Search

Dental caries and periodontal disease are typical oral diseases frequently observed in patients with renal diseases. Tooth loss is an outcome of dental caries and periodontal disease, and the number of existing teeth is an indicator of oral health status. However, the association between the number of existing teeth and end-stage kidney disease (ESKD) has not been investigated in detail. This study aimed to investigate the association between oral health status, expressed by the number of existing teeth, and ESKD. We analyzed data from the second survey of the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists, a cohort study conducted among members of the Japan Dental Association. From August 2016 to July 2017, self-administered questionnaires were mailed to 16,128 male dentists and 8,722 responded. Among them, 7,479 men with complete data on age, number of existing teeth, and ESKD were included in the analysis. Multivariate logistic regression analysis was conducted, with ESKD as the dependent variable and the number of existing teeth (≥23 teeth and

The nucleic acids found in food play a crucial role in maintaining various bodily functions. This study investigated the potential anticancer effects of dietary nucleic acids, an area that is still not fully understood. By utilizing an in vivo mouse model and an in vitro cell model, we discovered an anti-proliferative impact of RNA in both systems. DNA exhibited anti-proliferative effects in the mouse model, while this phenomenon wasn't observed in the in vitro cell model using Ehrlich ascites tumor (EAT) cells. Conversely, DNA hydrolysate demonstrated distinct anti-proliferative effects in EAT cells, suggesting that nucleotides or nucleosides generated during nucleic acid digestion act as active constituents. Furthermore, we examined various nucleosides and two sodium-independent equilibrative nucleoside transporter inhibitors (ENTs), identifying guanosine and 2'-deoxyguanosine as pivotal in the anti-proliferative effect. We also found that the anti-proliferation activity with both nucleosides was suppressed by the treatment of dipyridamole, a non-selective inhibitor for ENT1 and ENT2, but not nitrobenzylthioinosine, a low inhibitor for ENT2. The uptake of these compounds into cells is likely facilitated by ENT2. These nucleotides impeded the progression of cancer cells from the G1 phase to the S phase in the cell cycle. Another significant finding is the increased expression of CCAAT/enhancer-binding protein (C/EBPβ) induced by guanosine and 2'-deoxyguanosine. Furthermore, immunostaining revealed that C/EBPβ diffuses into the nucleus, indicating its presence. This suggests that guanosine or 2-deoxyguanosine induces G1 arrest in cancer cells via the activation of C/EBPβ. Encouraged by these promising results, guanosine and 2'-deoxyguanosine show potential applications in cancer prevention.

AimThis study aimed to determine whether excessive maternal weight gain during pregnancy was associated with a higher risk of prolonged labor.MethodsWe analyzed the data regarding maternal weight gain during pregnancy for the participants of Japan Environment and Children's Study (JECS), which is an ongoing nationwide prospective birth cohort study in Japan. After excluding participants with multiple pregnancies, with deliveries before 37 or beyond 42 weeks of gestation, or who had undergone cesarean section, 71,154 (nulliparous, n = 28,442) Japanese women were included. Prolonged labor was defined by a cutoff ranking at the 95th percentile and consequently defined as labor duration exceeding 12.7 h in multiparous women and exceeding 23.2 h in nulliparous women. These classifications were made according to labor curves established by the Japanese Society of Obstetrics and Gynecology Perinatal Committee developed in June 2021. Considering that no studies have conducted an investigation based on this new guideline, we analyzed the association between excessive maternal weight gain during pregnancy and prolonged labor by parity.ResultsThe overall incidence of prolonged labor was 10.2% (2,907/28,442) in nulliparous women and 6.1% (2,597/42,712) in multiparous women. Multivariable analysis indicated that excessive maternal weight gain was significantly associated with prolonged labor in nulliparous (adjusted odds ratio, 1.21; 95% confidence interval, 1.10-1.32) and multiparous women (adjusted odds ratio, 1.15; 95% confidence interval, 1.05-1.27). Kaplan-Meier survival analysis showed that as labor progressed, the percentage of women who had not yet delivered was higher among those with excessive maternal weight gain than among those with normal maternal weight gain in both the nulliparous (median labor duration 12.9 h vs 12.2 h, pConclusionExcessive maternal weight gain was significantly associated with prolonged labor in Japanese women.

In this study, we attempted to improve brain-computer interface (BCI) systems by means of auditory stream segregation in which alternately presented tones are perceived as sequences of various different tones (streams). A 3-class BCI using three tone sequences, which were perceived as three different tone streams, was investigated and evaluated. Each presented musical tone was generated by a software synthesizer. Eleven subjects took part in the experiment. Stimuli were presented to each user's right ear. Subjects were requested to attend to one of three streams and to count the number of target stimuli in the attended stream. In addition, 64-channel electroencephalogram (EEG) and two-channel electrooculogram (EOG) signals were recorded from participants with a sampling frequency of 1000 Hz. The measured EEG data were classified based on Riemannian geometry to detect the object of the subject's selective attention. P300 activity was elicited by the target stimuli in the segregated tone streams. In five out of eleven subjects, P300 activity was elicited only by the target stimuli included in the attended stream. In a 10-fold cross validation test, a classification accuracy over 80% for five subjects and over 75% for nine subjects was achieved. For subjects whose accuracy was lower than 75%, either the P300 was also elicited for nonattended streams or the amplitude of P300 was small. It was concluded that the number of selected BCI systems based on auditory stream segregation can be increased to three classes, and these classes can be detected by a single ear without the aid of any visual modality.

