Illuminating protein space with a programmable generative model.

Three billion years of evolution has produced a tremendous diversity of protein molecules1, but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larger than the space of those likely to have functions. Here we introduce Chroma, a generative model for proteins and protein complexes that can directly sample novel protein structures and sequences, and that can be conditioned to steer the generative process towards desired properties and functions. To enable this, we introduce a diffusion process that respects the conformational statistics of polymer ensembles, an efficient neural architecture for molecular systems that enables long-range reasoning with sub-quadratic scaling, layers for efficiently synthesizing three-dimensional structures of proteins from predicted inter-residue geometries and a general low-temperature sampling algorithm for diffusion models. Chroma achieves protein design as Bayesian inference under external constraints, which can involve symmetries, substructure, shape, semantics and even natural-language prompts. The experimental characterization of 310 proteins shows that sampling from Chroma results in proteins that are highly expressed, fold and have favourable biophysical properties. The crystal structures of two designed proteins exhibit atomistic agreement with Chroma samples (a backbone root-mean-square deviation of around 1.0 Å). With this unified approach to protein design, we hope to accelerate the programming of protein matter to benefit human health, materials science and synthetic biology.

Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment.

OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.

Association of mycophenolate and azathioprine use with cognitive function in systemic lupus.

OBJECTIVES: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. METHODS: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. RESULTS: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. CONCLUSION: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Misfolded α-Synuclein in Cerebrospinal Fluid of Contact Sport Athletes.

BACKGROUND: Misfolded α-synuclein in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) can be detected using the real-time quaking-induced conversion (RT-QuIC) technique in cerebrospinal fluid (CSF). OBJECTIVES: The objectives are (1) to examine misfolded CSF α-synuclein incidence, and (2) to compare clinical presentation, sports history, brain volumes, and RT-QuIC α-synuclein positivity in former athletes. METHODS: Thirty former athletes with magnetic resonance imaging, neuropsychological testing, and CSF analyzed for phosphorylated tau 181 (p-tau), total tau (t-tau), amyloid-ß 42 (Aß42), and neurofilament light chain (NfL). CSF α-synuclein was detected using RT-QuIC. RESULTS: Six (20%) former athletes were α-synuclein positive. α-Synuclein positive athletes were similar to α-synuclein negative athletes on demographics, sports history, clinical features, CSF p-tau, t-tau, Aß42, and NfL; however, had lower grey matter volumes in the right inferior orbitofrontal, right anterior insula and right olfactory cortices. CONCLUSIONS: α-Synuclein RT-QuIC analysis of CSF may be useful as a prodromal biofluid marker of PD and DLB. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Metabolic excretion associated with nutrient-growth dysregulation promotes the rapid evolution of an overt metabolic defect.

In eukaryotes, conserved mechanisms ensure that cell growth is coordinated with nutrient availability. Overactive growth during nutrient limitation ("nutrient-growth dysregulation") can lead to rapid cell death. Here, we demonstrate that cells can adapt to nutrient-growth dysregulation by evolving major metabolic defects. Specifically, when yeast lysine-auxotrophic mutant lys- encountered lysine limitation, an evolutionarily novel stress, cells suffered nutrient-growth dysregulation. A subpopulation repeatedly evolved to lose the ability to synthesize organosulfurs (lys-orgS-). Organosulfurs, mainly reduced glutathione (GSH) and GSH conjugates, were released by lys- cells during lysine limitation when growth was dysregulated, but not during glucose limitation when growth was regulated. Limiting organosulfurs conferred a frequency-dependent fitness advantage to lys-orgS- by eliciting a proper slow growth program, including autophagy. Thus, nutrient-growth dysregulation is associated with rapid organosulfur release, which enables the selection of organosulfur auxotrophy to better tune cell growth to the metabolic environment. We speculate that evolutionarily novel stresses can trigger atypical release of certain metabolites, setting the stage for the evolution of new ecological interactions.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part III: Executive Functions.

