Functional effects of an African glucose-6-phosphate dehydrogenase (G6PD) polymorphism (Val68Met) on red blood cell hemolytic propensity and post-transfusion recovery.

BACKGROUND: Donor genetic variation is associated with red blood cell (RBC) storage integrity and post-transfusion recovery. Our previous large-scale genome-wide association study demonstrated that the African G6PD deficient A- variant (rs1050828, Val68Met) is associated with higher oxidative hemolysis after cold storage. Despite a high prevalence of X-linked G6PD mutation in African American population (>10%), blood donors are not routinely screened for G6PD status and its importance in transfusion medicine is relatively understudied. STUDY DESIGN AND METHODS: To further evaluate the functional effects of the G6PD A- mutation, we created a novel mouse model carrying this genetic variant using CRISPR-Cas9. We hypothesize that this humanized G6PD A- variant is associated with reduced G6PD activity with a consequent effect on RBC hemolytic propensity and post-transfusion recovery. RESULTS: G6PD A- RBCs had reduced G6PD protein with ~5% residual enzymatic activity. Significantly increased in vitro hemolysis induced by oxidative stressors was observed in fresh and stored G6PD A- RBCs, along with a lower GSH:GSSG ratio. However, no differences were observed in storage hemolysis, osmotic fragility, mechanical fragility, reticulocytes, and post-transfusion recovery. Interestingly, a 14% reduction of 24-h survival following irradiation was observed in G6PD A- RBCs compared to WT RBCs. Metabolomic assessment of stored G6PD A- RBCs revealed an impaired pentose phosphate pathway (PPP) with increased glycolytic flux, decreasing cellular antioxidant capacity. DISCUSSION: This novel mouse model of the common G6PD A- variant has impaired antioxidant capacity like humans and low G6PD activity may reduce survival of transfused RBCs when irradiation is performed.

Shared Neuroanatomical Substrates for Co-occurring Swallowing and Communication Impairments after Acute Stroke.

INTRODUCTION: Post-stroke dysphagia and communication impairments occur in two-thirds of acute stroke survivors. Identifying the shared neuroanatomical substrate for related impairments could facilitate the development of cross-system therapies. Our purpose was to elucidate discrete brain regions predictive of the combined presence of dysphagia alongside dysarthria and/or aphasia post-stroke. METHODS: We included 40 right (RHS) and 67 left hemisphere (LHS) patients from an acute ischemic stroke cohort with lesions demarcated on diffusion weighted imaging. We undertook binary non-parametric voxel-lesion symptom mapping with a false discovery rate of p <0.05 for co-occurring dysphagia, dysarthria, and aphasia (LHS only). If no voxels survived the threshold, a cluster analysis of >20 voxels involving an uncorrected p <0.01 was applied to identify brain regions associated with the co-occurring impairments. RESULTS: Cluster analyses revealed that dysphagia and dysarthria were associated with insular and superior temporal gyrus (STG) involvement after RHS and with basal ganglia (BG), internal capsule, and thalamic involvement after LHS. Co-occurring dysphagia, dysarthria, and aphasia were associated with BG, STG, and insular cortex involvement. DISCUSSION: Our findings highlight the role of the insula and structures of the BG in co-occurrence patterns involving dysphagia, dysarthria, and aphasia. These newly identified biomarkers may inform new rehabilitation therapeutic targets for treating cross-system functions.

Mindfulness, coping, and optimism as mechanisms of change in the 3RP-NF intervention.