BackgroundAltered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN.MethodsThe tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated.ResultsIn total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis.ConclusionsThe present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.

BackgroundAcute kidney injury (AKI) is a critical complication of immune checkpoint inhibitor therapy. Since the etiology of AKI in patients undergoing cancer therapy varies, clarifying underlying causes in individual cases is critical for optimal cancer treatment. Although it is essential to individually analyze immune checkpoint inhibitor-treated patients for underlying pathologies for each AKI episode, these analyses have not been realized. Herein, we aimed to individually clarify the underlying causes of AKI in immune checkpoint inhibitor-treated patients using a new clustering approach with Shapley Additive exPlanations (SHAP).MethodsWe developed a gradient-boosting decision tree-based machine learning model continuously predicting AKI within 7 days, using the medical records of 616 immune checkpoint inhibitor-treated patients. The temporal changes in individual predictive reasoning in AKI prediction models represented the key features contributing to each AKI prediction and clustered AKI patients based on the features with high predictive contribution quantified in time series by SHAP. We searched for common clinical backgrounds of AKI patients in each cluster, compared with annotation by three nephrologists.ResultsOne hundred and twelve patients (18.2%) had at least one AKI episode. They were clustered per the key feature, and their SHAP value patterns, and the nephrologists assessed the clusters' clinical relevance. Receiver operating characteristic analysis revealed that the area under the curve was 0.880. Patients with AKI were categorized into four clusters with significant prognostic differences (p = 0.010). The leading causes of AKI for each cluster, such as hypovolemia, drug-related, and cancer cachexia, were all clinically interpretable, which conventional approaches cannot obtain.ConclusionOur results suggest that the clustering method of individual predictive reasoning in machine learning models can be applied to infer clinically critical factors for developing each episode of AKI among patients with multiple AKI risk factors, such as immune checkpoint inhibitor-treated patients.

BackgroundShareable e-scooters have become popular, but injuries to riders and bystanders have not been well characterized. The goal of this study was to describe e-scooter injuries and estimate the rate of injury per e-scooter trip.Methods and findingsRetrospective review of patients presenting to 180 clinics and 2 hospitals in greater Los Angeles between January 1, 2014 and May 14, 2020. Injuries were identified using a natural language processing (NLP) algorithm not previously used to identify injuries, tallied, and described along with required healthcare resources. We combine these tallies with municipal data on scooter use to report a monthly utilization-corrected rate of e-scooter injuries. We searched 36 million clinical notes. Our NLP algorithm correctly classified 92% of notes in the testing set compared with the gold standard of investigator review. In total, we identified 1,354 people injured by e-scooters; 30% were seen in more than one clinical setting (e.g., emergency department and a follow-up outpatient visit), 29% required advanced imaging, 6% required inpatient admission, and 2 died. We estimate 115 injuries per million e-scooter trips were treated in our health system.ConclusionsOur observed e-scooter injury rate is likely an underestimate, but is similar to that previously reported for motorcycles. However, the comparative severity of injuries is unknown. Our methodology may prove useful to study other clinical conditions not identifiable by existing diagnostic systems.

Plant root development involves multiple signal transduction pathways. Notably, phytohormones like auxin and cytokinin are well characterized for their molecular mechanisms of action. Reactive oxygen species (ROS) serve as crucial signaling molecules in controlling root development. The transcription factor, UPBEAT1 (UPB1) is responsible for maintaining ROS homeostasis at the root tip, influencing the transition from cell proliferation to differentiation. While UPB1 directly regulates peroxidase expression to control ROS homeostasis, it targets genes other than peroxidases, suggesting its involvement in root growth through non-ROS signals. Our investigation focused on the transcription factor MYB50, a direct target of UPB1, in Arabidopsis thaliana. By analyzing multiple fluorescent proteins and conducting RNA-seq and ChIP-seq, we unraveled a step in the MYB50 regulatory gene network. This analysis, in conjunction with the UPB1 regulatory network, demonstrated that MYB50 directly regulates the expression of PECTIN METHYLESTERASE INHIBITOR 8 (PMEI8). Overexpressing PMEI8, similar to the MYB50, resulted in reduced mature cell length. These findings establish MYB50 as a regulator of root growth within the UPB1 gene regulatory network. Our study presents a model involving transcriptional regulation by MYB50 in the UPB1 regulated root growth system and sheds light on cell elongation via pectin modification.