INTRODUCTION: Moderate-to-severe traumatic brain injury (MS-TBI) causes debilitating and enduring impairments of executive functioning and self-awareness, which clinicians often find challenging to address. Here, we provide an update to the INCOG 2014 guidelines for the clinical management of these impairments. METHODS: An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated recommendations for the management of executive functioning and self-awareness post-MS-TBI, as well as a decision-making algorithm, and an audit tool for review of clinical practice. RESULTS: A total of 8 recommendations are provided regarding executive functioning and self-awareness. Since INCOG 2014, 4 new recommendations were made and 4 were modified and updated from previous recommendations. Six recommendations are based on level A evidence, and 2 are based on level C. Recommendations retained from the previous guidelines and updated, where new evidence was available, focus on enhancement of self-awareness (eg, feedback to increase self-monitoring; training with video-feedback), meta-cognitive strategy instruction (eg, goal management training), enhancement of reasoning skills, and group-based treatments. New recommendations addressing music therapy, virtual therapy, telerehabilitation-delivered metacognitive strategies, and caution regarding other group-based telerehabilitation (due to a lack of evidence) have been made. CONCLUSIONS: Effective management of impairments in executive functioning can increase the success and well-being of individuals with MS-TBI in their day-to-day lives. These guidelines provide management recommendations based on the latest evidence, with support for their implementation, and encourage researchers to explore and validate additional factors such as predictors of treatment response.

Psychosocial impacts of the COVID-19 pandemic on women with trauma histories: Study of Women's Health Across the Nation (SWAN).

Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.

Preliminary efficacy and predictors of response to a remotely-delivered symptom self-management program for persistent symptoms after concussion.

BACKGROUND: More than a quarter of adults with concussion endure prolonged symptoms of >3 months. We developed the Concussion Education Self-Management program to help people manage persisting symptoms. Here, we assess feasibility, preliminary efficacy, and correlates of response. METHODS: N = 80 adults participated in the program; ages ranged from 18 to 65 years and time post-injury ranged from 6 months to 18 years. Weekly sessions, delivered remotely and in groups, comprised education and strategies for management of cognitive, emotional, and physical symptoms. Primary outcome: Confidence to self-manage symptoms. Secondary outcomes: Quality of life; mood/anxiety/stress. Predictors of response: Self-reported cognitive, emotional and physical symptoms at intake. RESULTS: Pre- to post-program improvements were observed in confidence to self-manage, p < 0.03; quality of life, p < 0.001; depression, p < 0.001; anxiety, p < 0.001; and stress, p < 0.001. Considering confidence to self-manage, those with fewer cognitive and physical symptoms benefitted more (p's < 0.0005 and p < 0.01, respectively). DISCUSSION: This program shows promise for improving self-management of prolonged symptoms. Those with high symptom burden may need extra sessions to benefit. This is a cost-effective and scalable program that can reach people regardless of geographic location or impediments to travel.

Towards PPG-based anger detection for emotion regulation.

BACKGROUND: Anger dyscontrol is a common issue after traumatic brain injury (TBI). With the growth of wearable physiological sensors, there is new potential to facilitate the rehabilitation of such anger in the context of daily life. This potential, however, depends on how well physiological markers can distinguish changing emotional states and for such markers to generalize to real-world settings. Our study explores how wearable photoplethysmography (PPG), one of the most widely available physiological sensors, could be used detect anger within a heterogeneous population. METHODS: This study collected the TRIEP (Toronto Rehabilitation Institute Emotion-Physiology) dataset, which comprised of 32 individuals (10 TBI), exposed to a variety of elicitation material (film, pictures, self-statements, personal recall), over two day sessions. This complex dataset allowed for exploration into how the emotion-PPG relationship varied over changes in individuals, endogenous/exogenous drivers of emotion, and day-to-day differences. A multi-stage analysis was conducted looking at: (1) times-series visual clustering, (2) discriminative time-interval features of anger, and (3) out-of-sample anger classification. RESULTS: Characteristics of PPG are largely dominated by inter-subject (between individuals) differences first, then intra-subject (day-to-day) changes, before differentiation into emotion. Both TBI and non-TBI individuals showed evidence of linear separable features that could differentiate anger from non-anger classes within time-interval analysis. However, what is more challenging is that these separable features for anger have various degrees of stability across individuals and days. CONCLUSION: This work highlights how there are contextual, non-stationary challenges to the emotion-physiology relationship that must be accounted for before emotion regulation technology can perform in real-world scenarios. It also affirms the need for a larger breadth of emotional sampling when building classification models.

