Improving Functional Communication Outcomes in Post-Stroke Aphasia via Telepractice: An Alternative Service Delivery Model for Underserved Populations

Many persons with aphasia (PWA) have limited access to speech-language treatment (SLT) due to limited funding, speech-language pathologist shortages, geographical barriers, physical disabilities, transportation barriers, and COVID-19 pandemic. The purpose of this study was to determine if telepractice is an effective and feasible service delivery model for PWA. Ten PWA completed 8 hours of remote treatment over 4 weeks. Synchronous telepractice sessions employed Oral Reading for Language in Aphasia (ORLA) and Conversational Script Training (CST). Pre- and post-assessment outcome measures included the Communication Activities of Daily Living-3 (CADL-3) and the Communication Confidence Rating Scale for Aphasia (CCRSA). Participants completed a telepractice satisfaction survey following post-assessment. All participants demonstrated improvements in CCRSA scores, total words produced correctly on trained CST stimuli, and total words produced correctly on trained ORLA stimuli. No differences were noted in CADL-3 scores. All participants were highly satisfied with telepractice as a service delivery model.

A Simple and Sensitive Method for Measuring Tumor-Specific T Cell Cytotoxicity

A simple and sensitive method to quantitatively measure the cytolytic effect of tumor-specific T killer cells is highly desirable for basic and clinical studies. Chromium (51Cr) release assay has been the “gold standard” for quantifying cytolytic activities of cytotoxic T lymphocytes (CTLs) against target cells and this method is still being used in many laboratories. However, a major drawback of this method is the use of radioactive materials, which is inconvenient to handle because of environmental safety concerns and expensive due to the short half-life of the isotope. Consequently, several nonradioactive methods have been reported recently. Here we report a new method that we recently developed for quantifying antigen-specific cytolytic activity of CTLs. This method fully exploits the high sensitivity and the relative simplicity of luciferase quantitative assay. We initially expected the released luciferase in the supernatant to be the adequate source for monitoring cell death. However, to our total surprise, incubation of these killer T cells with the tumor cell targets did not result in significant release of luciferase in the culture medium. Instead, we found that the remaining luciferase inside the cells could accurately reflect the overall cell viability

Intraflagellar Transport (IFT) Protein IFT25 Is a Phosphoprotein Component of IFT Complex B and Physically Interacts with IFT27 in Chlamydomonas

BACKGROUND: Intraflagellar transport (IFT) is the bidirectional movement of IFT particles between the cell body and the distal tip of a flagellum. Organized into complexes A and B, IFT particles are composed of at least 18 proteins. The function of IFT proteins in flagellar assembly has been extensively investigated. However, much less is known about the molecular mechanism of how IFT is regulated. METHODOLOGY/PRINCIPAL FINDINGS: We herein report the identification of a novel IFT particle protein, IFT25, in Chlamydomonas. Dephosphorylation assay revealed that IFT25 is a phosphoprotein. Biochemical analysis of temperature sensitive IFT mutants indicated that IFT25 is an IFT complex B subunit. In vitro binding assay confirmed that IFT25 binds to IFT27, a Rab-like small GTPase component of the IFT complex B. Immunofluorescence staining showed that IFT25 has a punctuate flagellar distribution as expected for an IFT protein, but displays a unique distribution pattern at the flagellar base. IFT25 co-localizes with IFT27 at the distal-most portion of basal bodies, probably the transition zones, and concentrates in the basal body region by partially overlapping with other IFT complex B subunits, such as IFT46. Sucrose density gradient centrifugation analysis demonstrated that, in flagella, the majority of IFT27 and IFT25 including both phosphorylated and non-phosphorylated forms are cosedimented with other complex B subunits in the 16S fractions. In contrast, in cell body, only a fraction of IFT25 and IFT27 is integrated into the preassembled complex B, and IFT25 detected in complex B is preferentially phosphorylated. CONCLUSION/SIGNIFICANCE: IFT25 is a phosphoprotein component of IFT particle complex B. IFT25 directly interacts with IFT27, and these two proteins likely form a subcomplex in vivo. We postulate that the association and disassociation between the subcomplex of IFT25 and IFT27 and complex B might be involved in the regulation of IFT

Chlamydomonas IFT70/CrDYF-1 Is a Core Component of IFT Particle Complex B and Is Required for Flagellar Assembly