IntroductionRegulatory T cells (Tregs) have attracted attention as a novel therapeutic target to augment the clinical efficacy of immunotherapy. We conducted phase Ia and Ib trials to examine the safety and efficacy of the anti-CCR4 antibody, KW-0761 (mogamulizumab), which may eliminate effector Tregs (eTregs). We herein overviewed the results of these trials, presented cases with a durable clinical response, and investigated factors associated with the clinical effects of KW-0761.MethodsForty-nine patients with CCR4-negative solid cancers were enrolled in the phase Ia and Ib trials on KW-0761. An integral analysis of safety, clinical responses, prognosis, blood laboratory data, and cancer testis antigen-specific immune responses was performed.ResultsGrade 3-4 treatment-related adverse events were reported in 21 (42.9%) out of 49 patients, all of which were manageable. A partial response and stable disease were observed in 1 and 9 patients, respectively. A durable clinical response was noted in 2 esophageal and 2 lung cancer patients. eTreg depletion in peripheral blood was confirmed in most patients, and eTreg depletion was sustained during the KW-0761 treatment. High lymphocyte levels at baseline and 2 weeks after the initiation of KW-0761 were associated with a favorable clinical outcome.ConclusionsA durable clinical response was noted in some patients, and high lymphocyte levels before treatment initiation may be a biomarker for the efficacy of KW-0761. The synergistic effect of KW-0761 for depleting Tregs and other immunotherapies is expected in the future.

Aphasia nearly affects half of all poststroke patients. Furthermore, aphasia affects all language functions, well-being, and quality of life of patients. Therefore, rehabilitation of patients with aphasia requires an accurate assessment of language function and psychological aspects. However, assessment scales for language function and psychological aspects of patients with aphasia are said to be inaccurate. In Japan, this sign is more prominent than in English-speaking countries. Therefore, we are putting together a scoping review of research articles published in English and Japanese to date, with the aim of summarizing the accuracy of rating scales for language function and psychological aspects of people with aphasia. The scoping review was intended to be a comprehensive examination of the accuracy of rating scales for people with aphasia. We will search the article databases PubMed, MEDLINE, Embase, PsycINFO, Web of Science, and the Medical Journal Web (Japan). The observational studies that describe the reliability and validity of the rating scales in adult aphasic after stroke will be searched for. There will be no publication date for the articles that will be searched. We believe that this scoping review aims to assess the accuracy of rating scales used to measure different aspects of aphasia, with a focus on research conducted in English-speaking countries and Japan. By conducting this review, we believe to identify any problems with rating scales used in English and Japanese research and improve their accuracy.

Intestinal ischemia-reperfusion injury leads to proinflammatory responses via gut-derived mediators, and accumulating evidence suggests that exosomes secreted by intestinal epithelial cells are involved in the development of systemic inflammation. Studies have reported changes in protein, lipid, and microRNA (miRNA) expression; however, considering the different experimental conditions, information on the relationships among these biomolecules remains insufficient. The aim of this study was to elucidate the multiple changes that simultaneously occur in exosomes after ischemic stimulation. Here, differentiated human intestinal Caco-2 cells were exposed to 95% air (normoxia group) or 5% O2 (hypoxia group) for 6 h. Cells in each group were subsequently incubated for 24 h in an atmosphere of 5% CO2 plus 95% air. The conditioned medium of each group was collected for isolating intestinal epithelial cell-derived exosomes. Together with proteome analyses, lipid analyses, and miRNA quantification, biological functional assays were performed using monocytic NF-κB reporter cells. Lipid metabolism-related protein expression was upregulated, miRNA levels were slightly altered, and unsaturated fatty acid-containing lysophosphatidylcholine concentration increased after hypoxia and reoxygenation injury; this suggested that the changes in exosomal components associated with ischemia-reperfusion injury activates inflammation, including the NF-κB pathway. This study elucidated the multiple changes that co-occur in exosomes after ischemic stimulation and partially clarified the mechanism underlying exosome-mediated inflammation after intestinal ischemic recanalization.

PurposeTo compare the efficacy and invasiveness of manual gonioscopy and automated 360-degree gonioscopy.MethodManual and automated gonioscopy were performed on 70 patients with glaucoma. Manual gonioscopy was performed by a glaucoma specialist and an ophthalmology resident, and automated gonioscopy (GS-1) was performed by orthoptists. We compared the examination time for acquiring gonioscopic images (GS-1: 16 directions; manual gonioscopy: 8 directions). Furthermore, we compared the pain and discomfort scores during the examination using the Individualized Numeric Rating Scale. Among the images acquired by automated gonioscopy, we also evaluated the percentages of acquired images that could be used to determine the angle opening condition.ResultsThe examination time was not significantly different between manual (80.2±28.7) and automated gonioscopy (94.7±82.8) (p = 0.105). The pain score of automated gonioscopy (0.22±0.59) was significantly lower than that of manual gonioscopy (0.55±1.11) (p = 0.025). The discomfort score was not significantly different between manual (1.34±1.90) and automated gonioscopy (1.06±1.50) (p = 0.165). Automated gonioscopy successfully acquired clear gonioscopic images in 93.4% of the total images.ConclusionAutomated gonioscopy is comparable in examination time and invasiveness to manual gonioscopy and may be useful for 360-degree iridocorneal angle evaluation.

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.