Patterns of change in cortical morphometry following traumatic brain injury in adults.

Progressive cortical volumetric loss following moderate-severe traumatic brain injury (TBI) has been observed; however, regionally specific changes in the structural determinants of cortical volume, namely, cortical thickness (CT) and cortical surface area (CSA), are unknown and may inform the patterns and neural substrates of neurodegeneration and plasticity following injury. We aimed to (a) assess differences in CT and CSA between TBI participants and controls in the early chronic stage post-injury, (b) describe longitudinal changes in cortical morphometry following TBI, and (c) examine how regional changes in CT and CSA are associated. We acquired magnetic resonance images for 67 participants with TBI at up to 4 time-points spanning 5 months to 7 years post-injury, and 18 controls at 2 time-points. In the early chronic stage, TBI participants displayed thinner cortices than controls, predominantly in frontal regions, but no CSA differences. Throughout the chronic period, TBI participants showed widespread CT reductions in posterior cingulate/precuneus regions and moderate CT increase in frontal regions. Additionally, CSA showed a significant decrease in the orbitofrontal cortex and circumscribed increase in posterior regions. No changes were identified in controls. Relationships between regional cortical changes in the same morphological measure revealed coordinated patterns within participants, whereas correlations between regions with CT and CSA change yielded bi-directional relationships. This suggests that these measures may be differentially affected by neurodegenerative mechanisms such as transneuronal degeneration following TBI and that degeneration may be localized to the depths of cortical sulci. These findings emphasize the importance of dissecting morphometric contributions to cortical volume change.

Uncovering and resolving challenges of quantitative modeling in a simplified community of interacting cells.

Quantitative modeling is useful for predicting behaviors of a system and for rationally constructing or modifying the system. The predictive power of a model relies on accurate quantification of model parameters. Here, we illustrate challenges in parameter quantification and offer means to overcome these challenges, using a case example in which we quantitatively predict the growth rate of a cooperative community. Specifically, the community consists of two Saccharomyces cerevisiae strains, each engineered to release a metabolite required and consumed by its partner. The initial model, employing parameters measured in batch monocultures with zero or excess metabolite, failed to quantitatively predict experimental results. To resolve the model-experiment discrepancy, we chemically identified the correct exchanged metabolites, but this did not improve model performance. We then remeasured strain phenotypes in chemostats mimicking the metabolite-limited community environments, while mitigating or incorporating effects of rapid evolution. Almost all phenotypes we measured, including death rate, metabolite release rate, and the amount of metabolite consumed per cell birth, varied significantly with the metabolite environment. Once we used parameters measured in a range of community-like chemostat environments, prediction quantitatively agreed with experimental results. In summary, using a simplified community, we uncovered and devised means to resolve modeling challenges that are likely general to living systems.

Validation of the automated neuropsychological assessment metrics for assessing cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis. METHODS: 300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs. RESULTS: Two models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results. CONCLUSION: We provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury.

OBJECTIVE: To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury. PARTICIPANTS: Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI. METHODS: Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest. RESULTS: (1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time. CONCLUSION: Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.

Criterion validity of the brief test of adult cognition by telephone (BTACT) for mild traumatic brain injury.

OBJECTIVES: There is a growing demand for remote assessment options for measuring cognition after mild traumatic brain injury (mTBI). The current study evaluated the criterion validity of the Brief Test of Adult Cognition by Telephone (BTACT) in distinguishing between adults with mTBI and trauma controls (TC) who sustained injuries not involving the head or neck. METHODS: The BTACT was administered to the mTBI (n = 46) and TC (n = 35) groups at 1-2 weeks post-injury. Participants also completed the Rivermead Post Concussion Symptoms Questionnaire. RESULTS: The BTACT global composite score did not significantly differ between the groups (t(79) = -1.04, p = 0.30); the effect size was small (d = 0.23). In receiver operating characteristic curve analyses, the BTACT demonstrated poor accuracy in differentiating between the groups (AUC = 0.567, SE = 0.065, 95% CI [0.44, 0.69]). The BTACT's ability to discriminate between mTBI and TCs did not improve after excluding mTBI participants (n = 15) who denied ongoing cognitive symptoms (AUC = 0.567, SE = 0.072, 95% CI [0.43, 0.71]). CONCLUSIONS: The BTACT may lack sensitivity to subacute cognitive impairment attributable to mTBI (i.e., not explained by bodily pain, post-traumatic stress, and other nonspecific effects of injury).

