Effectiveness of Domain-Based Intervention for Language Development in Japanese Hearing-Impaired Children: A Multicenter Study

Objective: Decreasing language delay in hearing-impaired children is a key issue in the maintenance of their quality of life. Language training has been presented mainly by experience-based training; effective intervention programs are crucially important for their future. The aim of this study was to confirm the efficacy of 6-month domain-based language training of school-age, severe-to-profound hearing-impaired children. Methods: We conducted a controlled before-after study involving 728 severe-to-profound prelingual hearing-impaired children, including an intervention group (n = 60), control group (n = 30), and baseline study group (n = 638). Language scores of the participants and questionnaires to the caregivers/therapists were compared before and after the intervention. Average monthly increase in each language score of the control group and baseline study group were compared with those of the intervention group. Results: Language scores and the results of the questionnaire of the intervention group showed a significant improvement (P < .05). The average monthly language growth of the intervention group was twice that of the control group and 3 to 4 times that of the baseline study group (P < .05). The effect size was largest in communication (1.914), followed by syntax (0.931). Conclusion: Domain-based language training improved the language development and daily communication of hearing-impaired children without any adverse effects

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial.

PURPOSE:To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).METHODS:Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.RESULTS:Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.CONCLUSIONS:IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02305238

Early Detection of Abnormal Prion Protein in Genetic Human Prion Diseases Now Possible Using Real-Time QUIC Assay

Introduction: The definitive diagnosis of genetic prion diseases (gPrD) requires pathological confirmation. To date, diagnosis has relied upon the finding of the biomarkers 14-3-3 protein and total tau (t-tau) protein in the cerebrospinal fluid (CSF), but many researchers have reported that these markers are not sufficiently elevated in gPrD, especially in Gerstmann-Sträussler-Scheinker syndrome (GSS). We recently developed a new in vitro amplification technology, designated "real-time quaking-induced conversion (RT-QUIC)", to detect the abnormal form of prion protein in CSF from sporadic Creutzfeldt-Jakob disease (sCJD) patients. In the present study, we aimed to investigate the presence of biomarkers and evaluate RT-QUIC assay in patients with gPrD, as the utility of RT-QUIC as a diagnostic tool in gPrD has yet to be determined. Method/Principal Findings: 56 CSF samples were obtained from gPrD patients, including 20 cases of GSS with P102L mutation, 12 cases of fatal familial insomnia (FFI; D178N), and 24 cases of genetic CJD (gCJD), comprising 22 cases with E200K mutation and 2 with V203I mutation. We subjected all CSF samples to RT-QUIC assay, analyzed 14-3-3 protein by Western blotting, and measured t-tau protein using an ELISA kit. The detection sensitivities of RT-QUIC were as follows: GSS (78%), FFI (100%), gCJD E200K (87%), and gCJD V203I (100%). On the other hand the detection sensitivities of biomarkers were considerably lower: GSS (11%), FFI (0%), gCJD E200K (73%), and gCJD V203I (67%). Thus, RT-QUIC had a much higher detection sensitivity compared with testing for biomarkers, especially in patients with GSS and FFI. Conclusion/Significance: RT-QUIC assay is more sensitive than testing for biomarkers in gPrD patients. RT-QUIC method would thus be useful as a diagnostic tool when the patient or the patient\u27s family does not agree to genetic testing, or to confirm the diagnosis in the presence of a positive result for genetic testing

Successful Graft of HTLV‐I‐transformed Human T‐Cells (MT‐2) in Severe Combined Immunodeficiency Mice Treated with Anti‐asialo GM‐1 Antibody

To develop an experimental model of adult T‐cell leukemia/lymphoma in small animals, severe combined immunodeficiency (SCID) mice treated with anti‐asialo GM‐1 antibody were inoculated with MT‐2 cells, a cell line transformed by the human T‐cell leukemia virus (HTLV–I). Three mice injected with 4 × 107 cells subcutaneously or intramuscularly developed tumors at or near inoculation sites. Immunofluorescent antibody (IFA) staining for HTLV–I structural protein, p19, revealed the specific antigen in the cytoplasm of most cells from tumors and the DNA signals of HTLV–I proviral DNA were also positive in cellular DNA by polymerase chain reaction assay with HTLV–I tax gene primers, SK43/SK44. The MT–2 cells did not invade in mouse organs

Association of peripartum troponin I levels with left ventricular relaxation in women with hypertensive disorders of pregnancy

Objective Women with hypertensive disorders of pregnancy (HDP) show elevated risk of heart failure despite decreased circulating plasma volume compared with those with normotensive control pregnancies (NCP). This study was performed to better characterise the heart in women with HDP and determine whether high-sensitivity troponin I (hs-TnI) around childbirth predicts reduced left ventricular (LV) relaxation at 1 month postpartum. Methods Echocardiography was performed longitudinally during the first, second and third trimesters and immediately postpartum within 1 week and 1 month postpartum in 24 women with HDP, with simultaneous determination of blood variables in comparison with 51 women with NCP. Results Compared with NCP, HDP showed greater antepartum left atrial (LA) volume, LV mass and inferior vena cava (IVC) diameter, higher peripartum brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide and hs-TnI with the highest value immediately postpartum, and lower early diastolic mitral annular velocity (e') during pregnancy/postpartum. In analyses of data on HDP and NCP, hs-TnI at the third trimester as well as that immediately postpartum was negatively correlated with later e' at 1 month postpartum. The areas under the receiver operating characteristic curves were 0.82 and 0.81 for hs-TnI at the third trimester and immediately postpartum, respectively, in the prediction of reduced LV relaxation at 1 month postpartum. Conclusion Reduced LV diastolic function and decreased splanchnic blood reservoir may contribute to the increased third trimester IVC diameter and LA volume in women with HOP. The rise in hs-TnI around childbirth was associated with poor LV relaxation ability at 1 month postpartum

Relations of Strain Parameters to Wall Stress

Whether and how left ventricular (LV) strain and strain rate correlate with wall stress is not known. Furthermore, it is not determined whether strain or strain rate is less dependent on the afterload. In 41 healthy young adults, LV global peak strain and systolic peak strain rate in the longitudinal direction (LS and LSR, respectively) and circumferential direction (CS and CSR, respectively) were measured layer-specifically using speckle tracking echocardiography (STE) before and during a handgrip exercise. Among all the points before and during the exercise, all the STE parameters significantly correlated linearly with wall stress (LS: r = -0.53, p < 0.01, LSR: r = -0.28, p < 0.05, CS in the inner layer: r = -0.72, p < 0.01, CSR in the inner layer: r = -0.47, p < 0.01). Strain more strongly correlated with wall stress than strain rate (r = -0.53 for LS vs. r = -0.28 for LSR, p < 0.05; r = -0.72 for CS vs. r = -0.47 for CSR in the inner layer, p < 0.05), whereas the interobserver variability was similar between strain and strain rate (longitudinal 6.2 vs. 5.2 %, inner circumferential 4.8 vs. 4.7 %, mid-circumferential 7.9 vs. 6.9 %, outer circumferential 10.4 vs. 9.7 %), indicating that the differences in correlation coefficients reflect those in afterload dependency. It was thus concluded that LV strain and strain rate linearly and inversely correlated with wall stress in the longitudinal and circumferential directions, and strain more strongly depended on afterload than did strain rate. Myocardial shortening should be evaluated based on the relationships between these parameters and wall stress