Background Coronavirus disease 2019 (COVID-19) pneumonia can have prolonged sequelae and lead to respiratory dysfunction, mainly because of impaired diffusion capacity for carbon monoxide (DLCO). The clinical factors associated with DLCO impairment, including blood biochemistry test parameters, remain unclear. Methods Patients with COVID-19 pneumonia who underwent inpatient treatment between April 2020 and August 2021 were included in this study. A pulmonary function test was performed 3 months after onset, and the sequelae symptoms were investigated. Clinical factors, including blood test parameters and abnormal chest shadows on computed tomography, of COVID-19 pneumonia associated with DLCO impairment were investigated. Results In total, 54 recovered patients participated in this study. Twenty-six patients (48%) and 12 patients (22%) had sequelae symptoms 2 and 3 months after, respectively. The main sequelae symptoms at 3 months were dyspnea and general malaise. Pulmonary function tests showed that 13 patients (24%) had both DLCO 686.5 ng/mL (odds ratio: 11.08, 95% confidence interval [CI]: 1.84–66.59; p = 0.009) was most strongly associated with DLCO impairment. Conclusions Decreased DLCO was the most common respiratory function impairment, and ferritin level was a significantly associated clinical factor. Serum ferritin level could be used as a predictor of DLCO impairment in cases of COVID-19 pneumonia.

This study aims to compare the effectiveness of Hybrid and Pure problem-based learning (PBL) in teaching clinical reasoning skills to medical students. The study sample consisted of 99 medical students participating in a clerkship rotation at the Department of General Medicine, Chiba University Hospital. They were randomly assigned to Hybrid PBL (intervention group, n = 52) or Pure PBL group (control group, n = 47). The quantitative outcomes were measured with the students' perceived competence in PBL, satisfaction with sessions, and self-evaluation of competency in clinical reasoning. The qualitative component consisted of a content analysis on the benefits of learning clinical reasoning using Hybrid PBL. There was no significant difference between intervention and control groups in the five students' perceived competence and satisfaction with sessions. In two-way repeated measure analysis of variance, self-evaluation of competency in clinical reasoning was significantly improved in the intervention group in "recalling appropriate differential diagnosis from patient's chief complaint" (F(1,97) = 5.295, p = 0.024) and "practicing the appropriate clinical reasoning process" (F(1,97) = 4.016, p = 0.038). According to multiple comparisons, the scores of "recalling appropriate history, physical examination, and tests on clinical hypothesis generation" (F(1,97) = 6.796, p = 0.011), "verbalizing and reflecting appropriately on own mistakes," (F(1,97) = 4.352, p = 0.040) "selecting keywords from the whole aspect of the patient," (F(1,97) = 5.607, p = 0.020) and "examining the patient while visualizing his/her daily life" (F(1,97) = 7.120, p = 0.009) were significantly higher in the control group. In the content analysis, 13 advantage categories of Hybrid PBL were extracted. In the subcategories, "acquisition of knowledge" was the most frequent subcategory, followed by "leading the discussion," "smooth discussion," "getting feedback," "timely feedback," and "supporting the clinical reasoning process." Hybrid PBL can help acquire practical knowledge and deepen understanding of clinical reasoning, whereas Pure PBL can improve several important skills such as verbalizing and reflecting on one's own errors and selecting appropriate keywords from the whole aspect of the patient.

Dental caries and periodontal disease are typical oral diseases frequently observed in patients with renal diseases. Tooth loss is an outcome of dental caries and periodontal disease, and the number of existing teeth is an indicator of oral health status. However, the association between the number of existing teeth and end-stage kidney disease (ESKD) has not been investigated in detail. This study aimed to investigate the association between oral health status, expressed by the number of existing teeth, and ESKD. We analyzed data from the second survey of the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists, a cohort study conducted among members of the Japan Dental Association. From August 2016 to July 2017, self-administered questionnaires were mailed to 16,128 male dentists and 8,722 responded. Among them, 7,479 men with complete data on age, number of existing teeth, and ESKD were included in the analysis. Multivariate logistic regression analysis was conducted, with ESKD as the dependent variable and the number of existing teeth (≥23 teeth and <23 teeth) as the independent variable. Subgroup analysis by age (<65 years and ≥65 years) was also conducted. The <23 teeth group had a significantly higher rate of ESKD than did the ≥23 teeth group. After adjusting for age, body mass index, smoking habits, hypertension, and diabetes mellitus, there was no significant association between having <23 teeth and ESKD in all participants. However, the subgroup analysis revealed a significant association after adjustment for covariates in participants aged <65 years but not in those aged ≥65 years. In conclusion, having <23 teeth was associated with the risk of requiring maintenance dialysis therapy among Japanese men aged <65 years. Therefore, tooth loss may be associated with renal function decline. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to determine whether excessive maternal weight gain during pregnancy was associated with a higher risk of prolonged labor. Methods: We analyzed the data regarding maternal weight gain during pregnancy for the participants of Japan Environment and Children's Study (JECS), which is an ongoing nationwide prospective birth cohort study in Japan. After excluding participants with multiple pregnancies, with deliveries before 37 or beyond 42 weeks of gestation, or who had undergone cesarean section, 71,154 (nulliparous, n = 28,442) Japanese women were included. Prolonged labor was defined by a cutoff ranking at the 95th percentile and consequently defined as labor duration exceeding 12.7 h in multiparous women and exceeding 23.2 h in nulliparous women. These classifications were made according to labor curves established by the Japanese Society of Obstetrics and Gynecology Perinatal Committee developed in June 2021. Considering that no studies have conducted an investigation based on this new guideline, we analyzed the association between excessive maternal weight gain during pregnancy and prolonged labor by parity. Results: The overall incidence of prolonged labor was 10.2% (2,907/28,442) in nulliparous women and 6.1% (2,597/42,712) in multiparous women. Multivariable analysis indicated that excessive maternal weight gain was significantly associated with prolonged labor in nulliparous (adjusted odds ratio, 1.21; 95% confidence interval, 1.10–1.32) and multiparous women (adjusted odds ratio, 1.15; 95% confidence interval, 1.05–1.27). Kaplan–Meier survival analysis showed that as labor progressed, the percentage of women who had not yet delivered was higher among those with excessive maternal weight gain than among those with normal maternal weight gain in both the nulliparous (median labor duration 12.9 h vs 12.2 h, p<0.001) and multiparous (median labor duration 6.2 h vs 5.8 h, p<0.001) groups. Conclusion: Excessive maternal weight gain was significantly associated with prolonged labor in Japanese women. [ABSTRACT FROM AUTHOR]