INTRODUCTION: Neurofibromatosis (NF) is chronic neurogenetic condition that increases risk for poor quality of life, depression, and anxiety. Given the lack of biomedical treatments, we developed the "Relaxation Response Resiliency for NF" (3RP-NF) program to improve psychosocial outcomes among adults with NF. OBJECTIVE: To move toward effectiveness testing, we must understand mechanisms that explained treatment effects. We tested whether our hypothesized mechanisms of change-mindfulness, coping, and optimism-mediated improvements in quality of life, depression, and anxiety among adults in the 3RP-NF program (N = 114; ages 18-70; 72.80% female; 81.58% White). METHODS: We conducted mixed-effects models to assess whether these mechanisms uniquely mediated outcomes. RESULTS: Improvements in quality of life were most explained by coping, (b = 0.97, SE = 0.28, CI [0.45, 1.56]), followed by mindfulness (b = 0.46, SE = 0.17, CI [0.15, 0.82]) and optimism (b = 0.39, SE = 0.12, CI [0.17, 0.65]). Improvements in depression and anxiety were most explained by mindfulness (b = -1.52, SE = 0.38, CI [-2.32, -0.85], CSIE = -0.26; b = -1.29, SE = 0.35, CI [-2.04, -0.67], CSIE = -0.23), followed by optimism (b = 0.39, SE = 0.12, CI [0.17, 0.65]; b = -0.49, SE = 0.20, CI [-0.91, -0.13]), but were not explained by coping (b = 0.22, SE = 0.43, CI [-0.62, 1.07]; b = 0.06, SE = 0.46, CI [-0.84, 0.97]), respectively. CONCLUSIONS: Targeting mindfulness, coping, and optimism in psychosocial interventions may be a promising way to improve the lives of adults with NF.

The longitudinal trajectory of discourse from the hyperacute to the chronic phase in mild to moderate poststroke aphasia recovery: A case series study.

BACKGROUND: Discourse analysis has recently received much attention in the aphasia literature. Even if post-stroke language recovery occurs throughout the longitudinal continuum of recovery, very few studies have documented discourse changes from the hyperacute to the chronic phases of recovery. AIMS: To document a multilevel analysis of discourse changes from the hyperacute phase to the chronic phase of post-stroke recovery using a series of single cases study designs. METHODS & PROCEDURES: Four people with mild to moderate post-stroke aphasia underwent four assessments (hyperacute: 0-24 h; acute: 24-72 h; subacute: 7-14 days; and chronic: 6-12 months post-onset). Three discourse tasks were performed at each time point: a picture description, a personal narrative and a story retelling. Multilevel changes in terms of macro- and microstructural aspects were analysed. The results of each discourse task were combined for each time point. Individual effect sizes were computed to evaluate the relative strength of changes in an early and a late recovery time frame. OUTCOMES & RESULTS: Macrostructural results revealed improvements throughout the recovery continuum in terms of coherence and thematic efficiency. Also, the microstructural results demonstrated linguistic output improvement for three out of four participants. Namely, lexical diversity and the number of correct information units/min showed a greater gain in the early compared with the late recovery phase. CONCLUSIONS & IMPLICATIONS: This study highlights the importance of investigating all discourse processing levels as the longitudinal changes in discourse operate differently at each phase of recovery. Overall results support future longitudinal discourse investigation in people with post-stroke aphasia. WHAT THIS PAPER ADDS: What is already known on the subject Multi-level discourse analysis allows for in-depth analysis of underlying discourse processes. To date, very little is known on the longitudinal discourse changes from aphasia onset through to the chronic stage of recovery. This study documents multi-level discourse features in four people with mild to moderate aphasia in the hyperacute, acute, subacute and chronic stage of post-stroke aphasia recovery. What this paper adds to existing knowledge The study found that most discourse variables demonstrated improvement throughout time. Macrostructural variables of coherence and thematic units improved throughout the continuum whereas microstructural variables demonstrated greater gains in the early compared to the late period of recovery. What are the potential or actual clinical implications of this work? This study suggests that multilevel discourse analysis will allow a better understanding of post-stroke aphasia recovery, although more research is needed to determine the clinical utility of these findings. Future research may wish to investigate longitudinal discourse recovery in a larger sample of people with aphasia with heterogenous aphasia profiles and severities.

Measuring communication as a core outcome in aphasia trials: Results of the ROMA-2 international core outcome set development meeting.

