API services with their respective security requirements. The security requirements were injected in the threat modeling and behavioral modeling phase of our approach. We test for the interweaving of functional and security requirements in the specifications generated by our approach by conducting tests relative to original RAML specifications. Failed tests were exhibited in cases where injected security measure like requirement of an object level access control is not respected i.e., object level access control is not checked. Our generated SOFL specification correctly rejects such case by returning an appropriate error message while the original RAML specification incorrectly dictates to accept such request, because it is not aware of such measure. We further demonstrate a technique for generating SOFL specifications from a domain model via model to text transformation. The model to text transformation technique semi-automates the generation of SOFL formal specification in step 6 of our proposed approach. The technique allows for isolation of dynamic and static sections of the generated specifications. This enables our technique to have the capability of preserving the static sections of the target specifications while updating the dynamic sections in response to the changes of the underlying domain model representing the RESTful API in design. Specifically, our contribution is provision of a systemic model driven formal engineering approach for design and development of secure RESTful web APIs. The proposed approach offers a six-step methodology covering both structural and behavioral modelling of APIs with a focus on security. The most distinguished merit of the model to text transformation is the utilization of the API’s domain model as well as a metamodel that the domain model corresponds to as the foundation for generation of formal SOFL specifications that is a representation of API’s functional and security requirements.

To evaluate the fracture resistance of computer-aided design and computer-assisted manufacturing restorations as the abutment of removable partial dentures, experimental blocks, with the rest seat made of feldspar, hybrid resin composite, lithium disilicate glass ceramic, or zirconia, were subjected to loading by a metallic occlusal rest. The rest contacted the rest seat with an accurate fit and two mismatch contact conditions: bottom and sidewall contact. Zirconia exhibited the highest fracture load, and the fracture load of the accurate fit was significantly higher than that of the sidewall contact (p0.05) and insignificantly higher than that of the bottom contact (p0.05). A finite element analysis of the sidewall contact revealed a higher tensile stress concentration at the bottom of the rest seat than the other contact conditions. The mismatch between the rest and the restoration reduced fracture resistance, while zirconia as the abutment withstood the average occlusal force of the posterior region.

Background: In REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure), implantation of an atrial shunt device did not provide overall clinical benefit for patients with heart failure with preserved or mildly reduced ejection fraction. However, prespecified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial volume, and sex. Shunt implantation reduces left atrial pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). On the basis of these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. Methods: REDUCE LAP-HF II enrolled 626 patients with heart failure, ejection fraction ≥40%, exercise pulmonary capillary wedge pressure ≥25 mm Hg, and resting pulmonary vascular resistance Results: Compared with patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated left atrial pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio, 0.60 [95% CI, 0.42, 0.86]; P =0.005) and signal of clinical benefit in patients without PVD (win ratio, 1.31 [95% CI, 1.02, 1.68]; P =0.038). Patients with larger right atrial volumes and men had worse outcomes with the device and both groups were more likely to have pacemakers, heart failure with mildly reduced ejection fraction, and increased left atrial volume. For patients without latent PVD or pacemaker (n=313; 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio, 1.51 [95% CI, 1.14, 2.00]; P =0.004). Conclusions: In patients with heart failure with preserved or mildly reduced ejection fraction, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

Although the mean age of onset of social anxiety disorder (SAD) is during adolescence, we know relatively little about the neurodevelopmental correlates of subsyndromal social anxiety in early adolescence before SAD manifests. Here we examined frontal EEG alpha/delta ratio (a putative proxy of brain maturation) in relation social anxiety symptoms across early adolescence. Resting regional EEG spectral power measures were collected continuously for 4 min (2 min eyes-open, 2 min eyes-closed) in slow (i.e., delta) and fast (i.e., alpha) frequencies at Time 1, and self-reported social anxiety measures were collected concurrently at Time 1 and then prospectively approximately one year later (Time 2) in 103 typically developing 12- to 14-year-olds (46.6% female, M

