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r the influence of these factors on how we measure, analyze, and conceptualize recovery.

Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA.

We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA.

Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming.

Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items.

White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.

White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.

Stroke is a leading cause of disability worldwide. Focused training of the impaired limb has been shown to improve its functional outcome in animal models. However, most human stroke survivors exhibit persistent motor deficits, likely due to differences in rehabilitation intensity between experimental (animal) and clinical (human) settings.

The current study investigated the effect of training intensity on behavioral outcome in a mouse model of stroke.

Mice were trained preoperatively on a skilled reaching task. After training, mice received a unilateral photothrombotic stroke. Postoperatively, animals received either daily rehabilitative training (traditional intensity), intermittent rehabilitative training (every other day), or no rehabilitative training (control). Assessment of the impaired limb occurred after 14 training sessions (14 days for the Traditional group; 28 days for the Intermittent group).

Assessment of the impaired limb illustrated that traditional, daily training resulted in significten unavailable for human stroke survivors, is necessary to achieve an optimal functional outcome. The lower bounds of training intensity for functional benefit still need to be determined.Physical inactivity is prevalent among ethnic minority women including Korean American (KA) women. We explored the barriers to and facilitators of physical activity (PA) and strategies to promote continued engagement in a PA program with a component of an online community. We conducted a qualitative descriptive study of 37 KA middle-aged women who used to be physically inactive and participated in an exit interview following postintervention visit. Using a thematic analysis approach to analyze the data, we found the individual, interpersonal, and neighborhood/community-level barriers to and facilitators of PA; social influence and social support-related themes were evident. Participants expressed benefit and interest in lifestyle modification using social media. Such program that reduces the barriers and reinforces the facilitators may be able to help motivate KA women to increase their PA.

RUNX1 mutations have been widely found in patients with myelodysplastic syndrome (MDS). Majority of reports revealed that RUNX1 mutations are associated with a poor prognosis. However, discrepancies still remain. The results of univariate analysis were not confirmed in multivariate analysis in some cases. Therefore, we performed a meta-analysis to assess the prognostic effect of RUNX1 mutations in MDS.

We extracted data from qualified studies that were searched from PubMed, Embase and the Cochrane Library. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for the overall survival (OS) and leukemia free survival (LFS) were pooled from the multivariate Cox proportional hazard models.

Sixteen studies containing 5422 patients were included in this meta-analysis. There were 617 patients with mutated RUNX1 and 4805 patients with wide type RUNX1. The total HR for OS was 1.43 (95% CI = 1.21-1.70,

 < 0.0001) and the counterpart of LFS was 1.88 (95% CI = 1.42-2.51,

 < 0.0001).

These results suggest that the RUNX1 mutations are associated with unfavorable outcomes and shorter survival in patients with MDS. Furthermore, poor prognosis of patients might be alleviated by stem cell transplantation. Patients bearing these mutations should be prioritized for aggressive therapy.

These results suggest that the RUNX1 mutations are associated with unfavorable outcomes and shorter survival in patients with MDS. Furthermore, poor prognosis of patients might be alleviated by stem cell transplantation. Patients bearing these mutations should be prioritized for aggressive therapy.

To discuss indications for bilateral auditory brainstem implants (ABIs), compare audiometric outcomes of unilateral vs bilateral ABIs, and determine if patients have improved outcomes with addition of a second-side implant.

Retrospective review of 24 patients with neurofibromatosis 2 (NF2) who underwent sequential placement of ABIs from 1989 to 2019.

Tertiary referral center.

Charts were reviewed for indication for second-side surgery, use of implants, and audiometric outcomes. Implants placed in the past 30 years were included in the study. Northwestern University Children's Perception of Speech (NU-CHIPS) and/or City University of New York (CUNY) sentence scores were compared in unilateral and bilateral conditions.

Indications for a second-side implant included first-side implants with severe nonauditory symptoms (11), marginal audiometric results (9), outdated technology (2), or deterioration of first side (2). Seven patients are bilateral users and 1 patient discontinued bilateral use after a year due to no significant improvement over unilateral use. One patient with initial bilateral use was lost to follow-up. Thirteen patients are unilateral users due to nonaudiometric side effects or poor audiometric outcomes with the first side. Two patients are complete nonusers. Seventy-five percent had improved audiometric outcomes after the second-side implant, and 20% had stable findings.

Second-side ABIs should be consider in patients with poor performance from a first-side implant. Most patients demonstrate subjective improvement with the second ABI. More research is needed for better objective assessments of improvements.

Second-side ABIs should be consider in patients with poor performance from a first-side implant. Most patients demonstrate subjective improvement with the second ABI. More research is needed for better objective assessments of improvements.Eight-segmented, negative-sense, single-stranded genomic RNAs of influenza A virus are terminated with 5' and 3' untranslated regions (UTRs). All segments have highly conserved extremities of 13 and 12 nucleotides at the 5' and 3' UTRs, respectively, constructing the viral RNA (vRNA) promoter. Adjacent to the duplex stem of 3 base pairs (bps) between the two conserved strands, additional 1-4 bps are existing in a segment-specific manner. We investigated the roles of the matrix (M) segment-specific base pair between the 14th nucleotide uridine (U14') of the 5' UTR and the 13th nucleotide adenosine (A13) of the 3' UTR by preparing possible vRNA promoters, named vXY, as well as cRNA promoters, named cYX. We analysed their RNA-dependent RNA replication efficiency using the minigenome replicon system and an enzyme assay system in vitro with synthetic RNA promoters. Notably, in contrast to vAC(s) that is a synthetic vRNA promoter with A14' and C13, base-pair disruption at the complementary RNA (cRNA) promoter in cAC(s), which has A13' and C14, not only reduced viral RNA replication in cells but also impaired de novo initiation of unprimed vRNA synthesis. Reverse genetics experiments confirmatively exhibited that this breakage in the cRNA promoter affected the rescue of infectious virus. The present study suggests that the first segment-specific base pair plays an essential role in generating infectious viruses by regulating the promoter activity of cRNA rather than vRNA. It could provide insights into the role of the segment-specific nucleotides in viral genome replication for sustainable infection.

There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke.

Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3)ed 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51]).

Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS

- NIHSS

= ΔNIHSS

), to examine its relevance to AIS mechanisms and long-term outcomes.

Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS



. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS

was examined. Finally, the association of ΔNIHSS



with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed.

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