BACKGROUND: Evidence-based recommendations for a core outcome set (COS; minimum set of outcomes) for aphasia treatment research have been developed (the Research Outcome Measurement in Aphasia-ROMA, COS). Five recommended core outcome constructs: communication, language, quality of life, emotional well-being and patient-reported satisfaction/impact of treatment, were identified through three international consensus studies. Constructs were paired with outcome measurement instruments (OMIs) during an international consensus meeting (ROMA-1). Before the current study (ROMA-2), agreement had not been reached on OMIs for the constructs of communication or patient-reported satisfaction/impact of treatment. AIM: To establish consensus on a communication OMI for inclusion in the ROMA COS. METHODS & PROCEDURES: Research methods were based on recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Participants with expertise in design and conduct of aphasia trials, measurement instrument development/testing and/or communication outcome measurement were recruited through an open call. Before the consensus meeting, participants agreed on a definition of communication, identified appropriate OMIs, extracted their measurement properties and established criteria for their quality assessment. During the consensus meeting they short-listed OMIs and participants without conflicts of interest voted on the two most highly ranked instruments. Consensus was defined a priori as agreement by ≥ 70% of participants. OUTCOMES & RESULTS: In total, 40 researchers from nine countries participated in ROMA-2 (including four facilitators and three-panel members who participated in pre-meeting activities only). A total of 20 OMIs were identified and evaluated. Eight short-listed communication measures were further evaluated for their measurement properties and ranked. Participants in the consensus meeting (n = 33) who did not have conflicts of interest (n = 29) voted on the top two ranked OMIs: The Scenario Test (TST) and the Communication Activities of Daily Living-3 (CADL-3). TST received 72% (n = 21) of 'yes' votes and the CADL-3 received 28% (n = 8) of 'yes' votes. CONCLUSIONS & IMPLICATIONS: Consensus was achieved that TST was the preferred communication OMI for inclusion in the ROMA COS. It is currently available in the original Dutch version and has been adapted into English, German and Greek. Further consideration must be given to the best way to measure communication in people with mild aphasia. Development of a patient-reported measure for satisfaction with/impact of treatment and multilingual versions of all OMIs of the COS is still required. Implementation of the ROMA COS would improve research outcome measurement and the quality, relevance, transparency, replicability and efficiency of aphasia treatment research. WHAT THIS PAPER ADDS: What is already known on this subject International consensus has been reached on five core constructs to be routinely measured in aphasia treatment studies. International consensus has also been established for OMIs for the three constructs of language, quality of life and emotional well-being. Before this study, OMIs for the constructs of communication and patient-reported satisfaction/impact of treatment were not established. What this paper adds to existing knowledge We gained international consensus on an OMI for the construct of communication. TST is recommended for inclusion in the ROMA COS for routine use in aphasia treatment research. What are the potential or actual clinical implications of this work? The ROMA COS recommends OMIs for a minimum set of outcomes for adults with post-stroke aphasia within phases I-IV aphasia treatment research. Although not intended for clinical use, clinicians may employ the instruments of the ROMA COS, considering the quality of their measurement properties. The systematic inclusion of a measure of communication, such as TST, in clinical practice could ultimately support the implementation of research evidence and best practices.

Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with heart failure with preserved ejection fraction portend a poor prognosis; this phenotype is referred to as combined precapillary and postcapillary pulmonary hypertension (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery (PA) smooth muscle cells. METHODS: We used obese ZSF-1 leptin-receptor knockout rats (heart failure with preserved ejection fraction model), obese ZSF-1 rats treated with SU5416 to stimulate resting pulmonary hypertension (obese+sugen, CpcPH model), and lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated using implanted catheters during treadmill exercise. PA function was evaluated with magnetic resonance imaging and myography. Overexpression of nuclear factor Y α subunit (NFYA), a transcriptional enhancer of sGC ß1 subunit (sGCß1), was performed by PA delivery of adeno-associated virus 6. Treatment groups received the SGLT2 inhibitor empagliflozin in drinking water. PA smooth muscle cells from rats and humans were cultured with palmitic acid, glucose, and insulin to induce metabolic stress. RESULTS: Obese rats showed normal resting right ventricular systolic pressures, which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomic PA remodeling and developed elevated right ventricular systolic pressure at rest, which was exacerbated with exercise, modeling CpcPH. Myography and magnetic resonance imaging during dobutamine challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species and decreased sGCß1 expression. Mechanistically, cultured PA smooth muscle cells from obese rats and humans with diabetes or treated with palmitic acid, glucose, and insulin showed increased mitochondrial reactive oxygen species, which enhanced miR-193b-dependent RNA degradation of nuclear factor Y α subunit (NFYA), resulting in decreased sGCß1-cGMP signaling. Forced NYFA expression by adeno-associated virus 6 delivery increased sGCß1 levels and improved exercise pulmonary hypertension in obese+sugen rats. Treatment of obese+sugen rats with empagliflozin improved metabolic syndrome, reduced mitochondrial reactive oxygen species and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH. CONCLUSIONS: In heart failure with preserved ejection fraction and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced reactive oxygen species and miR-193b expression, which downregulates NFYA-dependent sGCß1 expression. Adeno-associated virus-mediated NFYA overexpression and SGLT2 inhibition restore NFYA-sGCß1-cGMP signaling and ameliorate EIPH.

Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation.

White matter hyperintensities (WMHs) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI-based segmentation methods are often sensitive to acquisition protocols, scanners, noise-level, and image contrast, failing to generalize to other populations and out-of-distribution datasets. Given these concerns, we propose a novel Bayesian 3D convolutional neural network with a U-Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control, and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. Four hundred thirty-two subjects were recruited to train the CNNs from four multisite imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multisite study. We compared our model to two established state-of-the-art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U-Net achieved the highest Dice similarity coefficient of 0.89 ± 0.08 and the lowest modified Hausdorff distance of 2.98 ± 4.40 mm. We further validated our models highlighting their robustness on "clinical adversarial cases" simulating data with low signal-to-noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at: https://hypermapp3r.readthedocs.io.

Description of connected speech across different elicitation tasks in the logopenic variant of primary progressive aphasia.

BACKGROUND: Despite its importance, in-depth analysis of connected speech is often neglected in the diagnosis of primary progressive aphasia (PPA) - especially for the logopenic variant (lvPPA) for which unreliable differential diagnosis has been documented. Only a few studies have been conducted on this topic in lvPPA. AIMS: The aim of this study was to describe and compare lexico-semantic and morphosyntactic features of connected speech in participants with lvPPA, in comparison with healthy controls, using three different elicitation tasks (i.e., picture description, story narration and semi-structured interviews). In addition to a number of discourse features, we were particularly interested in the presence or absence of syntactic deficits in this PPA variant in line with recent findings. METHODS & PROCEDURES: A prospective group study was conducted to compare lvPPA participants (n = 13) to age- and education-matched healthy controls (n = 13). For each individual, connected speech was obtained using three tasks: (1) The Cookie Theft picture description; (2) Cinderella Story; (3) Topic-directed interview. Production on each task was recorded, transcribed and analysed according to the Quantitative Production Analysis (QPA) protocol, a tool developed by Berndt et al. (2000) for the analysis of sentence production in aphasia. Differences between lvPPA and healthy controls and among elicitation tasks were analysed using repeated measures multilevel mixed-effects regression, separately for each outcome. OUTCOMES & RESULTS: Four measures were significantly different between lvPPA participants and healthy controls across all elicitation tasks. Specifically, lvPPA participants produced a reduced proportion of open-class words, a higher proportion of verbs, a higher proportion of pronouns and fewer well-formed sentences. For these measures, the difference between lvPPA and healthy controls was consistent among elicitation tasks, except for the proportion of well-formed sentences, where the difference between the two groups was significantly greater in the story narration task than in the other tasks. CONCLUSIONS & IMPLICATIONS: Across elicitation tasks that used the same analysis protocol (i.e., QPA), a similar pattern of deficits in connected speech emerged in lvPPA patients. Importantly, the findings replicate previous studies, which used different elicitation tasks and analysis protocols. Especially in relation to the documented syntactic deficits, these findings provide implications for differential diagnosis in PPA. WHAT THIS PAPER ADDS: What is already known on the subject Connected speech analysis can provide an important contribution to the language assessment for the logopenic variant of primary progressive aphasia (lvPPA). However, only a few studies have been conducted with this population. What this paper adds to existing knowledge This study highlights differences between patients with lvPPA and healthy controls regarding the proportion of open-class words, nouns, verbs and well-formed sentences. What are the potential or actual clinical implications of this work? Importantly, our results highlight syntactic deficits in the same group of individuals with lvPPA, using the same analysis protocol and across various elicitation tasks, which has implications for differential diagnosis.

BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder characterized by development of high-flow arteriovenous malformations (AVMs) that can lead to stroke or high-output heart failure. HHT2 is caused by heterozygous mutations in ACVRL1, which encodes an endothelial cell bone morphogenetic protein (BMP) receptor, ALK1. BMP9 and BMP10 are established ALK1 ligands. However, the unique and overlapping roles of these ligands remain poorly understood. To define the physiologically relevant ALK1 ligand(s) required for vascular development and maintenance, we generated zebrafish harboring mutations in bmp9 and duplicate BMP10 paralogs, bmp10 and bmp10-like. bmp9 mutants survive to adulthood with no overt phenotype. In contrast, combined loss of bmp10 and bmp10-like results in embryonic lethal cranial AVMs indistinguishable from acvrl1 mutants. However, despite embryonic functional redundancy of bmp10 and bmp10-like, bmp10 encodes the only required Alk1 ligand in the juvenile-to-adult period. bmp10 mutants exhibit blood vessel abnormalities in anterior skin and liver, heart dysmorphology, and premature death, and vascular defects correlate with increased cardiac output. Together, our findings support a unique role for Bmp10 as a non-redundant Alk1 ligand required to maintain the post-embryonic vasculature and establish zebrafish bmp10 mutants as a model for AVM-associated high-output heart failure, which is an increasingly recognized complication of severe liver involvement in HHT2.

Episodic memory decline is associated with deficits in coherence of discourse.

This study investigates coherence of discourse in the production of autobiographical narratives by individuals with aMCI. Autobiographical interviews were analyzed to determine whether reduced episodic recall was related to deficits in discourse coherence. A coherence rating scale was used to evaluate relatedness of the autobiographical details produced by participants to the topic of discourse. Interviews were transcribed, segmented into details, and divided into sets of episodic, semantic, or supplementary information, which were subsequently analysed with the coherence rating scale. We predicted that the known episodic deficits observed in aMCI could also affect the retrieval of coherent episodic information. The results revealed deficits in coherence could be found in both episodic and semantic information in the aMCI group. These results suggest that the cognitive deficits experienced by individuals with aMCI may go beyond their known difficulty in recalling episodic details, as they also affect the controlled retrieval of both episodic and semantic information.

The role of executive control in post-stroke aphasia treatment.

Executive control (EC) ability is increasingly emerging as an important predictor of post-stroke aphasia recovery. This study examined whether EC predicted immediate treatment gains, treatment maintenance and generalization after naming therapy in ten adults with mild to severe chronic post-stroke aphasia. Performance on multiple EC tasks allowed for the creation of composite scores for common EC, and the EC processes of shifting, inhibition and working memory (WM) updating. Participants were treated three times a week for five weeks with a phonological naming therapy; difference scores in naming accuracy of treated and untreated words (assessed pre, post, four- and eight-weeks after therapy) served as the primary outcome measures. Results from simple and multiple linear regressions indicate that individuals with better shifting and WM updating abilities demonstrated better maintenance of treated words at four-week follow-up, and those with better common EC demonstrated better maintenance of treated words at both four- and eight-week follow-ups. Better shifting ability also predicted better generalization to untreated words post-therapy. Measures of EC were not indicative of improvements on treated words immediately post-treatment, nor of generalization to untreated words at follow-up. Findings suggest that immediate treatment gains, maintenance and generalization may be supported by different underlying mechanisms.

Oral care practices of long-term care home residents and caregivers: Secondary analysis of observational video recordings.

