Outcome of severe COVID-19: spotlight on fatigue, fatigability, multidomain complaints and pattern of cognitive deficits in a case series without prior brain dysfunction and without COVID-19-related stroke and/or cardiac arrest.

BACKGROUND: Population-wide surveys and large-scale investigations highlighted the presence of cognitive deficits in the acute and postacute stages of severe COVID-19; a few studies documented their occurrence in cases without prior or COVID-19-related brain damage. The evolution of cognitive deficits in the latter population and their relationship to the post-COVID-19 fatigue syndrome are poorly understood. CASE PRESENTATION: We report the outcome at 12 months after severe COVID-19 involving an intensive care unit stay and mechanical ventilation in six (five Caucasian and one Asian) patients (age range: 53-71 years, mean age 61.7 ± 6.5 years) without history of prior brain dysfunction and without stroke and/or cardiac arrest during or after COVID-19. All patients reported pervading mental and physical fatigue as well as numerous multidomain complaints, which impacted everyday life. Individual patients described mental fatigability, apathy, and/or anxiety. Standardized neuropsychological tests revealed isolated symptoms of cognitive dysfunction or performance at the lower limit of the norm in the attentional, executive, and/or working memory domains in four of the six patients. Somatic scales documented dyspnoea, muscle weakness, olfactory disorder, and/or minor sleep problems in some, but not all, patients. CONCLUSION: Fatigue, fatigability, multidomain complaints, cognitive difficulties, or dysfunction, as well as isolated neurobehavioral and/or psychiatric and/or somatic symptoms, tend to occur in the aftermath of severe COVID-19 and persist at 12 months, even in the absence of prior and/or COVID-19-related brain damage. This clinical situation, which impacts everyday life, calls for a detailed investigation of patients' complaints, its neural underpinning, and an elaboration of specific rehabilitation programs.

The provision and impact of rehabilitation provided by physiotherapists in children and young people with congenital heart disease following cardiac surgery: a scoping review.

INTRODUCTION: Children with congenital heart disease (CHD) are at risk of delayed motor development with increased risk for those requiring cardiac surgical intervention. We conducted a scoping review to identify the provision and impact of physiotherapy-delivered rehabilitation in children and young people with CHD following cardiac surgery. METHODS: CINAHL, EMBASE, PUBMED, AHMED, EMCARE, Cochrane Database of Systematic Reviews, NHS Evidence databases were searched (2000-2022). Included studies were published in full, in English and reported the use of physiotherapy in CHD (participants 0-18years) post-surgical procedure. Articles were screened by title and abstract and through full-text review with results structured in accordance with the PAGER framework and PRISMA- ScR checklist. RESULTS: Seven full text peer reviewed papers published 2014-2021 were identified from 5747 papers screened. Included papers were predominantly non-randomised cohort studies with a sample size of between one and 247. Study participants ranged from eight days to 16 years, with a variety of congenital heart defects and surgical procedures. The provision of physiotherapy varied with a range of rehabilitation formats and physiotherapeutic interventions utilised. Physiotherapy provision appeared to have a positive impact on functional/ developmental outcomes and muscle strength. DISCUSSION: Assessing the impact and provision of physiotherapy in CHD post-surgical intervention is challenging based on the published literature, due to small sample sizes, lack of control groups, heterogeneous demographics and variable intervention and formats delivered. Further research is required to identify the optimum format of physiotherapy provision and establish the potential impact of physiotherapy delivered rehabilitation on motor function and development. CONTRIBUTION OF THE PAPER.

Paved with good intentions: How our systems intersect to create health disparities for multiply marginalized youth.

BACKGROUND: Youth who hold multiply marginalized identities often experience barriers in accessing care following psychiatric hospitalization METHODOLOGY: The following commentary piece shares a case amalgamation from a multidisciplinary gender clinic in a tertiary care children's hospital which illustrates the myriad of ways that our current mental healthcare systems fail to connect youth efficiently and effectively to the evidence-based, culturally relevant, and affirming care that they require, particularly youth experiencing overlapping systems of discrimination and disadvantage. CONCLUSIONS: This piece highlights the inaccessibility of dialectical behavior therapy for multiply marginalized youth, and outlines suggestions for improving access to high-quality care for minoritized youth engaging in suicidal behavior.