The impact of cytokine levels in young South African children with and without HIV-associated acute lower respiratory infections.

Altered host immune responses are considered to play a key role in the pathogenesis of acute lower respiratory infections (ALRI). The existing literature on cytokine responses in ALRI is largely focussed on adults from developed countries and there are few reports describing the role of cytokines in childhood ALRI, particularly in African or human immunodeficiency virus (HIV)-infected populations. To measure systemic cytokine levels in blood plasma from young South African children with and without ALRI and with and without HIV to determine associations between cytokine responses and disease status and respiratory viral identification. Blood plasma samples were collected from 106 hospitalized ALRI cases and 54 non-ALRI controls less than 2 years of age. HIV status was determined. Blood plasma concentrations of 19 cytokines, 7 chemokines, and 4 growth factors (epidermal growth factor, fibroblast growth factor-basic, hepatocyte growth factor, and vascular endothelial) were measured using The Human Cytokine 30-Plex Panel. Common respiratory viruses were identified by PCR. Mean cytokine concentrations for G-CSF, interferon (IFN)-γ, interleukin (IL)-5, and MCP-1 were significantly higher in ALRI cases than in nonrespiratory controls. Within the ALRI cases, several cytokines were higher in children with a virus compared with children without a virus. Mean cytokine concentrations for IFN-α, IFN-γ, IL-4, IL-5, IL-13, tumour necrosis factor-α, and MIP-1α were significantly lower in HIV-infected cases than in HIV-uninfected cases, while IP-10 and monokine induced by interferon-γ were significantly higher in HIV-infected cases than in HIV-uninfected cases. Certain cytokines are likely to play an important role in the host immune response to ALRI. HIV-infected children have impaired inflammatory responses to respiratory infections compared with HIV-uninfected children.

Pediatric Index of Mortality 3-An Evaluation of Function Among ICUs In South Africa.

OBJECTIVES: To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model. DESIGN: This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay. SETTING: Nine units that care for children within tertiary or quaternary academic hospitals in South Africa. PATIENTS: All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6-59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79-0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients. CONCLUSIONS: The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.

The psychological burden of waiting for procedures and patient-centred strategies that could support the mental health of wait-listed patients and caregivers during the COVID-19 pandemic: A scoping review.

BACKGROUND: Waiting for procedures delayed by COVID-19 may cause anxiety and related adverse consequences. OBJECTIVE: To synthesize research on the mental health impact of waiting and patient-centred mitigation strategies that could be applied in the COVID-19 context. METHODS: Using a scoping review approach, we searched 9 databases for studies on waiting lists and mental health and reported study characteristics, impacts and intervention attributes and outcomes. RESULTS: We included 51 studies that focussed on organ transplant (60.8%), surgery (21.6%) or cancer management (13.7%). Most patients and caregivers reported anxiety, depression and poor quality of life, which deteriorated with increasing wait time. The impact of waiting on mental health was greater among women and new immigrants, and those of younger age, lower socio-economic status, or with less-positive coping ability. Six studies evaluated educational strategies to develop coping skills: 2 reduced depression (2 did not), 1 reduced anxiety (2 did not) and 2 improved quality of life (2 did not). In contrast, patients desired acknowledgement of concerns, peer support, and periodic communication about wait-list position, prioritization criteria and anticipated procedure date. CONCLUSIONS: Findings revealed patient-centred strategies to alleviate the mental health impact of waiting for procedures. Ongoing research should explore how to optimize the impact of those strategies for diverse patients and caregivers, particularly in the COVID-19 context. PATIENT OR PUBLIC CONTRIBUTION: Six patients and four caregivers waiting for COVID-19-delayed procedures helped to establish eligibility criteria, plan data extraction and review a draft and final report.

Systematic Review of Measurement Property Evidence for 8 Financial Management Instruments in Populations With Acquired Cognitive Impairment.

