Search Results (25)

In recent years, as gene therapy technology has rapidly developed, there has been growing concern that it could be misused by athletes as a means of doping. However, current testing methods for gene doping have a range of limitations and require further improvement. Furthermore, significant progress has been made in the fields of blood storage, next-generation sequencing (NGS), and LabDroid (experimental robots). Against this background, this study was implemented to develop a test method for gene doping using dried blood spot (DBS), NGS, and the LabDroid ”Maholo”. As a first step, recombinant adeno-associated virus containing the human erythropoietin gene (hEPO) was injected into mice to establish a gene doping model. Subsequently, DBS was created using whole blood. Maholo was used to extract DNA from the DBS and to create DNA libraries for NGS. NGS in combination with bioinformatic analysis clearly identified DNA fragments that provided definitive evidence of gene doping in the mouse model, which were absent in the control mouse. To the best of our knowledge, this is the first attempt to use a biological model of hEPO gene doping in conjunction with Maholo, NGS, and DBS. This method should facilitate the further development of gene doping tests. Full article

Background: Delirium is frequently observed in patients admitted to the intensive care unit, and is associated with mortality and morbidity. Although several studies have reported an association between polyunsaturated fatty acids (PUFAs) and cognitive disorders, the association between PUFA levels and development of delirium in patients with acute cardiovascular disease remains unknown. Objective: This study aimed to clarify the association between PUFA levels and development of delirium in the coronary intensive care unit (CICU). Methods: We enrolled 590 consecutive patients (mean age, 70 ± 14 years) admitted to the CICU of Juntendo University Hospital. Fasting serum PUFA levels were measured within 24 h of admission. Delta-5 desaturase activity was estimated as the ratio of arachidonic acid (AA) to dihomo-gamma-linolenic acid (DGLA). Furthermore, delirium was defined as patients having a delirium score of ≥4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was observed in 55 patients. DGLA levels were significantly lower, and delta-5 desaturase activity was significantly higher in patients with delirium than in those without delirium (both p < 0.001). Conversely, AA alone and omega-3 PUFAs did not differ between the groups. Additionally, DGLA and AA levels, but not omega-3 PUFA levels, were negatively associated; delta-5 desaturase activity was positively associated with the delirium score (both p < 0.001). The duration of delirium was significantly associated with DGLA and AA levels (p = 0.001 and p = 0.004, respectively). Moreover, multivariate analysis showed that decreased DGLA and increased delta-5 desaturase activity remained significant predictors of delirium. Conclusions: Low omega-6 PUFA levels and high delta-5 desaturase activity on admission were significantly associated with the development of delirium in the CICU, indicating that the evaluation of low omega-6 PUFA levels and related enzymes may identify patients at a high risk of developing delirium. Full article

Medical care for domestic dogs is now respected worldwide as being at a similar level to that of humans. We previously established a test method to determine whole mitochondrial DNA (mtDNA) using oral mucosal DNA that may be useful for medical care and welfare. However, the sample types tested in dogs are not limited to those obtained from the oral mucosa. Therefore, in the present study, we attempted to establish a test method to determine whole mtDNA sequences using feces, which represents the least invasive specimen. Two Japanese domestic dogs were used in the present study. DNA was extracted from approximately 100 mg of fresh feces from each dog, and PCRs were performed using four primer pairs that can amplify whole mtDNA. Following PCR, amplicons were pooled to create a DNA library using an experimental robot with an original program. Data were then acquired via NGS and data analysis was performed. The results showed that the whole mtDNA sequence of the two dogs was determined with high accuracy. Our results suggest that feces can be adapted for mitochondrial disease and individual identification testing and could serve as a useful testing method for the future medical care and welfare of domestic dogs. Full article