Emotional sounds in space: asymmetrical representation within early-stage auditory areas.

Evidence from behavioral studies suggests that the spatial origin of sounds may influence the perception of emotional valence. Using 7T fMRI we have investigated the impact of the categories of sound (vocalizations; non-vocalizations), emotional valence (positive, neutral, negative) and spatial origin (left, center, right) on the encoding in early-stage auditory areas and in the voice area. The combination of these different characteristics resulted in a total of 18 conditions (2 categories x 3 valences x 3 lateralizations), which were presented in a pseudo-randomized order in blocks of 11 different sounds (of the same condition) in 12 distinct runs of 6 min. In addition, two localizers, i.e., tonotopy mapping; human vocalizations, were used to define regions of interest. A three-way repeated measure ANOVA on the BOLD responses revealed bilateral significant effects and interactions in the primary auditory cortex, the lateral early-stage auditory areas, and the voice area. Positive vocalizations presented on the left side yielded greater activity in the ipsilateral and contralateral primary auditory cortex than did neutral or negative vocalizations or any other stimuli at any of the three positions. Right, but not left area L3 responded more strongly to (i) positive vocalizations presented ipsi- or contralaterally than to neutral or negative vocalizations presented at the same positions; and (ii) to neutral than positive or negative non-vocalizations presented contralaterally. Furthermore, comparison with a previous study indicates that spatial cues may render emotional valence more salient within the early-stage auditory areas.

Does hand modulate the reshaping of the attentional system during rightward prism adaptation? An fMRI study.

Adaptation to right-deviating prisms (R-PA), that is, learning to point with the right hand to targets perceived through prisms, has been shown to change spatial topography within the inferior parietal lobule (IPL) by increasing responses to left, central, and right targets on the left hemisphere and decreasing responses to right and central targets on the right hemisphere. As pointed out previously, this corresponds to a switch of the dominance of the ventral attentional network from the right to the left hemisphere. Since the encoding of hand movements in pointing paradigms is side-dependent, the choice of right vs. left hand for pointing during R-PA may influence the visuomotor adaptation process and hence the reshaping of the attentional system. We have tested this hypothesis in normal subjects by comparing activation patterns to visual targets in left, central, and right fields elicited before and after adaptation to rightward-deviating prisms using the right hand (RWRH) with those in two control groups. The first control group underwent adaptation to rightward-deviating prisms using the left hand, whereas the second control group underwent adaptation to leftward-deviating prisms using the right hand. The present study confirmed the previously described enhancement of left and central visual field representation within left IPL following R-PA. It further showed that the use of right vs. left hand during adaptation modulates this enhancement in some but not all parts of the left IPL. Interestingly, in some clusters identified in this study, L-PA with right hand mimics partially the effect of R-PA by enhancing activation elicited by left stimuli in the left IPL and by decreasing activation elicited by right stimuli in the right IPL. Thus, the use of right vs. left hand modulates the R-PA-induced reshaping of the ventral attentional system. Whether the choice of hand during R-PA affects also the reshaping of the dorsal attentional system remains to be determined as well as possible clinical applications of this approach. Depending on the patients' conditions, using the right or the left hand during PA might potentiate the beneficial effects of this intervention.

Choosing Sides: Impact of Prismatic Adaptation on the Lateralization of the Attentional System.

