Genetic Evidence for Single-Strand Lesions Initiating Nbs1-Dependent Homologous Recombination in Diversification of Ig V in Chicken B Lymphocytes

Homologous recombination (HR) is initiated by DNA double-strand breaks (DSB). However, it remains unclear whether single-strand lesions also initiate HR in genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig) V genes through HR (Ig gene conversion) and non-templated hypermutation. Both types of Ig V diversification are initiated by AID-dependent abasic-site formation. Abasic sites stall replication, resulting in the formation of single-stranded gaps. These gaps can be filled by error-prone DNA polymerases, resulting in hypermutation. However, it is unclear whether these single-strand gaps can also initiate Ig gene conversion without being first converted to DSBs. The Mre11-Rad50-Nbs1 (MRN) complex, which produces 3′ single-strand overhangs, promotes the initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a truncated form of Nbs1 (Nbs1p70) exhibits defective HR-dependent DSB repair, and a significant reduction in the rate—though not the fidelity—of Ig gene conversion. Interestingly, this defective gene conversion was restored to wild type levels by overproduction of Escherichia coli SbcB, a 3′ to 5′ single-strand–specific exonuclease, without affecting DSB repair. Conversely, overexpression of chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10-fold, with no effect on Ig gene conversion. These results suggest that Ig gene conversion may be initiated by single-strand gaps rather than by DSBs, and, like SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation may share a common substrate—single-stranded gaps. Genetic analysis of the two types of Ig V diversification in DT40 provides a unique opportunity to gain insight into the molecular mechanisms underlying the filling of gaps that arise as a consequence of replication blocks at abasic sites, by HR and error-prone polymerases

Premature oral pre-shaping for feeding in elderly population with risk of aspiration pneumonia.

The aim of this study was to determine the abnormal hand and mouth behavior before actual swallowing for eating in elderly people with high risk of aspiration pneumonia. Ten elderly people with a diagnosis of aspiration pneumonia (EAP), 15 healthy elderly (HE) people, and 21 young adults (YA) were enrolled. The feeding time and the timing of the maximum distance between the upper and lower lips were extracted using a motion analyzer during self-feeding and assisted-feeding. The results showed that feeding time in EAP was significantly longer than that for the other groups in self- and assisted-feeding. In self-feeding, the timing of mouth-preparation in the EAP group was significantly earlier than that in the other groups; conversely, in assisted-feeding, the timing in EAP was significantly delayed. Our results indicate that abnormal preparation of mouth-shape and movement time of hand before actual swallowing in both self- and assisted-feeding may exist in elderly people with previous experience of aspiration pneumonia

Reliability and Validation of the Japanese Version of the Patient Empowerment Scale

Empowerment scales for inpatients have been developed worldwide, but their validity and reliability have not been adequately tested and applied to the health promotion and care among older adults during hospitalization. In this study, the Patient Empowerment Scale developed by Faulkner was translated into Japanese, and Japanese patients were surveyed to test its clinical applicability. To test its applicability, 151 patients in rehabilitation wards were surveyed in four municipalities. After considering ceiling/floor effects and validating the structure, the Patient Empowerment Scale—Japanese comprised 37 items and six factors: subject–staff interaction, environmental adjustment through collaboration, necessary information gathering and problem awareness, proactive behavioral practices, self-disclosure, and self-management of activities. Criteria-related validity assessment confirmed the scale’s correlation with the Health Locus of Control Scale, General Self-Efficacy Scale, 13-item Sense of Coherence Scale, Rosenberg Self-Esteem Scale, and Philadelphia Geriatric Center Morale Scale. Regarding internal consistency, the Cronbach’s alpha was 0.93 for all 37 items. The Cronbach’s alphas for the six factors were 0.93, 0.91, 0.92, 0.92, 0.91, and 0.75, respectively. In our test/re-test of reliability, Spearman’s rank correlation coefficient between the first and second total scores was ρ = 0.96, p < 0.01. These results confirm the scale’s validity and reliability, and its applicability to older hospitalized patients

Relationship between Empowerment and Functioning and Disability in Older Japanese Patients: A Covariance Structure Analysis

In the present study, 151 Japanese older adults aged over 65 years and admitted to recovery-phase rehabilitation facilities were enrolled to investigate the relationship between empowerment and contextual factors, functioning and disability, with structural equation modeling (SEM). The analysis included 151 patients aged 81.75 ± 7.15 years, including 54 males (35.76%) and 97 females (64.24%). The results of the SEM analysis showed that role presence (β = 0.45, p p = 0.02) significantly impacted empowerment. In addition, the results showed that patient empowerment positively impacted physical activity (β = 0.25, p p < 0.01). Furthermore, the goodness-of-fit of the model hypothesized in this study was shown to have explanatory power. This study showed that empowerment contributed to the prevention of physical inactivity and confinement among Japanese older patients. In other words, the study provided evidence for the importance of empowerment-based program planning in the practice of person-centered care aimed at promoting the health and discharge of older patients in Japan

Long-term outcomes of delayed clozapine initiation in treatment-resistant schizophrenia: a multicenter retrospective cohort study

Abstract Background Clozapine is the only antipsychotic medication with proven efficacy against treatment-resistant schizophrenia. This multicenter retrospective cohort study aimed to evaluate the impact of a delay in clozapine initiation on long-term outcomes. Methods Patients who initiated clozapine treatment between July 2009 and December 2018 were included in this study. According to the length of time from the diagnosis of schizophrenia to clozapine initiation, the patients were categorized into one of three groups: early (≤ 9 years), intermediate (10–19 years), and late (≥ 20 years) initiation. The endpoints were psychiatric rehospitalization and all-cause clozapine discontinuation within 3 years. Hazard ratios (HR) and 95% confidence interval (CI) were estimated using the Fine and Gray method or the Cox proportional hazards model. Results The incidence rates of rehospitalization within three years, according to the cumulative incidence function, were 32.3% for early, 29.7% for intermediate, and 62.2% for late initiation, respectively. Late initiation had a significantly higher risk of psychiatric rehospitalization than early initiation (HR, 2.94; 95% CI, 1.01– 8.55; P = 0.016 by the Gray's test). The risk of psychiatric rehospitalization was not significantly different between the early and intermediate initiation groups. The incidence rate of all-cause clozapine discontinuation within three years using the Kaplan–Meier method was 13.0% for early, 10.6% for intermediate, and 20.1% for late initiation. The risk of all-cause clozapine discontinuation was not significantly among the groups. The late initiation group had more patients discontinuing because of death due to physical diseases than the other groups. Conclusions The study suggests that clozapine should be initiated promptly in patients with treatment-resistant schizophrenia to prevent psychiatric rehospitalization during long-term treatment. Further prospective studies with appropriate consideration of confounding factors and large sample sizes are needed to strengthen the evidence