AIMS AND OBJECTIVES: To describe the proportion of toothbrushing task steps, long-term care residents had an opportunity to complete; the duration and quality of toothbrushing by both residents and caregivers; and the feedback caregivers provided. BACKGROUND: Poor oral health is widespread among older adults in long-term care homes; however, little is known about their actual oral health practices. DESIGN: Secondary analysis of video recordings. METHODS: A total of 58 video-recorded sessions were analysed from two long-term care homes in Canada. Eligible residents had at least one natural tooth, required oral care assistance, had Alzheimer's disease and understood English. Eligible caregivers spoke English and had worked for at least 1 year with people with dementia. Toothbrushing success was identified by the resident's participation in, and completion of, nine toothbrushing steps. Total time spent brushing teeth was calculated by summing the duration of time spent brushing teeth. Quality was described by time spent brushing the facial versus the lingual or occlusal surfaces. Caregiver verbal feedback was pulled from transcripts and analysed using content analysis. STROBE guidelines were used in reporting this study. RESULTS: The two step residents most frequently completed or attempted were brushing their teeth (77% complete, 7% attempt) and rinsing their mouth (86% complete, 2% attempt). The average time spent brushing teeth was 60.33 s (SD = 35.15). In 66% of observed videos, toothbrushing occurred only on the facial tooth surfaces, with no time spent brushing the lingual or occlusal surfaces. CONCLUSION: Caregivers are supporting residents to independently complete toothbrushing; however, the duration and quality of toothbrushing are not sufficient to ensure optimal oral health. RELEVANCE TO CLINICAL PRACTICE: Clear, detailed guidelines are required to ensure adequate oral care for long-term care residents. Staff need to be aware that all surfaces should be brushed to ensure proper oral health.

Alk1 controls arterial endothelial cell migration in lumenized vessels.

Heterozygous loss of the arterial-specific TGFß type I receptor, activin receptor-like kinase 1 (ALK1; ACVRL1), causes hereditary hemorrhagic telangiectasia (HHT). HHT is characterized by development of fragile, direct connections between arteries and veins, or arteriovenous malformations (AVMs). However, how decreased ALK1 signaling leads to AVMs is unknown. To understand the cellular mis-steps that cause AVMs, we assessed endothelial cell behavior in alk1-deficient zebrafish embryos, which develop cranial AVMs. Our data demonstrate that alk1 loss has no effect on arterial endothelial cell proliferation but alters arterial endothelial cell migration within lumenized vessels. In wild-type embryos, alk1-positive cranial arterial endothelial cells generally migrate towards the heart, against the direction of blood flow, with some cells incorporating into endocardium. In alk1-deficient embryos, migration against flow is dampened and migration in the direction of flow is enhanced. Altered migration results in decreased endothelial cell number in arterial segments proximal to the heart and increased endothelial cell number in arterial segments distal to the heart. We speculate that the consequent increase in distal arterial caliber and hemodynamic load precipitates the flow-dependent development of downstream AVMs.

Baseline executive control ability and its relationship to language therapy improvements in post-stroke aphasia: a systematic review.

PURPOSE: To review current evidence on the relationship between executive control (EC) and post-treatment language gains in adults with post-stroke aphasia. METHOD: Electronic databases (CINAHL, Cochrane Trials, Embase, MEDLINE, MEDLINE-in-Process and PsycINFO) were systematically searched (year 2000 - present). Abstracts and full-text articles were reviewed by two independent raters against pre-specified criteria: original research with N > 2; at least 90% adults with stroke, all undergoing treatment for acquired aphasia; pre-treatment EC abilities were compared to language gains post-treatment across studies. Critical appraisal was conducted using the Cochrane group and Single-Case Experimental Design (SCED) methods. Data were extracted and summarised descriptively. RESULTS: Search results yielded 2272 unique citations; ultimately 15 studies were accepted for review. Both pre-treatment EC and language abilities appear to be important indicators of treatment success, especially in moderate-severe aphasia. This relationship emerged when EC was measured using specific (e.g., divided attention), as opposed to broad (e.g., reasoning) tasks, and primarily when naming therapy was administered; intensive constraint-induced therapy did not correlate with treatment success. CONCLUSIONS: EC is a promising prognostic variable regarding language recovery, but further research is required using a-priori declared theoretical EC models, along with properly powered samples, standardised EC tasks and treatment protocols.