BackgroundMen who have sex with men (MSM) and transgender women in Peru are at high risk for acquiring syphilis and HIV infection. The World Health Organization highly recommends screening for HIV and syphilis to reduce morbidity and mortality associated with untreated infections. We aimed to identify factors associated with dual testing preferences for HIV and syphilis infection among MSM and transgender women in Lima, Peru.MethodsWe used conjoint analysis, an innovative method for systematically estimating consumer preferences. We created eight hypothetical test profiles varying across six dichotomous attributes: cost (free vs. $4), potential for false positive syphilis result (no false positive vs. some risk of false positive), time-to-result (20 minutes vs. 1 week), blood draw method (finger prick vs. venipuncture), test type (rapid vs. laboratory), and number of draws (1 vs. 2). We fit a conjoint analysis model for each participant using a simple main effects ANOVA. Attribute importance values were calculated using percentages from relative ranges in the attribute's utility values. Results were summarized across participants and averages were reported.ResultsWe recruited 415 MSM/transgender women over 18 years of age from two STD clinics in Lima, Peru. No potential for syphilis false positive result (no false positive vs. some potential for false positive) had the largest average impact on willingness to use the test and on average accounted for 23.8% of test type preference, followed by cost (free vs. ~USD$4; 21.6%), time to results (20 minutes vs. 1 week; 17.4%), number of blood draws (1 draw vs. 2 draws; 13.8%), method of blood draw (fingerprick vs. venipuncture; 13.7%), and test type (rapid POC vs. laboratory; 9.7%).ConclusionMSM/transgender women in Peru prioritized accuracy, cost, timeliness and number of blood draws for HIV and syphilis testing. Implementing a low cost, accurate, rapid and dual testing strategy for HIV and syphilis could improve screening uptake and accessibility of testing to accelerate time to treatment.

Background: Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN. Methods: The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated. Results: In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis. Conclusions: The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression. [ABSTRACT FROM AUTHOR]

BackgroundOral health is a key factor of overall health and closely associated with well-being and quality of life. Mastication is one the most important oral functions and may deteriorate with aging. Evidence on association between masticatory dysfunction and frailty in the literature is scarce and not coherent.MethodsA search strategy was developed to conduct a systematic review of the literature in PubMed, CINAHL, and AMED in accordance with the PRISMA 2020 guidelines. We searched for studies published in 2000 or later that examined associations between self-reported masticatory dysfunction and frailty risk. The reference lists of the relevant articles were reviewed for additional studies. We calculated pooled odds ratios (OR) of association between self-reported masticatory dysfunction and the risk of frailty by fixed-effects meta-analysis. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess risk of bias. Publication bias was assessed by visually inspecting a funnel plot.ResultsA total of 285 studies were identified by the literature search. Among 5 studies selected for this review, 4 cross-sectional studies including a total of 7425 individuals were used for meta-analysis. The pooled results by a fixed-effects model showed that there was a significant association between self-reported masticatory dysfunction and frailty risk (pooled OR = 1.83, 95%CI = 1.55-2.18, pConclusionsThis systematic review and meta-analysis highlighted pooled cross-sectional evidence that community-dwelling older people who report masticatory dysfunction are significantly more likely to be frail than those who do not. The limitations of this study are: inclusion of only cross-sectional studies, no gold standard to measure masticatory functions, self-reported information on masticatory function, and the limited number of included studies. More longitudinal studies are warranted for further understanding of the causal pathways and elucidate underlying mechanisms. Registration: PROSPERO CRD42021277173.

BackgroundAutonomic dysfunction is a factor in irritable bowel syndrome (IBS). However, there are no reports of autonomic nervous system (ANS) activity during natural defecation in patients with IBS. We aimed to clarify the relationship between ANS activity and life events, such as defecation and abdominal symptoms, using real-time recording.MethodsSix patients with IBS and 14 healthy controls were enrolled in this prospective multicenter study. ANS activity was recorded for 24 h using a T-shirt wearable device, and life events were recorded simultaneously in real time using a smartphone application software. Low frequency/high frequency (LF/HF) and HF calculated by power spectrum analysis were defined as activity indicators of the sympathetic and parasympathetic nerves, respectively.ResultsThe means of LF/HF and HF in the period with positive symptoms were comparable between the groups; however, the sum of LF/HF, sum of ΔLF/HF, and the maximum variation in ΔLF/HF were significantly higher in the IBS group. In the IBS group, the sum of ΔLF/HF and LF/HF increased significantly from 2 min before defecation, and the sum of LF/HF remained significantly higher until 9 min after defecation. The sum of ΔLF/HF at 2 min before defecation was significantly positively correlated with the intensity of abdominal pain and diarrhea and constipation scores. In contrast, it was significantly negatively correlated with defecation satisfaction and health-related quality of life.ConclusionsIn patients with IBS, sympathetic nerve activity was activated 2 min before defecation, which was correlated with abdominal symptoms and lower QOL.