The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice. Full article

Poor posture in young adults and middle-aged people is associated with neck and back pain which are among the leading causes of disability worldwide. Training posture maintenance muscles and learning about ideal posture are important for improving poor posture. However, the effect of using both approaches simultaneously has not been verified, and it is unclear how long the effects persist after the intervention. Forty female university students were randomly and evenly assigned to four groups: physical function improvement training, posture learning, combination, and control groups. Four weeks of intervention training was conducted. Postural alignment parameters were obtained, including trunk anteroposterior inclination, pelvic anteroposterior inclination, and vertebral kyphosis angle. Physical function improvement training for improving crossed syndrome included two types of exercises: “wall-side squatting” and “wall-side stretching”. The posture learning intervention consisted of two types of interventions: “standing upright with their back against the wall” and “rolled towel”. A multiple comparison test was performed after analysis of covariance to evaluate the effect of each group’s postural change intervention on postural alignment. Only the combination group showed an effective improvement in all posture alignments. However, it was found that a week after the 4-week intervention, the subjects’ postures returned to their original state. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have a more potent glycated hemoglobin (HbA1c)-lowering effect than existing therapies and are widely used for treating type 2 diabetes mellitus (T2DM). Once-daily oral semaglutide is the world’s first oral GLP-1RA. This study aimed to provide real-world data on oral semaglutide in Japanese patients with T2DM and its effects on cardiometabolic parameters. This was a single-center retrospective observational study. We examined changes in HbA1c and body weight (BW) and the rate of achieving HbA1c < 7% after 6 months of oral semaglutide treatment in Japanese patients with T2DM. Furthermore, we examined differences in the efficacy of oral semaglutide with multiple patient backgrounds. A total of 88 patients were included in this study. Overall, the mean (standard error of the mean) HbA1c at 6 months decreased by −1.24% (0.20%) from baseline, and BW at 6 months (n = 85) also decreased by −1.44 kg (0.26 kg) from baseline. The percentage of patients who achieved HbA1c < 7% changed significantly from 14% at baseline to 48%. HbA1c decreased from baseline regardless of age, sex, body mass index, chronic kidney disease, or diabetes duration. Additionally, alanine aminotransferase, total cholesterol, triglyceride, and non-high-density lipoprotein cholesterol were significantly reduced from baseline. Oral semaglutide may be an effective option for the intensification of therapy in Japanese patients with T2DM who have inadequate glycemic control with existing therapy. It may also reduce BW and improve cardiometabolic parameters. Full article

Background: The role of healthcare professionals, including pharmacists, is changing. Lifelong learning and continuing professional development (CPD) are more critical than ever for both current and future pharmacists in the face of global health challenges and new technologies, services and therapies that are continually and rapidly introduced into their daily practice. Currently, Japanese pharmacists’ licences are not renewable, although most developed countries have a renewal system. Therefore, understanding Japanese pharmacists’ perceptions of CPD is the first step in reviewing undergraduate and postgraduate education. Methods: The target population was Japanese pharmacists, i.e., community pharmacy pharmacists and hospital pharmacists. The participants were administered a questionnaire with 18 items related to continuing professional development. Results: Our study found that regarding item “Q16 Do you think you need further education in your undergraduate education to continue your professional development?”, (a) the ability to identify one’s own problems and issues, (b) the ability to make plans to solve problems and issues, (c) the ability to carry out plans to solve problems and issues and (d) the ability to repeat steps of self-development, approximately 60% of pharmacists answered that these aspects were “necessary” or “quite necessary”. Conclusion: As part of universities’ responsibility for the lifelong education of pharmacists, it is necessary to systematically conduct teaching seminars or undergraduate education or postgraduate education on self-development while training pharmacists to meet the needs of citizens. Full article

This retrospective study aimed to investigate the survival rate of implants from 5 to 10 years after the placement of implant-supported fixed dental prostheses (ISFDPs) and the management of implant loss in the elderly population. Elderly patients (≥65 years old) who had been treated with ISFDPs and followed up with for at least 5 years between October 2009 and March 2020 were enrolled. Patient profiles and implant-related data were extracted. The survival rate of implants up to 5 years as well as the 10-year cumulative survival rate were evaluated. The management of implant loss and prosthetic interventions were also investigated. In total, 195 patients (mean age: 70.1 ± 4.5 years old) and 687 implants (287 ISFDPs) were assessed. The 5-year survival rate was 99.0% and the 10-year cumulative survival rate was 98.1%. Seven of the eleven implants lost were lost due to peri-implantitis. Only three implants in two patients were placed after the loss of the implants; most were restored using non-invasive procedures. Two patients underwent a conversion from ISFDPs to removable prostheses. This study showed that high survival rates were observed in an elderly population with ISFDPs and that non-invasive procedures were often applied after the loss of an implant. Full article

Background: Aluminium reduces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) survival in experimental settings. It is unknown whether adding an aluminium gauze to a mask reduces the SARS-CoV-2 RNA load in the mask and whether SARS-CoV-2 is detectable in the breath that permeates through such a mask in clinical settings. Methods: Patients admitted to Kishiwada City Hospital, Osaka, Japan, between July 2021 and September 2021 were enrolled in the study. Non-woven masks comprising filters with 99% viral filtration efficacy and aluminium and cotton gauzes attached to plastic collection cases were developed. All participants wore the experimental mask models for three hours. Results: Twenty-nine patients who wore the final model masks were analysed in this study. The Ct values of the nucleocapsid gene and envelope gene of SARS-CoV-2 were significantly higher in the aluminium gauze than in the cotton gauze. SARS-CoV-2 RNA was detected in the masks of 8 out of 12 vaccinated patients (66.7%). Although breath condensates were collected behind both aluminium and cotton gauzes, SARS-CoV-2 RNA was not detected in these condensates. Conclusions: Our study indicated that non-woven masks with an aluminium gauze may obstruct SARS-CoV-2 transmission in clinical settings better than non-woven masks with cotton gauzes. Full article