Seminal studies revealed differences between the effect of adaptation to left- vs. right-deviating prisms (L-PA, R-PA) in normal subjects. Whereas L-PA leads to neglect-like shift in attention, demonstrated in numerous visuo-spatial and cognitive tasks, R-PA has only minor effects in specific aspects of a few tasks. The paucity of R-PA effects in normal subjects contrasts with the striking alleviation of neglect symptoms in patients with right hemispheric lesions. Current evidence from activation studies in normal subjects highlights the contribution of regions involved in visuo-motor control during prism exposure and a reorganization of spatial representations within the ventral attentional network (VAN) after the adaptation. The latter depends on the orientation of prisms used. R-PA leads to enhancement of the ipsilateral visual and auditory space within the left inferior parietal lobule (IPL), switching thus the dominance of VAN from the right to the left hemisphere. L-PA leads to enhancement of the ipsilateral space in right IPL, emphasizing thus the right hemispheric dominance of VAN. Similar reshaping has been demonstrated in patients. We propose here a model, which offers a parsimonious explanation of the effect of L-PA and R-PA both in normal subjects and in patients with hemispheric lesions. The model posits that prismatic adaptation induces instability in the synaptic organization of the visuo-motor system, which spreads to the VAN. The effect is lateralized, depending on the side of prism deviation. Successful pointing with prisms implies reaching into the space contralateral, and not ipsilateral, to the direction of prism deviation. Thus, in the hemisphere contralateral to prism deviation, reach-related neural activity decreases, leading to instability of the synaptic organization, which induces a reshuffling of spatial representations in IPL. Although reshuffled spatial representations in IPL may be functionally relevant, they are most likely less efficient than regular representations and may thus cause partial dysfunction. The former explains, e.g., the alleviation of neglect symptoms after R-PA in patients with right hemispheric lesions, the latter the occurrence of neglect-like symptoms in normal subjects after L-PA. Thus, opting for R- vs. L-PA means choosing the side of major IPL reshuffling, which leads to its partial dysfunction in normal subjects and to recruitment of alternative or enhanced spatial representations in patients with hemispheric lesions.

The provision of person-centred care for care home residents with stroke: An ethnographic study.

Care home residents with stroke have higher levels of disability and poorer access to health services than those living in their own homes. We undertook observations and semi-structured interviews (n = 28 participants) with managers, staff, residents who had experienced a stroke and their relatives in four homes in London, England, in 2018/2019. Thematic analysis revealed that residents' needs regarding valued activity and stroke-specific care and rehabilitation were not always being met. This resulted from an interplay of factors: staff's lack of recognition of stroke and its effects; gaps in skills; time pressures; and the prioritisation of residents' safety. To improve residential care provision and residents' quality of life, care commissioners, regulators and providers may need to re-examine how care homes balance safety and limits on staff time against residents' valued activity, alongside improving access to specialist healthcare treatment and support.

The prevalence and assessment of pain and dyspnoea in acute exacerbations of COPD: A systematic review.

BACKGROUND: Dyspnoea and pain are symptoms of chronic obstructive pulmonary disease (COPD). This review focused upon pain and dyspnoea during hospital admissions for acute exacerbations of COPD (AECOPD), with the aim of examining prevalence, assessment, clinical associations, and researcher-reported implications of these symptoms. METHODS: Four electronic databases were searched from inception to 31 May 2021. Full text versions of studies were assessed for methodological quality and data were extracted independently by two reviewers. Where data permitted, pooled prevalence of pain and dyspnoea were calculated by meta-analysis. RESULTS: Four studies were included. The pooled prevalence of pain and dyspnoea was 44% (95% confidence interval (CI) 35%-52%) and 91% (95% CI 87%-94%) respectively. An array of instruments with varying focal periods were reported (pain: six tools, dyspnoea: four tools). Associations and clinical implications between the two symptoms at the time of hospital admission were rarely reported. CONCLUSIONS: Few studies reported prevalence of pain and dyspnoea during an AECOPD. A greater understanding into the prevalence, intensity and associations of these symptoms during AECOPD could be furthered by use of standardised assessment tools with clearly defined focal periods.

Contribution of Hydrolysis and Drying Conditions to Whey Protein Hydrolysate Characteristics and In Vitro Antioxidative Properties.

