Multiplex PCRを用いた簡便で感度の高い溺死診断法の開発

For diagnosing death due to drowning, the method of acid digestion of diatoms is widely used to detect plankton in the organs of the corpse. However, the method is limited by its　being complex, hazardous, time-consuming, and insufficiently sensitive. We therefore, developed a novel simple method to diagnose death due to drowning, and determined the location of drowning by detecting genes of representative bacteria in the environment. To procure all the information in one step, the multiplex PCR method was designed. For the diagnosis of drowning, the genes of upper respiratory indigenous bacteria, Streptococcus salivarius and Streptococcus sanguinis were used as indicators. For detection of the location of drowning, Aeromonas hydrophila and Microcystis aeruginosa were used as indicators of freshwater, and Vibrio harveyi as an indicator of seawater. A set of primers was designed for multiplex PCR. to amplify all the bacterial genes simultaneously. Using this method, 47 cases of drowning were examined, and the causes and locations of death were diagnosed.博士（医学）・乙第1428号・平成31年3月15

口腔内所見を用いた新たな年齢推定法

In forensic science, age estimation is an important step in identifying unidentified cadavers. As teeth are resistant to environmental degradation for long periods of time, they are often used to estimate age. Although there have been many reports of age estimation based on dental morphology, these methods tend to be subjective and cannot be used i n the case of edentulous jaws. In the present study, we developed a new method of age estimation from dental parameters (number of upper teeth [UT], lower teeth [LT], and prostheses [NP]; tooth attrition [TA]; and occlusal area [OA]) and the mandibular angle (MA) measured at proposed an equation for calculating the age. The results show that the mean error of this method is similar to that of previous methods, and even demonstrated improved accuracy in subjects aged >60 years. We also proposed an equation for age estimation from only the MA, and showed that we can perform age estimation even in edentulous cases using this equation. Because our method is superior in its simplicity, objectivity, and applicability when compared with previous methods, we believe our method wll prove useful for age estimation in a wide variety of cases.博士（医学）・甲611号・平成26年3月17

High-throughput screening of cell death inducible short peptides from TNF-related apoptosis-inducing ligand sequence

AbstractTherapeutic peptides and small molecules, rationally designed to trigger cell death have attracted strong attention. Cell death inducible peptides were screened from amino acid sequence of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Using Fmoc solid phase synthesis, cellulose membrane-bound octameric peptide library of TRAIL scan was prepared and cell viability assay was directly performed on peptide disk with Jurkat cells. Six peptide sequences that could induce cell death were found. Peptide sequence with RNSCWSKD (TRAIL227–234) that exist in the zinc-binding site revealed high cell death inducible activity. Apoptotic cell death was observed when cells were treated with soluble synthesized peptide

保育現場における食育プログラムの効果を評価するための指標

　We systematically reviewed relevant published articles to identify the appropriate indices for evaluating the effectiveness of Food and Nutrition Education/Promotion targeted in early childhood care and education．We retrieved articles from the Igaku-chuo-zassi and CiNii databases．After reading the screened papers, we selected 12 original articles to complete the evidence table through in-depth analyses．In these studies, 5 methods were adopted to measure the indices for effect of nutrition education for preschool children: 1） impact for interest of food; 2） impact for consumption of food; 3） improving picky eating habits; 4） impact of eating behavior; 5） impact of parental eating consciousness and behavior．4 methods were adopted for evaluation items: 1） questionnaire survey for patrons; 2） questionnaire survey for nursery staffs; 3） observation record of children by nursery staffs and interviews of patrons; 4） consumption of food at home and preschool．Each method has its strengths and limitations．We concluded that the combination of subjective evaluation （questionnaires, observation records, and interviews） and objective evaluation（consumption of food） was the best option in many genuine settings of Food and Nutrition Education/Promotion programs because of their feasibility and acceptable validity．In future, it will be necessary to examine the sustained effect of nutrition programs

Ultrasound for Perioperative Lung Monitoring of Patients Undergoing Thoracic Surgery with One-Lung Ventilation