Latissimus dorsi (LD) and teres major (TM) tears have become increasingly recognized injuries in professional baseball pitchers. The purpose of this study was to determine whether workload, as measured by the number of days of rest between outings, number of innings pitched, number of batters faced, and being a starting pitcher, is associated with an increased risk of sustaining an LD-TM tear in professional baseball pitchers.All professional baseball pitchers who sustained an LD-TM tear between 2011 and 2017 were identified using the Major League Baseball Health and Injury Tracking System. A separate player-usage data set was used to determine workload. We then compared workload variables between pitcher-games 2, 6, 12, and12 weeks prior to a documented LD-TM tear and pitcher-games from a non-LD-TM tear control group. In a paired analysis, we compared the acute workload (2, 6, and 12 weeks) prior to injury and the injured pitchers' non-acute workload12 weeks prior to injury.A total of 224 unique LD-TM tears were documented in the Major League Baseball Health and Injury Tracking System database. In most periods, player-games with more innings pitched and more batters faced were associated with a higher incidence of subsequent LD-TM tears. The number of days of rest was not a significant predictor of an LD-TM tear in the acute workload setting, but pitchers who sustained an LD-TM injury averaged fewer days of rest over the previous ≥12 weeks than controls (P.001). Pitchers who faced30 batters per game showed a 1.57-fold increase in the percentage of pitchers with a subsequent LD-TM tear as compared with pitchers who faced ≤5 batters per game. Significantly more starting pitchers were in the case group that sustained LD-TM tears over multiple time points than in the control group.Having a greater pitcher workload and being a starting pitcher were associated with an increased risk of sustaining LD-TM tears in professional baseball players. The average number of days of rest was only a risk factor for LD-TM tears over a 3-month or longer period.

There is controversial evidence regarding the effect of acute resistance exercise (ARE) on heart rate variability (HRV) parameters, which indicates the activities of the cardiac autonomic nervous system. The aim of this study was to perform a systematic review and meta-analysis of the literature on the effect of ARE on HRV parameters and identify its possible moderating factors.The PubMed-Medline, Web of Science, SPORTDiscus, and Cochrane Library databases were searched. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration was followed, and the methodological quality of the studies was evaluated. The level of significance was set at p ≤ 0.05. Twenty-six studies met the inclusion criteria. Main effect analyses between pre- and post-test interventions demonstrated an increase in normalized units low frequency (p0.001; standardized mean difference (SMD) = 0.78; 95% confidence interval (95%CI): 0.46‒1.11) and low frequency/high frequency ratio (p0.001; SMD = 0.82; 95%CI: 0.64‒0.99) and a decrease in standard deviation of the normal-to-normal (NN) interval (p0.001; SMD = -0.58; 95%CI: -0.85 to -0.30), root mean square of the successive differences (p0.001; SMD = -1.01; 95%CI: -1.29 to -0.74), and normalized units high frequency (p0.001; SMD: -1.08; 95%CI: -1.43 to -0.73) following ARE in healthy individuals range: 15 ± 1 to 48 ± 2 years; mean ± SD).There were differences between the subgroups in the number of sets used in an exercise (p = 0.05) for root mean square of the successive differences, as well as for exercise intensity (p = 0.01) and rest between sets (p = 0.05) for normalized units high frequency. Interestingly, there were differences between the subgroups in training volume for root mean square of the successive differences (p = 0.01), normalized units high frequency (p = 0.003) and normalized units low frequency (p = 0.02).Overall, there was a withdrawal of cardiac parasympathetic and activation of cardiac sympathetic modulations following ARE, and these changes were greater with higher training volume ∼30 min after ARE in healthy individuals. Furthermore, the number of sets, intensity, and rest between sets affected HRV parameters. However, gender, body mass index, and training status did not influence the changes in HRV parameters as a response to ARE.