OBJECTIVES: To critically appraise the measurement property evidence (ie, psychometric) for 8 observation-based financial management assessment instruments. DATA SOURCES: Seven databases were searched in May 2015. STUDY SELECTION: Two reviewers used an independent decision-agreement process to select studies of measurement property evidence relevant to populations with adulthood acquired cognitive impairment, appraise the quality of the evidence, and extract data. Twenty-one articles were selected. DATA EXTRACTION: This review used the COnsensus-based Standards for the selection of health Measurement Instruments review guidelines and 4-point tool to appraise evidence. After appraising the methodologic quality, the adequacy of results and volume of evidence per instrument were synthesized. Measurement property evidence with high risk of bias was excluded from the synthesis. DATA SYNTHESIS: The volume of measurement property evidence per instrument is low; most instruments had 1 to 3 included studies. Many included studies had poor methodologic quality per measurement property evidence area examined. Six of the 8 instruments reviewed had supporting construct validity/hypothesis-testing evidence of fair methodologic quality. There is a dearth of acceptable quality content validity, reliability, and responsiveness evidence for all 8 instruments. CONCLUSIONS: Rehabilitation practitioners assess financial management functions in adults with acquired cognitive impairments. However, there is limited published evidence to support using any of the reviewed instruments. Practitioners should exercise caution when interpreting the results of these instruments. This review highlights the importance of appraising the quality of measurement property evidence before examining the adequacy of the results and synthesizing the evidence.

The lung microbiome in children with HIV-bronchiectasis: a cross-sectional pilot study.

BACKGROUND: Data on the lung microbiome in HIV-infected children is limited. The current study sought to determine the lung microbiome in HIV-associated bronchiectasis and to assess its association with pulmonary exacerbations. METHODS: A cross-sectional pilot study of 22 children (68% male; mean age 10.8 years) with HIV-associated bronchiectasis and a control group of 5 children with cystic fibrosis (CF). Thirty-one samples were collected, with 11 during exacerbations. Sputum samples were processed with 16S rRNA pyrosequencing. RESULTS: The average number of operational taxonomy units (OTUs) was 298 ± 67 vs. 434 ± 90, for HIV-bronchiectasis and CF, respectively. The relative abundance of Proteobacteria was higher in HIV-bronchiectasis (72.3%), with only 22.2% Firmicutes. There was no correlation between lung functions (FEV1% and FEF25/75%) and bacterial community (r = 0.154; p = 0.470 and r = 0.178; p = 0.403), respectively. Bacterial assemblage of exacerbation and non-exacerbation samples in HIV-bronchiectasis was not significantly different (ANOSIM, RHIV-bronchiectasis = 0.08; p = 0.14 and RCF = 0.08, p = 0.50). Higher within-community heterogeneity and lower evenness was associated with CF (Shannon-Weiner (H') = 5.39 ± 0.38 and Pielou's evenness (J) 0.79 ± 0.10 vs. HIV-bronchiectasis (Shannon-Weiner (H') = 4.45 ± 0.49 and Pielou's (J) 0.89 ± 0.03. CONCLUSION: The microbiome in children with HIV-associated bronchiectasis seems to be less rich, diverse and heterogeneous with predominance of Proteobacteria when compared to cystic fibrosis.

Changes in Resting-State Connectivity following Melody-Based Therapy in a Patient with Aphasia.

Melody-based treatments for patients with aphasia rely on the notion of preserved musical abilities in the RH, following left hemisphere damage. However, despite evidence for their effectiveness, the role of the RH is still an open question. We measured changes in resting-state functional connectivity following melody-based intervention, to identify lateralization of treatment-related changes. A patient with aphasia due to left frontal and temporal hemorrhages following traumatic brain injuries (TBI) more than three years earlier received 48 sessions of melody-based intervention. Behavioral measures improved and were maintained at the 8-week posttreatment follow-up. Resting-state fMRI data collected before and after treatment showed an increase in connectivity between motor speech control areas (bilateral supplementary motor areas and insulae) and RH language areas (inferior frontal gyrus pars triangularis and pars opercularis). This change, which was specific for the RH, was greater than changes in a baseline interval measured before treatment. No changes in RH connectivity were found in a matched control TBI patient scanned at the same intervals. These results are compatible with a compensatory role for RH language areas following melody-based intervention. They further suggest that this therapy intervenes at the level of the interface between language areas and speech motor control areas necessary for language production.