During the generation of functional food ingredients by enzymatic hydrolysis, parameters such as choice of enzyme, reaction pH and the drying process employed may contribute to the physicochemical and bio-functional properties of the resultant protein hydrolysate ingredients. This study characterised the properties of spray- (SD) and freeze-dried (FD) whey protein hydrolysates (WPHs) generated using Alcalase® and Prolyve® under pH-stat and free-fall pH conditions. The enzyme preparation used affected the physicochemical and antioxidative properties but had no impact on powder composition, morphology or colour. SD resulted in spherical particles with higher moisture content (~6%) compared to the FD powders (~1%), which had a glass shard-like structure. The SD-WPHs exhibited higher antioxidative properties compared to the FD-WPHs, which may be linked to a higher proportion of peptides <1 kDa in the SD-WPHs. Furthermore, the SD- and FD-WPHs had similar peptide profiles, and no evidence of Maillard reaction product formation during the SD processing was evident. The most potent in vitro antioxidative WPH was generated using Alcalase® under free-fall pH conditions, followed by SD, which had oxygen radical absorbance capacity and Trolox equivalent (TE) antioxidant capacity values of 1132 and 686 µmol TE/g, respectively. These results demonstrate that both the hydrolysis and the drying process impact the biofunctional (antioxidant) activity of WPHs.

The Hearts in Rhythm Organization: A Canadian National Cardiogenetics Network.

BACKGROUND: The Hearts in Rhythm Organization (HiRO) is a team of Canadian inherited heart rhythm and cardiomyopathy experts, genetic counsellors, nurses, researchers, patients, and families dedicated to the detection of inherited arrhythmias and cardiomyopathies, provision of best therapies, and protection from the tragedy of sudden cardiac arrest. METHODS: Recently, existing disease-specific registries were merged into the expanded National HiRO Registry, creating a single common data set for patients and families with inherited conditions that put them at risk for sudden death in Canada. Eligible patients are invited to participate in the registry and optional biobank from 20 specialized cardiogenetics clinics across Canada. RESULTS: Currently, there are 4700 participants enrolled in the National HiRO Registry, with an average of 593 participants enrolled annually over the past 5 years. The capacity to enable knowledge translation of research findings is built into HiRO's organizational infrastructure, with 3 additional working groups (HiRO Clinical Care Committee, HiRO Active Communities Committee, and HiRO Annual Symposium Committee), supporting the organization's current goals and priorities as set alongside patient partners. CONCLUSION: The National HiRO Registry aims to be an integrated research platform to which researchers can pose novel research questions leading to a better understanding, detection, and clinical care of those living with inherited heart rhythm and cardiomyopathy conditions and ultimately to prevent sudden cardiac death.

CONTEXTE: La Hearts in Rhythm Organization (HiRO) est une équipe d'experts canadiens en matière de rythmes cardiaques et de cardiomyopathies héréditaires, de conseillers en génétique, d'infirmières, de chercheurs, de patients et de familles qui se consacrent à la détection des arythmies et des cardiomyopathies héréditaires, à la mise en place des meilleures thérapies et à la protection contre la tragédie que représente une mort subite d'origine cardiaque. MÉTHODES: Récemment, les registres existants relatifs à des maladies spécifiques ont été fusionnés en un registre national élargi de l'HiRO, créant ainsi un ensemble de données commun unique à destination des patients et leurs familles, atteints de maladies héréditaires, qui sont à risque de mort subite au Canada. Les patients admissibles sont invités à s'associer au registre et à la biobanque facultative regroupant 20 cliniques spécialisées en cardiogénétique au Canada. RÉSULTATS: Actuellement, 4 700 participants sont inscrits au registre national de l'HiRO, avec une moyenne de 593 participants inscrits chaque année au cours des cinq dernières années. La capacité à favoriser l'application des connaissances issues de la recherche fait partie de la structure organisationnelle de l'HiRO, avec trois groupes de travail supplémentaires (comité des soins cliniques de l'HiRO, comité des communautés cctives de l'HiRO et comité du symposium annuel de l'HiRO), soutenant les objectifs et les priorités actuels de l'organisation tels qu'ils ont été fixés en partenariat avec les patients. CONCLUSION: Le registre national de l'HiRO vise à devenir une plateforme de recherche intégrée au sein de laquelle les chercheurs peuvent exposer des questions de recherche inédites permettant de mieux comprendre, détecter et soigner les personnes atteintes de troubles du rythme cardiaque et de cardiomyopathie héréditaires et, à terme, de prévenir la mort subite d'origine cardiaque.

Why Rehabilitation must have priority during and after the COVID-19-pandemic: A position statement of the Global Rehabilitation Alliance.