DYF-1 is a highly conserved protein essential for ciliogenesis in several model organisms. In Caenorhabditis elegans, DYF-1 serves as an essential activator for an anterograde motor OSM-3 of intraflagellar transport (IFT), the ciliogenesis-required motility that mediates the transport of flagellar precursors and removal of turnover products. In zebrafish and Tetrahymena DYF-1 influences the cilia tubulin posttranslational modification and may have more ubiquitous function in ciliogenesis than OSM-3. Here we address how DYF-1 biochemically interacts with the IFT machinery by using the model organism Chlamydomonas reinhardtii, in which the anterograde IFT does not depend on OSM-3. Our results show that this protein is a stoichiometric component of the IFT particle complex B and interacts directly with complex B subunit IFT46. In concurrence with the established IFT protein nomenclature, DYF-1 is also named IFT70 after the apparent size of the protein. IFT70/CrDYF-1 is essential for the function of IFT in building the flagellum because the flagella of IFT70/CrDYF-1–depleted cells were greatly shortened. Together, these results demonstrate that IFT70/CrDYF-1 is a canonical subunit of IFT particle complex B and strongly support the hypothesis that the IFT machinery has species- and tissue-specific variations with functional ramifications

Reduction in cell-associated luciferase activity closely reflects the killing activity of T killer cells against tumor targets.

<p>Mock-transduced (<b>A</b>) or cTCR-transduced (<b>B</b>) splenocytes were added to 4T1-Her2 cells at the indicated ratio. Cells were harvested 72 later for quantification of luciferase activity. <b>C</b>. Using the formula: % specific luc reduction = (% luc reduction from engrafted T-cell)/(% luc reduction from control T-cell)×100, the data from <b>A</b> and <b>B</b> were converted into percentage of specific luciferase release and plotted.</p

Potent Functional Immunogenicity of Plasmodium falciparum Transmission-Blocking Antigen (Pfs25) Delivered with Nanoemulsion and Porous Polymeric Nanoparticles

PURPOSE: To evaluate functional immunogenicity of CHrPfs25. a malaria transmission blocking vaccine antigen, using nanoemulsion and porous polymeric PLGA nanoparticles. METHODS: CHrPfs25 was formulated with nanoemulsions (NE) and poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) and evaluated via IM route in mice. Transmission blocking efficacy of antibodies was evaluated by standard mosquito membrane feeding assay using purified IgG from immune sera. Physicochemical properties and stability of various formulations were evaluated by measuring poly-dispersity index, particle size and zeta potential. RESULTS: Mice immunized with CHrPfs25 using alum via IP and IM routes induced comparable immune responses. The highest antibody response was obtained with CHrPfs25 formulated in 4% NE as compared to 8% NE and PLGA-NP. No further increases were observed by combining NE with MPL-A and chitosan. 100% transmission blocking activity was demonstrated at 400 μg/ml of IgG for alum groups (both routes IP and IM), 4% NE and NE-MPL-A. Purified IgG from various adjuvant groups at lower doses (100 μg/mL) still exhibited >90% transmission blocking activity, while 52-81% blocking was seen at 50 μg/mL. CONCLUSION: Results suggest that CHrPfs25 delivered in various adjuvants / nanoparticles elicited strong functional immunogenicity in pre-clinical studies in mice. We are now continuing these studies to develop effective vaccine formulations for further evaluation of immune correlates of relative immunogenicity of CHrPfs25 in various adjuvants and clinical trials

An observation-first strategy for liver injuries with blush on computed tomography is safe and effective.

INTRODUCTION: The management of liver injuries in hemodynamically stable patients is variable and includes primary treatment strategies of observation (OBS), angiography (interventional radiology [IR]) with angioembolization (AE), or operative intervention (OR). We aimed to evaluate the management of patients with liver injuries with active extravasation on computed tomography (CT) imaging, hypothesizing that AE will have more complications without improving outcomes compared with OBS. METHODS: This is a prospective, multicenter, observational study. Patients who underwent CT within 2 hours after arrival with extravasation (e.g., blush) on imaging were included. Exclusion criteria included cirrhosis, nontraumatic hemorrhage, transfers from outside facilities, and pregnancy. No hemodynamic exclusion criteria were used. The primary outcome was liver-specific complications. Secondary outcomes include length of stay and mortality. Angioembolization patients were compared with patients treated without AE. Propensity score matching was used to match based on penetrating mechanism, liver injury severity, arrival vital signs, and early transfusion. RESULTS: Twenty-three centers enrolled 192 patients. Forty percent of patients (n = 77) were initially OBS. Eleven OBS patients (14%) failed nonoperative management and went to IR or OR. Sixty-one patients (32%) were managed with IR, and 42 (69%) of these had AE as an initial intervention. Fifty-four patients (28%) went to OR+/- IR. After propensity score matching (n = 34 per group), there was no difference in baseline characteristics between AE and OBS. The AE group experienced more complications with a higher rate of IR-placed drains for abscess or biloma (22% vs. 0%, p = 0.01) and an increased overall length of stay ( p = 0.01). No difference was noted in transfusions or mortality. CONCLUSION: Observation is highly effective with few requiring additional interventions. Angioembolization was associated with higher rate of secondary drain placement for abscesses or biloma. Given this, a trial of OBS and avoidance of empiric AE may be warranted in hemodynamically stable, liver-injured patient with extravasation on CT. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II