Cardiac implantable electrical devices (CIED) such as pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapies are generally recommended for older patients and those with severe heart failure (HF). However, there is currently a lack of evidence on the relationship between frailty and readmission rates among patients with CIED. This study investigated whether preoperative frailty influenced readmission rates among patients with CIED over a one-year period following implantation. The study retrospectively analyzed 101 patients who underwent CIED implantations. To compare frailty-based differences in their characteristics and readmission rates, these participants were categorized into frailty and non-frailty groups via the modified frailty index (mFI). The frailty group had a significantly higher readmission rate than the non-frailty group (non-frailty group vs. frailty group = 1 vs. 8 patients: P < 0.05). Further, a multivariate analysis showed that frailty was a significant readmission factor. Based on individual analyses with/without histories of HF, the readmission rate also tended to be higher among individuals considered frail via the mFI (readmission rate in HF patients: non-frailty group vs. frailty group = 1 vs. 5 patients: P = 0.65; non-HF patients: non-frailty group vs. frailty group = 0 vs. 3 patients: P = 0.01). Participants with preoperative frailty showed higher readmission rates within a one-year period following implantation compared to those without preoperative frailty. This tendency was consistent regardless of HF history. The mFI may thus help predict readmission among patients with CIED.

We aimed to determine the risk of perinatal complications during delivery in mothers with non-normal glucose tolerance in a large Japanese birth cohort. We analysed data of 24,295 neonate–mother pairs in the Japan Environment and Children’s Study cohort between 2011 and 2014. We included 67 mothers with type 1 diabetes, 102 with type 2 diabetes (determined by questionnaire), 2,045 with gestational diabetes (determined by diagnosis), and 2,949 with plasma glucose levels ≥140 mg/dL (shown by a screening test for gestational diabetes). Gestational age, birth weight, placental weight, and proportions of preterm birth, and labour and neonatal complications at delivery in mothers with diabetes were compared with those in mothers with normal glucose tolerance. Mean gestational age was shorter in mothers with any type of diabetes than in mothers without diabetes. Birth weight tended to be heavier in mothers with type 1 diabetes, and placental weight was significantly heavier in mothers with type 1 and gestational diabetes and elevated plasma glucose levels (all p

Helicobacter pylori (H. pylori) is widely known as a cause of gastric disorders. Presence of H. pylori in dental pulp has been reported. Dental caries may influence the presence or absence of systemic H. pylori infection by serving as a source of H. pylori. In this cross-sectional study, we examined whether H. pylori infection in blood were associated with dental caries in Japanese adults. The participants were 752 individuals (513 males and 239 females, mean age 53.8 years) who underwent both H. pylori testing (H. pylori antibody test and pepsinogen test) and dental checkups at the Asahi University Hospital Human Health Center between April 2018 and March 2019. Those diagnosed as positive for H. pylori antibody test or positive for serum pepsinogen test as H. pylori test in the human health checkup were judged as those with H. pylori infection in the blood. In our study, 83 participants (11%) were determined to be infected with H. pylori in the blood. The proportion of those with decayed teeth was higher in participants with H. pylori infection in blood than in those without H. pylori infection in blood (p< 0.001). The logistic analysis showed that presence of H. pylori infection in blood was positively associated with those with decayed teeth (OR, 5.656; 95% CI, 3.374 to 9.479) after adjusting for age, gender, gastric disease, regular dental checkups, antibiotic medication history, and decayed teeth. Furthermore, the proportion of H. pylori infection in blood increased according to number of decayed teeth (p< 0.001). The results indicate that H. pylori infection in blood were associated with decayed teeth. Untreated dental caries may have an impact on systemic H. pylori infection.

The present study was conducted to determine the effect of endurance exercise under low energy availability (EA) on exogenous glucose oxidation during endurance exercise. Ten active males (21.4 ± 0.6 years, 170.4 ± 1.4 cm, 62.4 ± 1.5 kg, 21.5 ± 0.4 kg/m2) completed two trials, consisting of two consecutive days (days 1 and 2) of endurance training under low EA (19.9 ± 0.2 kcal/kg fat free mass [FFM]/day, LEA trial) or normal EA (46.4 ± 0.1 kcal/kg FFM/day, NEA trial). The order of these two trials was randomized with at least a 1-week interval between trials. As an endurance training, participants performed 60 min of treadmill running at 70% of maximal oxygen uptake (

