ミリ秒精度での時間処理の不安定さは，自閉症スペクトラム障害における感覚運動障害の重要な特徴である : 同期指タッピング課題を用いた解析

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(保健学)Doctor of Philosophy in Health Sciencedoctora

Effects of DNA degradation and genotype imputation on high-density SNP microarray in pairwise kinship analysis

High-density single nucleotide polymorphisms (SNPs) can detect distant relatives even in the context of pairwise kinship analysis. Although DNA microarrays conveniently generate genome-wide SNP data, they require large quantities of high-quality DNA. Genotyping data obtained from low-quantity and low-quality samples are likely unreliable owing to the incidence of no-called or mistyped SNPs. In this study, we examined the effects of insufficient sample densities and sample degradation on the efficacy of kinship analysis. While low DNA amounts had a minor effect, DNA degradation led to a significant increase in no-call rates and error rates. Posterior probabilities of kinship determination, calculated using the index of chromosomal sharing, were markedly lower in proportion to the no-call rates and error rates. We also investigated the effect of genotype imputation to complement the no-called genome data utilizing SNPs reference panels. We found that the posterior probability of the relative-assumed person increased with genotype complementation in case of mild degradation, even with mistyped genotypes. Therefore, DNA microarray with imputation is a promising method for analyzing forensic DNA samples taken from situations where DNA quantity and quality may be compromised, such as disaster victim identification using pairwise kinship analysis

Anti-Siglec-15 antibody suppresses bone resorption by inhibiting osteoclast multinucleation without attenuating bone formation

Anti-resorptive drugs are widely used for the treatment of osteoporosis, but excessive inhibition of osteoclastogenesis can suppress bone turnover and cause the deterioration of bone quality. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is a transmembrane protein expressed on osteoclast precursor cells and mature osteoclasts. Siglec-15 regulates proteins containing immunoreceptor tyrosine-based activation motif (ITAM) domains, which then induce nuclear factor of activated T-cells 1 (NFATc1), a master transcription factor of osteoclast differentiation. Anti-Siglec-15 antibody modulates ITAM signaling in osteoclast precursors and inhibits the maturation of osteoclasts in vitro. However, in situ pharmacological effects, particularly during postmenopausal osteoporosis, remain unclear. Here, we demonstrated that anti-Siglec-15 antibody treatment protected against ovariectomy-induced bone loss by specifically inhibiting the generation of multinucleated osteoclasts in vivo. Moreover, treatment with anti-Siglec-15 antibody maintained bone formation to a greater extent than with risedronate, the first-line treatment for osteoporosis. Intravital imaging revealed that anti-Siglec-15 antibody treatment did not cause a reduction in osteoclast motility, whereas osteoclast motility declined following risedronate treatment. We evaluated osteoclast activity using a pH-sensing probe and found that the bone resorptive ability of osteoclasts was lower following anti-Siglec-15 antibody treatment compared to after risedronate treatment. Our findings suggest that anti-Siglec-15 treatment may have potential as an anti-resorptive therapy for osteoporosis, which substantially inhibits the activity of osteoclasts while maintaining physiological bone coupling.Tsukazaki H., Kikuta J., Ao T., et al. Anti-Siglec-15 antibody suppresses bone resorption by inhibiting osteoclast multinucleation without attenuating bone formation. Bone 152, 116095 (2021); https://doi.org/10.1016/j.bone.2021.116095

Gastroesophageal reflux disease is a risk factor for sputum production in the general population: the Nagahama study

Background: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners. Methods: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined. Results: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production. Conclusions: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production

The importance of central airway dilatation in patients with bronchiolitis obliterans

Background: Bronchiolitis obliterans (BO) is a clinical syndrome characterised by progressive small airway obstruction, causing significant morbidity and mortality. Central airway dilatation is one of its radiological characteristics, but little is known about the clinical and pathological associations between airway dilatation and BO. Methods: This retrospective study consecutively included patients who underwent lung transplantation due to BO at Kyoto University Hospital from 2009 to 2019. Demographic and histopathological findings of the resected lungs were compared between patients with and without airway dilatation measured by chest computed tomography (CT) at registration for lung transplantation. Results: Of a total of 38 included patients (median age, 30 years), 34 (89%) had a history of hematopoietic stem-cell transplantation, and 22 (58%) had airway dilatation based on CT. Patients with airway dilatation had a higher frequency of Pseudomonas aeruginosa isolation with greater residual volume than those without airway dilatation. Quantitative CT analysis revealed an increase in lung volume to predictive total lung capacity and a percentage of low attenuation volume <-950 HU at inspiration in association with the extent of airway dilatation. Airway dilatation on CT was associated with an increased number of bronchioles with concentric narrowing of the lumen and thickening of the subepithelium of the walls on histology. Conclusions: In patients with BO, airway dilatation may reflect increased residual volume or air trapping and pathological extent of obstructive bronchioles, accompanied by a risk of Pseudomonas aeruginosa isolation. More attention should be paid to the development of airway dilatation in the management of BO

Association between discontinuation of benzodiazepine receptor agonists and post-operative delirium among inpatients with liaison intervention : A retrospective cohort study.