Prolonged repolarization duration is a significant total mortality (TM) predictor in post-myocardial infarction patients.We examined the clinical significance of QT interval that was extracted from a Short Resting Holter ECG (SRH ECG - 30-min duration) as a TM predictor in heart failure (HF) patients.One hundred forty-five HF patients (male = 84%, mean age = 64 ± 12 years, mean LVEF = 33 ± 10%) underwent an SRH ECG recording for 30 min. These high-resolution ECG signals were analyzed and the QT interval was calculated and corrected according to the Fridericia formula. After 42.1 months, 26 patients died.Univariate analysis for Deceased and Living groups: QTc:455 ± 33 ms vs 441 ± 32 ms (p = 0.04), LVEF:32 ± 10% vs 34 ± 9% (p0.5), Mean Heart Rate: 73 ± 11 bpm vs 69 ± 12 bpm (p = 0.2), SDNN/HRV: 45 ± 42 ms vs 41 ± 29 ms (p = 0.4), QRS: 123 ± 26 ms vs 119 ± 29 ms (p = 0.5). Multivariate Cox regression analysis with model adjusted for QTc, Mean Heart Rate, LVEF, QRS, revealed that QTc-Fridericia interval was an independent TM predictor (H.R.:1.017, 95% C.I.: 1.003-1.030, p = 0.01). The cut-off point of 490 ms (90th percentile) in the same model presented HR: 2.9 for TM (95%C.I.: 1.066-7.882, p = 0.03). Kaplan Meier curves depicted a clear difference in survival between the two patients' groups (QTc Group≥490 ms vs QTc Group490 ms). The curve diverge was important (log-rank, p = 0.02).A fast risk stratification approach with SRH ECG recording is an efficient method for flash evaluation of mortality risk in HF patients.

Previous neuroimaging studies have demonstrated that sleep is associated with brain functional changes in some specific brain regions. However, few studies have examined the relationship between all possible functional connectivities (FCs) within the sensory/somatomotor network (SSN) and the sleep quality of young male samples. The SSN consists of two motor cortices and is known to play a critical role in sleep. Poor sleep quality may be associated with increased sensory/somatomotor functional connectivity during rest. Hence, 202 young male participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and completed the Pittsburgh Sleep Quality Index (PSQI). Results indicated that increased functional connectivity within the SSN was associated with poor sleep quality. Specifically, the total PSQI score was positively correlated with the increased functional connectivity of the left paracentral lobule (PCL), bilateral precentral gyrus (PreCG), supplementary motor area (SMA) and bilateral postcentral gyrus (PoCG). Additionally, our findings also exhibited that (a) the subjective sleep quality factor of PSQI was positively correlated with FC between the bilateral PoCG and the bilateral PCL as well as between the left PreCG and the right SMA; (b) the sleep latency factor of PSQI was positively correlated with FC between the left PoCG and the right precuneus (PCUN); (c) the sleep disturbances factor of PSQI was positively correlated with FC between the left PCL and the right PoCG, and (d) the daytime dysfunction factor of PSQI was positively correlated with FC between the bilateral PoCG and the left PCL as well as between the bilateral PreCG and the SMA. In short, our findings can be comprehensively understood as neural mechanisms of intrinsic SSN connectivity are associated with sleep quality of man. Meanwhile, it may expand our knowledge and provide new insight into a deeper understanding of the neurobiological mechanisms of sleep or sleep problems.

This study evaluates whether the Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C) improves objective sleep and rest-activity rhythms in a sample of youth with an evening circadian preference (ECP).Youth with an ECP aged 10-18 years were randomized to receive 6 sessions of TranS-C (n = 60) or Psychoeducation (PE; n = 58). For one week prior to beginning treatment and within 2 weeks of completing treatment, participants wore an actiwatch to assess objective sleep and rest-activity rhythms.Among TranS-C participants, there were significant pre-post improvements in weeknight total sleep time (TST), weekend TST, and weeknight-weekend discrepancy in TST and sleep offset time. These changes were not significant in PE. There was no significant treatment by time interactions for the sleep or rest-activity outcomes.For youth with an ECP, TranS-C improves select objective sleep but not rest-activity outcomes, though compared to PE, these benefits did not reach statistical significance.