Cholesteatoma is a progressive middle ear disease that can only be treated surgically but with a high recurrence rate. Depending on the extent of the disease, a surgical approach, such as microsurgery with a retroarticular incision or transcanal endoscopic surgery, is performed. However, the current examination cannot sufficiently predict the progression before surgery, and changes in approach may be made during the surgery. Large amounts of data are typically required to train deep neural network models; however, the prevalence of cholesteatomas is low (1-in-25, 000). Developing analysis methods that improve the accuracy with such a small number of samples is an important issue for medical artificial intelligence (AI) research. This paper presents an AI-based system to automatically detect mastoid extensions using CT. This retrospective study included 164 patients (80 with mastoid extension and 84 without mastoid extension) who underwent surgery. This study adopted a relatively lightweight neural network model called MobileNetV2 to learn and predict the CT images of 164 patients. The training was performed with eight divided groups for cross-validation and was performed 24 times with each of the eight groups to verify accuracy fluctuations caused by randomly augmented learning. An evaluation was performed by each of the 24 single-trained models, and 24 sets of ensemble predictions with 23 models for 100% original size images and 400% zoomed images. Fifteen otolaryngologists diagnosed the images and compared the results. The average accuracy of predicting 400% zoomed images using ensemble prediction model was 81.14% (sensitivity = 84.95%, specificity = 77.33%). The average accuracy of the otolaryngologists was 73.41% (sensitivity, 83.17%; specificity, 64.13%), which was not affected by their clinical experiences. Noteworthily, despite the small number of cases, we were able to create a highly accurate AI. These findings represent an important first step in the automatic diagnosis of the cholesteatoma extension.

This study aimed to investigate the incidence, patient background, and postoperative prognosis of implantable collamer lens (ICL) dislocation. We retrospectively reviewed all cases of ICL dislocation at four major refractive surgery centers in Japan until December 2019. The incidence, patient background, cause of dislocation, complications of repositioning surgery, and postoperative visual function were investigated. Seven ICL dislocations [0.072% of total ICL-implanted eyes (9775 eyes)] occurred at an average of 28.6 months (11–82 months) postoperatively. All patients were male. Five eyes were injured during sports activities, one due to a fall from a bicycle, and another due to ocular blunt trauma caused by a mortuary tablet. Two patients had re-dislocation in the same eye. Retinal detachment occurred after repositioning surgery in one patient, and scleral buckling surgery was performed without ICL removal. ICL dislocation is a rare complication of ICL surgery; repositioning surgery is effective, but retinal complications may occur.

ObjectiveTo determine the climate conditions that affect the incidence of atopic dermatitis from infancy to 3 years old.Study designWe analyzed 100,303 children born from 2011 to 2014 for follow-up until 3 years old using cohort data from the Japan Environment and Children's Study. The study included 15 Regional Centers, including 19 prefectures across Japan. We used meteorological data of the Japan Meteorological Agency. We calculated the hazard ratio (HR) of the standard deviation and low vs. high mean values of several climate conditions in children in their first 6 months of life to determine the incidence of atopic dermatitis.ResultsThe Kaplan-Meier curve showed that children born in the months of October to December had the highest incidence of atopic dermatitis. Among climate conditions, a one standard deviation increase in the temperature (HR = 0.87), minimum temperature (HR = 0.87), and vapor pressure (HR = 0.87) showed the lowest HRs for the incidence of atopic dermatitis. These results were confirmed by an analysis by strata of the birth season. A low vapor pressure (HR = 1.26, pConclusionAmong climate conditions, a low vapor pressure is the most strongly associated with a high incidence of atopic dermatitis. Measuring vapor pressure may be useful for preventing atopic dermatitis.

Purpose Diabetic patients often have systemic circulation diseases which may cause serious systemic complications during ophthalmic surgeries with local anesthesia. The purpose of this study is to evaluate the intraoperative alteration of the vital signs in diabetic patients during cataract surgery with local anesthesia. Methods Clinical records of 428 patients who underwent cataract surgeries with local anesthesia were reviewed. The parameters measured were systolic/diastolic blood pressures and pulse rates at pre-operation, 5, 10 and 15 minutes during the surgeries. The factors were compared between non-diabetic patients (n = 325) and diabetic patients (n = 103). Results Diabetic patients had significantly higher fasting blood sugar and preoperative pulse rate. Diabetic patients showed significantly higher systolic blood pressure compared to non-diabetic patients at 5 and 10 minutes from the beginning of surgery (p = 0.0093 and 0.0075, respectively). In the non-diabetic patients, the pulse rate was significantly decreased at 5 minutes from the beginning of surgery (p = 4.74 x 10−8) which was maintained during the surgery, but no change was observed in the pulse rate of the diabetic patients. Conclusions Diabetic patients showed higher systolic blood pressure and pulse rate during cataract surgeries with local anesthesia, which should be monitored carefully by the physicians to avoid possible systemic complications.

BackgroundShareable e-scooters have become popular, but injuries to riders and bystanders have not been well characterized. The goal of this study was to describe e-scooter injuries and estimate the rate of injury per e-scooter trip.Methods and findingsRetrospective review of patients presenting to 180 clinics and 2 hospitals in greater Los Angeles between January 1, 2014 and May 14, 2020. Injuries were identified using a natural language processing (NLP) algorithm not previously used to identify injuries, tallied, and described along with required healthcare resources. We combine these tallies with municipal data on scooter use to report a monthly utilization-corrected rate of e-scooter injuries. We searched 36 million clinical notes. Our NLP algorithm correctly classified 92% of notes in the testing set compared with the gold standard of investigator review. In total, we identified 1,354 people injured by e-scooters; 30% were seen in more than one clinical setting (e.g., emergency department and a follow-up outpatient visit), 29% required advanced imaging, 6% required inpatient admission, and 2 died. We estimate 115 injuries per million e-scooter trips were treated in our health system.ConclusionsOur observed e-scooter injury rate is likely an underestimate, but is similar to that previously reported for motorcycles. However, the comparative severity of injuries is unknown. Our methodology may prove useful to study other clinical conditions not identifiable by existing diagnostic systems.