Background:Several studies have investigated the association between benzodiazepine receptor agonist (BZDRA) use during the perioperative period and an elevated incidence of delirium. However, no study has focused on the time course of BZDRA use, including continuation, discontinuation, initiation, and no use. This study aimed to examine the influence of the time course of BZDRA use on post-operative delirium.Methods:This retrospective cohort study was conducted by reviewing medical records. We included patients who were scheduled for surgery under general anesthesia and had been referred to a liaison psychiatrist for pre-operative psychiatric assessment. The patients were classified into four groups based on the pre- and post-operative time course of oral BZDRA use, as follows: continuation, discontinuation, initiation, and no use (never used). The primary outcome was the prevalence of post-operative delirium in non-intensive care unit settings. We also performed stratified analyses according to age, the presence of cognitive impairment, the presence of delirium history, and antipsychotic drug use on admission.Results:Among 250 patients, 78 (31%) developed post-operative delirium. The Discontinuation group had a higher rate of delirium (49%, 24/49) than the other groups (Continuation [14%, 4/29]; Initiation [38%, 3/8], Never used [29%, 47/164], p = 0.008).Conclusions:Abrupt discontinuation of BZDRAs during the perioperative period may be a risk factor for post-operative delirium and should therefore be avoided

The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia

Background : The safety and usefulness of the SILS-TAPP (transabdominal preperitoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. Patients and methods : 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients ; TAPP, 20 patients ; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. Results : There was no difference in the patients’ characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. Conclusions : The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia

Trends in health outcomes for family caregivers of hip‐fractured elders during the first 12 months after discharge

Aim.  This article reports on trends in health outcomes for family caregivers of hip‐fractured patients and the effects of social support on these outcomes. Background.  Little is known about the impact of caregiving on the health outcomes of family caregivers of patients with hip fracture. Method.  For this prospective, correlational study, data were collected from 135 family caregivers of hip‐fractured elders (2001–2005). Data on health‐related quality of life and social support were collected from family caregivers at 1, 3, 6 and 12 months after discharge of the older hip‐fractured patient. Findings.  During the 12 months after the patients’ discharge, family caregivers’ scores improved significantly in role performance‐related scales, including bodily pain, social function, role limitations due to emotional problems and role limitations due to physical problems. However, caregivers’ scores for general health and mental health were significantly lower at 12 months [59·91 ( sd  = 24·54) and 65·91 ( sd  = 14·36) respectively] than at 1 month after discharge [64·35 ( sd  = 23·29) and 67·94 ( sd  = 18·47) respectively]. The trends for most subscale scores for health‐related quality of life were positively related to perceived availability of social support. Conclusions.  Caring for a hip‐fractured older family member over a sustained period may enhance family caregivers’ role performance, but have a negative impact on their perceived general health and mental health. These results suggest that home care nurses should develop interventions early after discharge to assess and improve family caregivers’ health perception, mental health and social support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90349/1/j.1365-2648.2011.05778.x.pd

ヒダイショウセイ カンコウヘン ト シンフゼン オ トモナウ セイジン コウツウセイ インノウ スイシュ ニ タイシテ ツリアゲシキ LPECホウ オ シコウシタ 1レイ

We report Laparoscopic percutaneous extraperitoneal closure（LPEC）by lifting abdominal wall is safe and feasible for an adult communicating hydrocele with decompensated cirrhosis and heart failure. The patient was a７1-year-old man with communicating hydrocele. He has been treated for several years for alcoholic liver cirrhosis, diabetes and sick sinus syndrome. Preoperative laboratory examination showed a decrease in platelet count, liver dysfunction, hypoxemia, restrictive impairment and heart failure. Enhanced pelvic computed tomography scan revealed a continuous low density area in the right inguinal region from the scrotum. Outside of the right inferior epigastric artery and vein, the abdominal cavity and scrotum were communicated. Thus, right communicating hydrocele was diagnosed. To avoid complications due to pneumoperitoneum, LPEC with lifting abdominal wall was performed. There were no intra-and post-operative complications, and there has been no recurrence

イガン ニ タイスル da Vinci シュジュツ ノ ケイケン

The da Vinci Surgical System is a telerobotic system consisting of４components, including the Insite vision system with a true３‐dimensional endoscope providing a high-resolution binocular view of the surgical field, and the Endo Wrist instrument system, which is capable of７degrees of freedom and２degrees of axial rotation to replicate human wrist-like movements. Distal gastrectomy and D１＋lymphnode dissection was performed in a７３-year-old man with cT１bN０N０StageIA gastric cancer. Preoperative abdominal CT findings were showed that celiac artery branching patterns was Adachi VI type２６groups. The operating time was４３３minutes, and the blood loss was２８４g. The da Vinci Surgical System has useful advantages over conventional Laproscopic Assisted gastrectomy（LAG）surgery concerning the precise lymphnodes dissection. With further innovations in the future, the da Vinci Surgical System has the potential to facilitate technically difficult surgery employing conventional LAG techniques