This study investigated age-related changes in the EEG of subtypes of Attention-Deficit/Hyperactivity Disorder (AD/HD) compared with neurotypical controls, using an eyes-open resting condition. Two hundred and twenty five children between the ages of 5 and 16 years participated in this study. Groups consisted of AD/HD of the combined (AD/HDcom) and inattentive (AD/HDin) types, which were compared with controls for each of three age ranges: Young (5-8 years), Middle (9-12 years), and Old (13-16 years). The EEG was recorded and analyzed using AMLAB hardware and software, and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands. Compared to controls, the AD/HD groups had globally increased relative theta. Regional differences were found for absolute and relative alpha and beta. Compared to AD/HDcom, AD/HDin had globally reduced total power, absolute and relative theta, and absolute alpha. Regional differences only were found for absolute and relative delta, absolute beta, and relative alpha. No simple interactions were found for diagnostic factors with age. These results indicate that maturational effects can be observed between subtypes of AD/HD and controls in the eyes-open condition with similarities to those reported in eyes-closed conditions, although substantial differences are apparent in the maturation of fast wave activity, primarily alpha. These results provide evidence of maturational differences between subtypes of AD/HD in eyes-open conditions, and provide additional support for the suggestion that subtypes of AD/HD differ in severity rather than the nature of underlying neurological impairment.

BACKGROUND/INTRODUCTION: Autism spectrum disorder (ASD) is characterized by atypical functional connectivity (FC) within and between distributed brain networks. However, FC findings have often been inconsistent, possibly due to a focus on static FC rather than brain dynamics. Lagged connectivity analyses aim at evaluating temporal latency, and presumably neural propagation, between regions. This approach may, therefore, reveal a more detailed picture of network organization in ASD than traditional FC methods. METHODS: The current study evaluated whole-brain lag patterns in adolescents with ASD (n = 28) and their typically developing peers (n = 22). Functional magnetic resonance imaging data were collected during rest and during a lexico-semantic decision task. Optimal lag was calculated for each pair of regions of interest by using cross-covariance, and mean latency projections were calculated for each region. RESULTS: Latency projections did not regionally differ between groups, with the same regions emerging among the “earliest” and “latest.” Although many of the longest absolute latencies were preserved across resting-state and task conditions, lag patterns overall were affected by condition, as many regions shifted toward zero-lag during task performance. Lag structure was also strongly associated with literature-derived estimates of arterial transit time. DISCUSSION: Results suggest that lag patterns are broadly typical in ASD but undergo changes during task performance. Moreover, lag patterns appear to reflect a combination of neural and vascular sources, which should be carefully considered when interpreting lagged FC. IMPACT STATEMENT: Altered brain dynamics have been proposed in autism spectrum disorder (ASD). Lagged functional connectivity analysis uses cross-correlation between functional magnetic resonance imaging (fMRI) time series to determine regional latency. Few studies have examined blood oxygen level-dependent (BOLD) lag in ASD, and findings have been inconsistent. Using multi-echo fMRI data with improved artifact detection and removal, we find differences in lag structure between task and rest states, but not between adolescents with ASD and typically developing peers. Additional analyses exploring links with arterial transit time, however, highlight the impact of vascular organization on BOLD lag patterns and its potential to confound measures of neural dynamics.