To achieve curative resection for pancreatic cancer during pancreaticoduodenectomy (PD), extensive portal vein (PV) resection, including porto-mesenterico-splenic confluence (PMSC), may sometimes be necessary if the tumor is close to the portal venous system. Recently, this extended resection has been widely accepted in high-volume centers for pancreatic resection due to its favorable outcomes compared with non-operative treatment. However, in patients with long-term survival, sinistral portal hypertension (SPH) occurs as a late-onset postoperative complication. These patients present gastrointestinal varices due to congested venous flow from the spleen, which may cause critical variceal bleeding. Since the prognosis of patients with pancreatic cancer has improved, owing to the development of chemotherapy and surgical techniques, SPH is no longer a negligible matter in the field of pancreatic cancer surgery. This review clarifies the pathogenesis and frequency of SPH after PD through PMSC resection and discusses its prediction and prevention. Full article

The objective of this study was to investigate a bone graft substitute containing carbonate apatite (CO₃Ap) to analyze bone replacement and the state of bone formation in vitro and in vivo compared with autogenous bone (AB) or control. An osteoclast precursor cell line was cultured with AB or CO₃Ap, and morphological analysis using scanning electron microscopy and a tartrate-resistant acid phosphatase activity assay were performed. The right maxillary first and second molars of Wistar rats were extracted and compensated by AB or CO₃Ap granules. Following implantation, the bone formation state was evaluated after 3, 5, 7, 14, and 28 days of surgery by micro-computed tomography and immunohistostaining. The osteoclast-like cell morphology was typical with many cell protrusions in the AB and CO₃Ap groups. Additionally, the number of osteoclast-like cells formed in the culture increased in each group; however, there was no significant difference between the AB and CO₃Ap groups. Five days after tooth extraction, osteoclasts were observed near CO₃Ap. The bone thickness in the CO₃Ap group was significantly increased than that in the control group and the bone formation in the CO₃Ap group increased by the same level as that in the AB group. CO₃Ap is gradually absorbed by osteoclasts in the extraction socket and is easily replaced by alveolar bone. The process of bone replacement by osteoclasts is similar to that of autologous bone. By observing the process of bone replacement in more detail, it may be possible to gain a better understanding of the bone formation and control the amount of bone after surgery. Full article

The aim of this pilot study was to evaluate the accuracy of a newly developed dynamic navigation system and to compare the accuracy between flapless and open-flap surgery, and between surgeons. The subjects were patients who were scheduled to receive implants of the same size using the newly developed dynamic navigation system. The study’s procedures included cone beam computed tomography (CBCT) filming with fiducials, virtual planning of implant placement and the use of motion tracking technology for calibration and practical implant placement. The accuracy was evaluated using preoperative (virtual implant) and postoperative (actual implant) CBCT images based on angular, apical, coronal and vertical deviations. The differences of deviations between flapless and open-flap surgery, and between two surgeons, were statistically compared. In total, 66 implants were placed in 39 patients. The median and interquartile range of angular, apical, coronal and vertical deviations were 3.07° (2.52–3.54°), 0.96 mm (0.75–1.42 mm), 0.76 mm (0.57–1.37 mm) and 0.71 mm (0.61–0.88 mm), respectively. These deviations were similar to those found in previous studies. Flapless surgery resulted in a more accurate placement with respect to apical and coronal deviations, and the differences between the two surgeons were limited. The newly developed dynamic navigation system is considered to be eligible for clinical use. Full article

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice. Full article

In this paper, we present a Deep Learning-based system for the support of information triaging on Twitter during emergency situations, such as disasters, or other influential events, such as political elections. The system is based on the assumption that a different type of information is required right after the event and some time after the event occurs. In a preliminary study, we analyze the language behavior of Twitter users during two kinds of influential events, namely, natural disasters and political elections. In the study, we analyze the credibility of information included by users in tweets in the above-mentioned situations, by classifying the information into two kinds: Primary Information (first-hand reports) and Secondary Information (second-hand reports, retweets, etc.). We also perform sentiment analysis of the data to check user attitudes toward the occurring events. Next, we present the structure of the system and compare a number of classifiers, including the proposed one based on Convolutional Neural Networks. Finally, we validate the system by performing an in-depth analysis of information obtained after a number of additional events, including an eruption of a Japanese volcano Ontake on 27 September 2014, as well as heavy rains and typhoons that occurred in 2020. We confirm that the methods works sufficiently well even when trained on data from nearly 10 years ago, which strongly suggests that the model is well-generalized and sufficiently grasps important aspects of each type of classified information. Full article