Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study

Simultaneous Training for Children with Autism Spectrum Disorder and Their Parents with a Focus on Social Skills Enhancement

The objective of this study was to evaluate the effectiveness of simultaneous training for children with autism spectrum disorder (ASD) and their parents, with a focus on social skills enhancement (STSSE) by evaluating behavioral changes in children with ASD and changes in family functioning. STSSE was conducted on 17 children of elementary school age with ASD and their parents. Changes in scores on the social skills scale for education (SS-scale), the child behavior checklist, the Feetham Family Functioning Survey (FFFS), and the confidence degree questionnaire for families (CDQ) were used to assess the effectiveness of STSSE. Improvements were seen for “Communication Skills” on the children’s SS-scale (p = 0.029). Significant improvements were seen in the mothers’ FFFS scores for “The 4th factor: illness and worries” (p = 0.016) and in the median CDQ scores for one of 18 items after STSSE (p = 0.01). Although additional studies with larger sample sizes will be necessary before these findings are generalizable, the positive changes seen in both parents and children as a result of STSSE are promising

Effectiveness of a Parent Training Programme for Parents of Adolescents with Autism Spectrum Disorders: Aiming to Improve Daily Living Skills

Parent training (PT) has been well established in younger children with autism spectrum disorder (ASD) but is less well studied in adolescents. This study examined the effects of attempting PT to enhance the daily living skills (DLSs) of adolescents with ASD. Twenty-five parents of adolescents with ASD participated in either the immediate- or delayed-treatment control condition. Children’s DLSs were evaluated using the DLS domain of the Vineland Adaptive Behaviour Scales-II, and the achievement of the DLSs practised by the children at home was the subject of the evaluation. The DLS domain score showed no improvement in the treatment group compared to the control group. However, some parents in the treatment group reported that their children acquired the target DLSs and more sophisticated communication behaviours. In addition, one measure suggested that parents increased their praising behaviours. These changes may have been driven by the completion of the parent training. We discuss several aspects of developing parent-mediated interventions based on the current intervention situation and observed changes

High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype.

Regenerating islet-derived protein 3 alpha (REG3A) is a biomarker of lower gastrointestinal graft-versus-host disease (GVHD); however, the biological role of REG3A in the pathophysiology of GVHD is not understood. Here, we examined the association between a single nucleotide polymorphism in the REG3A gene, rs7588571, which is located upstream and within 2 kb of the REG3A gene, and transplant outcomes including the incidence of GVHD. The study population consisted of 126 adult Japanese patients who had undergone bone marrow transplantation from a HLA-matched sibling. There was no association between rs7588571 polymorphism and the incidence of acute GVHD. However, a significantly higher incidence of extensive chronic GVHD was observed in patients with the rs7588571 non-GG genotype than in those with the GG genotype (Odds ratio 2.6; 95% confidence interval, 1.1-6.0; P = 0.029). Semi-quantitative reverse transcription PCR demonstrated that the rs7588571 non-GG genotype exhibited a significantly lower REG3A mRNA expression level than the GG genotype (P = 0.032), and Western blot analysis demonstrated that the rs7588571 non-GG genotype exhibited a trend toward lower REG3A protein expression level than the GG genotype (P = 0.053). Since REG proteins have several activities that function to control intestinal microbiota, and since intestinal dysbiosis is in part responsible for the development of GVHD, our findings lead to the novel concept that REG3A could have some protective effect in the pathogenesis of GVHD through the regulation of gut microbiota

Expression level of <i>REG3A</i> in B-LCLs of each <i>REG3A</i> rs7588571 genotype.

<p><b>A. Semi-quantitative reverse transcription PCR for <i>REG3A</i></b>. Total RNA was extracted from three B-LCLs for each genotype and reverse transcribed. The cDNA equivalent to the same amount of total RNA was subjected to reverse trancription PCR. Panc-1, which is a pancreatic cancer cell line expressing <i>REG3A</i>, was used as a positive control. <i>GAPDH</i> was used as an internal control. <b>B. Comparison of <i>REG3A</i> expression level among rs7588571 genotypes</b>. The intensity of each PCR band was quantified, and expression levels of <i>REG3A</i> were normalized to <i>GAPDH</i> expression levels. The normalized expression level of <i>REG3A</i> in the GG genotype was used as a reference. The relative expression levels of <i>REG3A</i> were compared among the three rs7588571 genotypes using one-way ANOVA (left) and between the GG and non-GG genotypes using a t-test (right). Data of two independent experiments (mean ± S.E.M.) each performed in triplicate are shown. <b>C. Western blot for REG3A protein</b>. Lysate was extracted from three B-LCLs for each genotype that were used in Fig 1A. The same amount of lysate was applied in SDS-PAGE. Panc-1 was used as a positive control. The β-actin was used as a loading control. <b>D. Comparison of expression level of REG3A protein among rs7588571 genotypes</b>. The expression level of REG3A protein was quantified. The expression level of REG3A protein in the GG genotype was used as a reference. The relative expression levels of REG3A protein were compared among the three rs7588571 genotypes using one-way ANOVA (left) and between the GG and non-GG genotypes using a t-test (right). Data of two independent experiments (mean ± S.E.M.) are shown.</p

Univariate and multivariate analyses of risk factors for extensive chronic GVHD.

<p>Univariate and multivariate analyses of risk factors for extensive chronic GVHD.</p

Patient characteristics categorized by rs7588571 genotype.

<p>Patient characteristics categorized by rs7588571 genotype.</p