A handling procedure of off-wrist episodes in actimetry time series of motor activity is presented using two records (regular vs. irregular sleep-wake cycle and daytime activity) of 14 consecutive days sampled in 1-minute epochs. We generated single missing value (NA) intervals of 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h as well as random NA episodes following probabilistic rules to simulate real-life off-wrist episodes. Then, we replaced these episodes with “zeroes” (i.e., the default of immobility records), mean or median of the remaining 13 days corresponding to the missing bins. Single missing episodes of up to 12 h resulted in less than 5% variation from the original values. The irregular series showed higher variability in acrophase, MESOR, L5, M10 and RA compared to the regular series. Random missing allocation simulating real-life off-wrist episodes resulted in significant changes in most parameters, and the imputation of zeroes significantly increased the variance; however, replacing NA with mean or median resulted in patterns similar to those of NA. We recommend replacing ‘zeroes’ with NA whenever possible, given the risk of inflating invariance using zeroes. If the parameters cannot be computed in the presence of NA, we recommend using the weekly mean of corresponding timepoints.

Resting-state functional connectivity (rs-FC) is widely used to examine the functional architecture of the brain, and the blood-oxygenation-level-dependent (BOLD) signal is often utilized for determining rs-FC. However, the BOLD signal is susceptible to various factors that have less influence on the cerebral blood flow (CBF). Therefore, CBF could comprise an alternative for determining rs-FC. Since acquisition duration is one of the essential parameters for obtaining reliable rs-FC, we investigated the effect of acquisition duration on CBF-based rs-FC to examine the reliability of CBF-based rs-FC. Nineteen participants underwent CBF scanning for a total duration of 50 min. Variance of CBF-based rs-FC within the whole brain and 13 large-scale brain networks at various acquisition durations was compared to that with a 50-min duration using the Levene's test. Variance of CBF-based rs-FC at any durations did not differ from that at a 50-min duration (p .05). Regarding variance of rs-FC within each large-scale brain network, the acquisition duration required to obtain reliable estimates of CBF-based rs-FC was shorter than 10 min and varied across large-scale brain networks. Altogether, an acquisition duration of at least 10 min is required to obtain reliable CBF-based rs-FC. These results indicate that CBF-based resting-state functional magnetic resonance imaging (rs-fMRI) with more than 10 min of total acquisition duration could be an alternative method to BOLD-based rs-fMRI to obtain reliable rs-FC.

The goal of this study was to determine whether the degree of weight loss after 6 months of a behavior-based intervention is related to baseline connectivity within two functional networks (FNs) of interest, FN1 and FN2, in a group of older adults with obesity.Baseline functional magnetic resonance imaging data were collected following an overnight fast in 71 older adults with obesity involved in a weight-loss intervention. Functional brain networks in a resting state and during a food-cue task were analyzed using a mixed-regression framework to examine the relationships between baseline networks and 6-month change in weight.During the resting condition, the relationship of baseline brain functional connectivity and network clustering in FN1, which includes the visual cortex and sensorimotor areas, was significantly associated with 6-month weight loss. During the food-cue condition, 6-month weight loss was significantly associated with the relationship between baseline brain connectivity and network global efficiency in FN2, which includes executive control, attention, and limbic regions.These findings provide further insight into complex functional circuits in the brain related to successful weight loss and may ultimately aid in developing tailored behavior-based treatment regimens that target specific brain circuitry.

Real-time quality assessment (rtQA) of functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) signal changes is critical for neuroimaging research and clinical applications. The losses of BOLD sensitivity because of different types of technical and physiological noise remain major sources of fMRI artifacts. Due to difficulty of subjective visual perception of image distortions during data acquisitions, a comprehensive automatic rtQA is needed. To facilitate rapid rtQA of fMRI data, we applied real-time and recursive quality assessment methods to whole-brain fMRI volumes, as well as time-series of target brain areas and resting-state networks. We estimated recursive temporal signal-to-noise ratio (rtSNR) and contrast-to-noise ratio (rtCNR), and real-time head motion parameters by a framewise rigid-body transformation (translations and rotations) using the conventional current to template volume registration. In addition, we derived real-time framewise (FD) and micro (MD) displacements based on head motion parameters and evaluated the temporal derivative of root mean squared variance over voxels (DVARS). For monitoring time-series of target regions and networks, we estimated the number of spikes and amount of filtered noise by means of a modified Kalman filter. Finally, we applied the incremental general linear modeling (GLM) to evaluate real-time contributions of nuisance regressors (linear trend and head motion). Proposed rtQA was demonstrated in real-time fMRI neurofeedback runs without and with excessive head motion and real-time simulations of neurofeedback and resting-state fMRI data. The rtQA was implemented as an extension of the open-source OpenNFT software written in Python, MATLAB and C++ for neurofeedback, task-based, and resting-state paradigms. We also developed a general Python library to unify real-time fMRI data processing and neurofeedback applications. Flexible estimation and visualization of rtQA facilitates efficient rtQA of fMRI data and helps the robustness of fMRI acquisitions by means of substantiating decisions about the necessity of the interruption and re-start of the experiment and increasing the confidence in neural estimates.