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.

The effects of an interprofessional patient-centered communication intervention for patients with communication disorders.

PURPOSE OF THE STUDY: This small scale study examined the influence of an interprofessional (IP) evidence based patient-centered communication intervention (PCCI), delivered by trained nurses in collaboration with Speech Language Pathologists, on patient outcomes in an active stroke rehabilitation setting. DESIGN AND METHODS: The setting constraints imposed the use of a single-group pretest and post-test design to determine the influence of the intervention on patient outcomes. Validated tools measured patient quality of life (QOL), depressive symptoms and satisfaction with care. RESULTS: Patients (n=34) showed improvement in all outcomes from pretest to post-test, including quality of life, geriatric depressive symptoms, and satisfaction with care. IMPLICATIONS: The findings indicate that a comprehensive person-centered communication intervention has the potential to enhance patient outcomes at discharge. Challenges to implementing and evaluating evidence-based interventions in practice are highlighted.

Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKI.

Retinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.

Wh- questions and passive sentences in non-fluent variant PPA and semantic variant PPA: Longitudinal findings of an anagram production task.

Using an anagram task, we investigated longitudinal syntactic production by individuals with semantic variant primary progressive aphasia (svPPA) and non-fluent variant PPA (nfvPPA), compared to controls. The accuracy of the production of active and passive, and reversible and non-reversible sentences, as well as of wh- questions was compared across the three groups. Results showed a different pattern of syntactic impairment across the two patient groups. The nfvPPA group showed difficulty with wh- questions at Time 1 and impairment with the passive structure approximately one year later, at Time 2. Surprisingly, the svPPA group also showed difficulty with wh- questions from Time 1, but still no difficulty on passive sentences, two years later, at Time 3. Neither group had difficulty with reversibility. The results of the nfvPPA patients were as expected, and the results of the svPPA patients suggest that this group may exhibit a greater syntactic impairment than is typically recognized.

Poststroke Aphasia Frequency, Recovery, and Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVES: To conduct a systematic review to elucidate the frequency, recovery, and associated outcomes for poststroke aphasia over the long-term. DATA SOURCES: Using the Cochrane Stroke Strategy, we searched 10 databases, 13 journals, 3 conferences, and the gray literature. STUDY SELECTION: Our a priori protocol criteria included unselected samples of adult stroke patients from randomized controlled trials or consecutive cohorts. Two independent reviewers rated abstracts and articles for exclusion or inclusion, resolving discrepancies by consensus. DATA EXTRACTION: We documented aphasia frequencies by stroke type and setting, and computed odds ratios (ORs) with their 95% confidence intervals (CIs) for outcomes. DATA SYNTHESIS: We retrieved 2168 citations, reviewed 248 articles, and accepted 50. Median frequencies for mixed stroke (ischemic and hemorrhagic) were 30% and 34% for acute and rehabilitation settings, respectively. Frequencies by stroke type were lowest for acute subarachnoid hemorrhage (9%) and highest for acute ischemic stroke (62%) when arrival to the hospital was ≤3 hours from stroke onset. Articles monitoring aphasia for 1 year demonstrated aphasia frequencies 2% to 12% lower than baseline. Negative outcomes associated with aphasia included greater odds of in-hospital death (OR=2.7; 95% CI, 2.4-3.1) and longer mean length of stay in days (mean=1.6; 95% CI, 1.0-2.3) in acute settings. Patients with aphasia had greater disability from 28 days (OR=1.5; 95% CI, 1.3-1.7) to 2 years (OR=1.7; 95% CI, 1.6-2.0) than those without aphasia. By 2 years, they used more rehabilitation services (OR=1.5; 95% CI, 1.3-1.6) and returned home less frequently (OR=1.4; 95% CI, 1.2-1.7). CONCLUSIONS: Reported frequencies of poststroke aphasia range widely, depending on stroke type and setting. Because aphasia is associated with mortality, disability, and use of health services, we recommend long-term interdisciplinary vigilance in the management of aphasia.