Genetic Association Analysis of ITGB3 Polymorphisms with Age at Onset of Schizophrenia

Schizophrenia (SCZ) is a debilitating disorder with a prevalence of approximately 1 % worldwide. SCZ is known to have a high degree of genetic and clinical heterogeneity and is a major health problem worldwide. The integrin-β 3 subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric disorders. We therefore hypothesized that ITGB3 gene polymorphisms might also play a role in SCZ and age at onset (AAO) of SCZ. We investigated the genetic associations of 23 single-nucleotide polymorphisms (SNPs) of the ITGB3 gene with AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear regression analysis and meta-analysis. We observed four ITGB3-SNPs associated with AAO in SCZ in a non-Genetic Association Information Network (GAIN) sample (p?<?10^?3). Three of these four SNPs were replicated in the GAIN sample. The SNP rs16941771 was most significantly associated with AAO (p?=?7.47?×?10^?5). Meta-analysis showed that 6 of 23 SNPs were associated with AAO. The haplotype analysis also supports the association of ITGB3 with AAO. Three disease-associated SNPs were located at species-conserved regions, indicating functional importance. This is the first report which shows that ITGB3 variants are associated with AAO in SCZ, providing direct evidence of the use of AAO as an intermediate phenotype to dissect the complex genetics of SCZ.     

Perinatal infection and hypoxic-ischemic encephalopathy: a pilot study

Recent studies suggest a synergic effect of infection and hypoxia-ischemia in the causation of perinatal brain damage. We conducted a prospective pilot study on the presence of infection in hypoxic-ischemic encephalopathy (HIE), focusing on neurotropic viruses. Sixteen newborns with HIE were included in the study. There were no confirmed cases of viral infection. There was a case of bacterial early onset sepsis and four cases of suspected sepsis due to clinical and/or analytical signs, but with negative cultures. Our results do not support universal screening for viral infection in cases of HIE.     

Psychometric properties of the EQ-5D-5L in patients with hip or knee osteoarthritis: reliability,validity and responsiveness

Purpose

To study the psychometric properties, including reliability, validity and responsiveness, of the Spanish EQ-5D-5L questionnaire for patients with hip or knee osteoarthritis (OA).

Methods

We included 758 patients with hip or knee OA who completed the EQ-5D-5L and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, of whom 644 also did 6 months later. The EQ-5D-5L contains five questions from which a utility index is derived. The WOMAC covers three dimensions: pain, stiffness and physical function. Floor and ceiling effects were calculated. Reliability was assessed using Cronbach’s alpha. Convergent validity was tested using the Spearman correlation coefficient between EQ-5D-5L and WOMAC. We examined known-groups validity by comparing the EQ-5D-5L between subgroups defined by WOMAC scores using ANOVA or the Kruskal–Wallis test. Effect sizes were calculated to assess responsiveness, and minimal clinically important difference (MCID) was estimated.

Results

The EQ-5D-5L showed minimal floor and ceiling effects (<?3%). Cronbach’s alpha was 0.86. The EQ-5D-5L index was strongly correlated with WOMAC pain and function scores (??0.688 and ??0.782). Patients with higher WOMAC scores had significantly (p?<?0.0001) lower EQ-5D-5L index. The 20.19% had hip or knee replacement during the follow-up. Effect sizes were small among non-surgical patients, but >?0.80 among “improved” surgical patients, being the MCID for improvement 0.32 points.

Conclusions

The results support the reliability, validity and responsiveness of the EQ-5D-5L, overcoming the limitations of the EQ-5D-3L in these patients. Therefore, the EQ-5D-5L could be very useful as an outcome measure, at least in patients with hip or knee OA.

     

Clinical and histological evaluation of immediate-loaded posterior implants in nonhuman primates

PURPOSE: To evaluate a square-thread design implant and compare the bone-implant contact percentage between immediate-loaded and nonloaded implants (controls) in nonhuman primates. MATERIALS: Five nonhuman primates each received 3 implants, with a total of 5 control implants and 10 immediate-loaded implants in posterior regions of the mouth. Ninety days after surgery (and function was appropriate), block sections of the implants were removed and sectioned in 200-mum thick pieces. The block sections were stained with modified Masson for evaluation of the bone-implant contact percentage. RESULTS: One of the immediate-loaded implants failed. The bone-implant contact percentage of control implants ranged from 50.34% to 64.13% and averaged 56.3%. The bone-implant contact percentage of immediate-loaded implants ranged from 43.23% to 75.72%, with an average of 62.4%. Two implants had lower bone-implant contact percentage than the others, and when these are not included in the evaluation, the bone-implant contact percentage average increased to 67.6%. CONCLUSIONS: Immediate-loaded implants in the nonhuman primates often have a higher bone-implant contact percentage at 90 days than unloaded implants. The bone remodeling is different for loaded implant-bone interfaces than for unloaded conditions. However, 1 immediate-loaded implant failed, and 2 implants had lower bone-implant contact percentage than controls. Therefore, although there are benefits of immediate loading, there appear to also be some risks.     

Testing general self‐efficacy,perceived competence,resilience, and stress among nursing students: An integrator evaluation

The purpose of this study was to develop a predictive model for perceived competence and to obtain an integrator evaluation of the nursing curriculum with measures of nursing self‐efficacy, general self‐efficacy, resilience, and stress among nursing students. A correlational study with nursing students (N = 265) from the degree in nursing was conducted. A factor analysis was used to test the construct validity of nursing self‐efficacy and perceived competence. The correlational and discriminant analyses evaluated the factors in the four academic levels of the degree (2016–2017) to identify the variables involved in the classification of the students in each level. The results of exploratory and confirmatory factor analyses of nursing self‐efficacy and perceived competence revealed a statistically significant good fit and consistency. Nursing self‐efficacy, general self‐efficacy, resilience, and year of the degree course predicted 34% of perceived competence scores. The discriminant function of nursing self‐efficacy, perceived competence, and resilience classified 76% of participants in the first and last years of the degree. Nursing self‐efficacy, perceived competence, and resilience increased with academic level. They help chart nursing students' progress through the curriculum.     

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and non-hematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.