Background: The diagnostic efficacy of lung ultrasonography (LUS) has been widely investigated. However, the clinical value of LUS for perioperative monitoring has rarely been reported. The aim of this study was to evaluate the ability of LUS to assess lung aeration status after one-lung ventilation (OLV) using a validated scoring system. Methods: In this prospective observational study, patients undergoing elective video-assisted thoracic surgery (VATS) with OLV underwent a lung ultrasound examination just after induction of anesthesia and at the end of the surgery. After each lung ultrasound examination, a semiquantitative score, the LUS score, was calculated to assess lung aeration on the ventilated dependent side and the non-dependent side separately. The relationship between the LUS scores and various patient-related factors was also investigated. Results: Twenty-five patients were studied. All lung ultrasound examinations were successfully completed. LUS scores after OLV on the dependent side (median [IQR]: 2 [1–4]) increased significantly from baseline (1 [0–1.5], P < 0.001). Further, LUS scores on the non-dependent side (2 [1.5–3.5]) increased significantly from baseline (1 [0–1.5], P < 0.001). None of the factors analyzed was significantly correlated with LUS scores after OLV. Conclusion: LUS examination is possible after VATS with OLV on both sides of the thorax. Ultrasonography-measured lung aeration scores increased from baseline on both sides

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Peer reviewe

C9orf72由来のプロリン : アルギニンポリペプチドは細胞骨格とメカニカルストレス応答を制御する

Proline:arginine (PR) poly-dipeptides from the GGGGCC repeat expansion in C9orf72 have cytotoxicity and bind intermediate filaments (IFs). However, it remains unknown how PR poly-dipeptides affect cytoskeletal organization and focal adhesion (FA) formation. Here, we show that changes to the cytoskeleton and FA by PR poly-dipeptides result in the alteration of cell stiffness and mechanical stress response. PR poly-dipeptides increased the junctions and branches of the IF network and increased cell stiffness. They also changed the distribution of actin filaments and increased the size of FA and intracellular calcium concentration. PR poly-dipeptides or an inhibitor of IF organization prevented cell detachment. Furthermore, PR poly-dipeptides induced upregulation of mechanical stress response factors and led to a maladaptive response to cyclic stretch. These results suggest that the effects of PR poly-dipeptides on mechanical properties and mechanical stress response may serve as a pathogenesis of C9orf72-related neurodegeneration.博士（医学）・甲第846号・令和4年9月28日Copyright © 2022 Shiota, Nagata, Kikuchi, Nanaura, Matsubayashi, Nakanishi,Kobashigawa, Isozumi, Kiriyama, Nagayama, Sugie, Yamashiro and Mori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

The study of restrative planning and design on the Denton House, Doshisha Girls\u27 School

研究ノー

The Fab portion of immunoglobulin G contributes to its binding to Fcγ receptor III

Most cells active in the immune system express receptors for antibodies which mediate a variety of defensive mechanisms. These receptors interact with the Fc portion of the antibody and are therefore collectively called Fc receptors. Here, using high-speed atomic force microscopy, we observe interactions of human, humanized, and mouse/human-chimeric immunoglobulin G1 (IgG1) antibodies and their cognate Fc receptor, FcγRIIIa. Our results demonstrate that not only Fc but also Fab positively contributes to the interaction with the receptor. Furthermore, hydrogen/deuterium exchange mass spectrometric analysis reveals that the Fab portion of IgG1 is directly involved in its interaction with FcγRIIIa, in addition to the canonical Fc-mediated interaction. By targeting the previously unidentified receptor-interaction sites in IgG-Fab, our findings could inspire therapeutic antibody engineering

Near-Infrared Spectroscopy during the Verbal Fluency Task before and after Treatment with Image Exposure and SSRI Therapy in Patients with Obsessive-Compulsive Disorder

Drug therapy with selective serotonin reuptake inhibitors (SSRIs) has been used as a treatment for obsessive-compulsive disorder (OCD). In the present case report, exposure therapy was used in addition to escitalopram (20 mg) to treat a 28-year-old female patient with OCD for 6 months. Her obsessive-compulsive symptoms comprised thoughts of words such as rape, crematorium, neck hanging, unhappy, death, die, and kill and images such as a shelf of gods, a shrine, a Buddhist altar, the sun, the sky, and the faces of her parents, siblings, and relatives. As exposure therapy, she was asked to view the images associated with these symptoms three times a day along with drug therapy. With the combination of drug and exposure therapies, her obsessive-compulsive symptoms improved within 6 months, with no interference in her daily life. Multichannel near-infrared spectroscopy (NIRS) showed improvement of brain function in the temporal and frontal lobes after treatment. These results suggest that NIRS can be used as an indicator of brain function improvement in patients with OCD