COVID-19 has become a pandemic with strong influence on health systems. In many cases it leads to a disruption of rehabilitation service provision. On the other hand, rehabilitation must be an integral part of COVID-19 management. Rehabilitation for COVID-19 should start from acute and early post-acute care and needs to be continued in the post-acute and long-term rehabilitation phase. Of course, it should follow specific safety protocol. Additionally, rehabilitation must be kept available for all other people who are in need. From the perspective of health system, the Global Rehabilitation Alliance urges decision makers to ensure that rehabilitation services will be available for all patients with COVID-19 in the acute, post-acute and long-term phase. Additionally, it must be ensured that all other persons with rehabilitation need have access to rehabilitation services. Rehabilitation services must be equipped with personal protection equipment and follow strict hygiene measures. In particular, rehabilitation must be accessible for vulnerable populations. For that reason, rehabilitation must be kept a health priority during the COVID-19 pandemic and given adequate financial resources. Last but not least, scientific studies should be performed to clarify the impact of the pandemic on rehabilitation services as well as on the needs for rehabilitation of COVID-19 patients.

A brief exposure to rightward prismatic adaptation changes resting-state network characteristics of the ventral attentional system.

A brief session of rightward prismatic adaptation (R-PA) has been shown to alleviate neglect symptoms in patients with right hemispheric damage, very likely by switching hemispheric dominance of the ventral attentional network (VAN) from the right to the left and by changing task-related activity within the dorsal attentional network (DAN). We have investigated this very rapid change in functional organisation with a network approach by comparing resting-state connectivity before and after a brief exposure i) to R-PA (14 normal subjects; experimental condition) or ii) to plain glasses (12 normal subjects; control condition). A whole brain analysis (comprising 129 regions of interest) highlighted R-PA-induced changes within a bilateral, fronto-temporal network, which consisted of 13 nodes and 11 edges; all edges involved one of 4 frontal nodes, which were part of VAN. The analysis of network characteristics within VAN and DAN revealed a R-PA-induced decrease in connectivity strength between nodes and a decrease in local efficiency within VAN but not within DAN. These results indicate that the resting-state connectivity configuration of VAN is modulated by R-PA, possibly by decreasing its modularity.

Recent advances in understanding and managing self-harm in adolescents.

Adolescent suicide is a serious public health problem, and non-suicidal self-injury (NSSI) is both highly comorbid with suicidality among adolescents and a significant predictor of suicide attempts (SAs) in adolescents. We will clarify extant definitions related to suicidality and NSSI and the important similarities and differences between these constructs. We will also review several significant risk factors for suicidality, evidence-based and evidence-informed safety management strategies, and evidence-based treatment for adolescent self-harming behaviors. Currently, dialectical behavior therapy (DBT) for adolescents is the first and only treatment meeting the threshold of a well-established treatment for self-harming adolescents at high risk for suicide. Areas in need of future study include processes underlying the association between NSSI and SAs, clarification of warning signs and risk factors that are both sensitive and specific enough to accurately predict who is at imminent risk for suicide, and further efforts to sustain the effects of DBT post-treatment. DBT is a time- and labor-intensive treatment that requires extensive training for therapists and a significant time commitment for families (generally 6 months). It will therefore be helpful to assess whether other less-intensive treatment options can be established as evidence-based treatment for suicidal adolescents.

Processing pathways for emotional vocalizations.

Emotional sounds are processed within a large cortico-subcortical network, of which the auditory cortex, the voice area, and the amygdala are the core regions. Using 7T fMRI, we have compared the effect of emotional valence (positive, neutral, and negative) and the effect of the type of environmental sounds (human vocalizations and non-vocalizations) on neural activity within individual early stage auditory areas, the voice area, and the amygdala. A two-way ANOVA was applied to the BOLD time course within each ROI. In several early stage auditory areas, it yielded a significant main effect of vocalizations and of valence, but not a significant interaction. Significant interaction as well as significant main effects of vocalization and of valence were present in the voice area; the former was driven by a significant emotional modulation of vocalizations but not of other sounds. Within the amygdala, only the main effect of valence was significant. Post-hoc correlation analysis highlighted coupling between the voice area and early stage auditory areas during the presentation of any vocalizations, and between the voice area and the right amygdala during positive vocalizations. Thus, the voice area is selectively devoted to the encoding of the emotional valence of vocalizations; it shares with several early stage auditory areas encoding characteristics for vocalizations and with the amygdala for the emotional modulation of vocalizations. These results are indicative of a dual pathway, whereby the emotional modulation of vocalizations within the voice area integrates the input from the lateral early stage auditory areas and from the amygdala.