Background Depression is one typical mood disorder in Parkinson’s disease (DPD). The alterations in the resting-state brain activities are believed to be associated with DPD. These resting-state activities are regulated by neurophysiological components over multiple temporal scales. The multiscale dynamics of these spontaneous fluctuations are thus complex, but not well-characterized. Objective To characterize the complexity of the spontaneous blood-oxygen-level-dependent (BOLD) of fMRI in DPD. We hypothesized that (1) compared to non-depression PD (NDPD), the complexity in DPD would be lower; and (2) the diminished complexity would be associated with lower connections/communications between brain regions. Methods Twenty-nine participants (10 in DPD and 19 in NDPD) who were naïve to medications completed a resting-sate functional MRI scan. The BOLD complexity within each voxel was calculated by using multiscale entropy (MSE). The complexity of the whole brain and each of the 90 regions parcellated following automated-anatomical-labeling template was then obtained by averaging voxel-wised complexity across all brain regions or within each region. The level of connections of regions with diminished complexity was measured by their own global functional connectivity (FC). Results As compared to NDPD patients, the whole-brain complexity and complexity in 18 regions were significantly lower in DPD (F > 16.3, p p = 0.000 ~ 0.030). Conclusion The results from this pilot study suggest that the resting-state BOLD complexity may provide critical knowledge into the pathology of DPD. Future studies are thus warranted to confirm the findings of this study.

BACKGROUND: Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for non-invasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind placebo controlled clinical trial. METHODS: In this current study, we aimed to replicate successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. 84 participants were randomized to receive verum or sham IAF-tACS. Electrical brain activity was recorded during rest and while viewing emotionally-salient images before and after stimulation to investigate if the modulation of alpha oscillation by tACS exhibited specificity with regards to valence. RESULTS: In agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared to placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants. CONCLUSION: Together these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD. NATIONAL CLINICAL TRIAL: NCT03449979, “Single Session of tACS in a Depressive Episode (SSDE)” https://www.clinicaltrials.gov/ct2/show/NCT03449979

Previous test-retest analysis of EEG mostly focused on eyes open and eyes closed resting-state. However, less attention was paid to the EEG during the subject-driven mental imaginary task state. In the current study, we compared the test-retest reproducibility of EEG spectrum in three mental imaginary task states (i.e. performed mental arithmetic, recalled the events of their day, and silently sang lyrics) and two resting states (i.e. eyes open and closed) during three EEG sessions. The resting state with eyes closed has the highest reproducibility, while the resting state with eyes opened has the lowest reproducibility for the spectral features of EEG signals at the sensor level. However, the reproducibility during eyes-open ranked higher among the five states at the source level. Moreover, the mental arithmetic state has the highest reproducibility among all the three task states. And its reproducibility in certain rhythms (theta, gamma, etc) was higher than the resting states. The reproducibility of the EEG spectrum was also investigated from the perspective of large-scale brain networks. The dorsal attention network showed the highest reproducibility in a wide frequency range of the alpha and beta rhythms. Our study suggests the importance of task selection based on the target brain region and the target frequency band. This may provide some suggestions for future researchers to choose appropriate experimental paradigms and provide a guideline on EEG study for the basic and clinical applications.