Prism adaptation enhances decoupling between the default mode network and the attentional networks.

Prism adaptation (PA) is a procedure used for studying visuomotor plasticity in healthy individuals, as well as for alleviating spatial neglect in patients. The adaptation is achieved by performing goal-directed movements while wearing prismatic lenses that induce a lateral displacement of visual information. This results in an initial movement error that is compensated by a recalibration of sensory-motor coordinates; consequently, a lateral bias in both motor and perceptual measurements occurs after prism removal, i.e., after effects. Neuroimaging studies have shown that a brief exposure to a rightward-shifting prism changes the activations in the inferior parietal lobule (IPL) and modulates interhemispheric balance during attention tasks. However, it is yet unknown how PA changes global interplay between cortical networks as evident from task-free resting state connectivity. Thus we compared resting state functional connectivity patterns before ('Pre') and after ('Post') participants performed a session of pointing movements with a rightward-shifting prism (N = 14) or with neutral lenses (as a control condition; N = 12). Global connectivity analysis revealed significant decreases in functional connectivity following PA in two nodes of the Default Mode Network (DMN), and in the left anterior insula. Further analyses of these regions showed specific connectivity decrease between either of the DMN nodes and areas within the attentional networks, including the inferior frontal gyrus, the anterior insula and the right superior temporal sulcus. On the other hand, the anterior insula decreased its connectivity to a large set of areas, all within the boundaries of the DMN. These results demonstrate that a brief exposure to PA enhances the decoupling between the DMN and the attention networks. The change in interplay between those pre-existing networks might be the basis of the rapid and wide-ranged behavioural changes induce by PA in healthy individuals.

Characterization of a Unique Form of Arrhythmic Cardiomyopathy Caused by Recessive Mutation in LEMD2.

Nuclear envelope proteins have been shown to play an important role in the pathogenesis of inherited dilated cardiomyopathy. Here, we present a remarkable cardiac phenotype caused by a homozygous LEMD2 mutation in patients of the Hutterite population with juvenile cataract. Mutation carriers develop arrhythmic cardiomyopathy with mild impairment of left ventricular systolic function but severe ventricular arrhythmias leading to sudden cardiac death. Affected cardiac tissue from a deceased patient and fibroblasts exhibit elongated nuclei with abnormal condensed heterochromatin at the periphery. The patient fibroblasts demonstrate cellular senescence and reduced proliferation capacity, which may suggest an involvement of LEM domain containing protein 2 in chromatin remodeling processes and premature aging.

Implicit representation of the auditory space: contribution of the left and right hemispheres.

Spatial cues contribute to the ability to segregate sound sources and thus facilitate their detection and recognition. This implicit use of spatial cues can be preserved in cases of cortical spatial deafness, suggesting that partially distinct neural networks underlie the explicit sound localization and the implicit use of spatial cues. We addressed this issue by assessing 40 patients, 20 patients with left and 20 patients with right hemispheric damage, for their ability to use auditory spatial cues implicitly in a paradigm of spatial release from masking (SRM) and explicitly in sound localization. The anatomical correlates of their performance were determined with voxel-based lesion-symptom mapping (VLSM). During the SRM task, the target was always presented at the centre, whereas the masker was presented at the centre or at one of the two lateral positions on the right or left side. The SRM effect was absent in some but not all patients; the inability to perceive the target when the masker was at one of the lateral positions correlated with lesions of the left temporo-parieto-frontal cortex or of the right inferior parietal lobule and the underlying white matter. As previously reported, sound localization depended critically on the right parietal and opercular cortex. Thus, explicit and implicit use of spatial cues depends on at least partially distinct neural networks. Our results suggest that the implicit use may rely on the left-dominant position-linked representation of sound objects, which has been demonstrated in previous EEG and fMRI studies.