Nonverbal communication with people who have physical disabilities is difficult. Eye-tracking technologies have recently been developed and applied to help people with physical disabilities in their communication. However, the eye-gaze patterns of people with severe motor dysfunction (SMD) have not been analyzed in detail. To clarify characterization of people with SMD, we aimed to develop gaze position-based evaluation metrics and analyze detailed eye-gaze patterns of people with SMD. We developed two new scoring metrics: (1) saliency score based on three saliency maps-spectral residual (SR), fine grained (FG), and motion (Mo); and (2) the distance score, which represents to what extent people can chase an object in a video. The evaluation was performed on 102 participants, consisting of 35 subjects with profound intellectual and multiple disabilities (PIMD; SMD with IQ < 20), 19 with severe physical disabilities (SPD; SMD with IQ ≥ 20), and 48 healthy individuals. We observed that two saliency scores (SR and FG) and the distance score showed significant differences between the PIMD/SPD and healthy groups for the entire video, whereas Mo scores did not. Moreover, the distance score was analyzed separately for each scene, where scenes were categorized into three patterns-running, explanation, and hiding-according to the behavior of the moving objects. In the SPD and healthy groups, the explanation scenes accounted for the highest percentage of all scenes with the best distance score (63.6% and 61.9%, respectively), whereas in the PIMD group, the running scenes accounted for the highest percentage (54.5%). In conclusion, the new metrics were successful in quantitatively assessing the gaze responsiveness of people with SMD, which could not be assessed using a conventional metric, gaze-acquisition time. This study is expected to expand the possibilities of nonverbal communication using eye-tracking devices for people with SMD.

IntroductionThe interaction of CD155 with its ligand, the T cell immunoreceptor with Ig and ITIM domains (TIGIT), is being studied owing to its potential to act as a target in the treatment of various solid tumors. However, the relationship between CD155 and TIGIT in colorectal cancer (CRC) prognosis is not known. We hypothesized that the TIGIT-CD155 pathway suppresses the attack of T cells on tumors, thereby affecting CRC prognosis.MethodsWe examined the expression of CD155 and TIGIT using immunohistochemical staining in 100 consecutive patients with CRC who underwent complete resection of ≤Stage III tumors at Wakayama Medical University Hospital between January and December 2013. We assessed the correlation between CD155 and TIGIT expressions and prognosis as well as the clinicopathological background of CD155 and TIGIT.ResultsPatients with high CD155 and TIGIT expressions showed worse prognosis than those with other levels of expression (p = 0.026). In multivariate analysis that also included the existing prognostic markers, high CD155 and TIGIT expressions were identified as independent poor prognostic factors.ConclusionsThe interaction between CD155 and TIGIT possibly plays an important role in the immunological mechanism of CRC. Therefore, it may be possible to effectively predict the postoperative prognosis of CRC by evaluating the combined expression of CD155 and TIGIT. The study findings suggest that CD155 and TIGIT can predict clinical outcomes, thereby contributing to the personalized care of CRC.

[This corrects the article DOI: 10.1371/journal.pone.0243702.].

BackgroundThe aim of our study was to evaluate the influence of changes of nutritional status and body composition on the results of comprehensive geriatric assessment (CGA) in inpatients of a geriatric ward. Sex differences in these relationships were also investigated.MethodsA total of 212 elderly patients (>65 years old) admitted to the geriatric ward at the University of Tokyo hospital between 2012 and 2019 were enrolled in this study. CGA (ADL, IADL, MMSE, GDS, Vitality Index) was performed, along with assessment of body compositions (appendicular muscle mass, abdominal muscle mass, body fat mass) and blood malnutrition biomarkers (serum albumin, pre-albumin, 25-hydroxy vitamin D, zinc, hemoglobin concentrations).ResultsMultiple linear regression analysis showed that upper, lower limbs and abdominal muscle masses were significantly associated with the score on ADL in men. On the other hand, abdominal muscle mass was negatively associated with the scores on GDS. Body fat mass was also negatively associated with the score on IADL. In contrast, in women, multiple linear regression analysis failed to show any significant associations between body composition parameters and scores on any domains of CGA. Unlike in men, however, blood malnutrition biomarkers were significantly associated with ADL, IADL, MMSE, and Vitality Index in women.ConclusionsOur study findings revealed that the association of the nutritional status and body composition with the functional status in the elderly differs by sex. These results suggest that intensification of exercise in men and improvement of the nutritional status in women are particularly useful to maintain the functional status.

Obesity is a major risk factor for various chronic diseases such as diabetes, cardiovascular disease, and cancer; hence, there is an urgent need for an effective strategy to prevent this disorder. Currently, the anti-obesity effects of food ingredients are drawing attention. Therefore, we focused on carob, which has high antioxidant capacity and various physiological effects, and examined its anti-obesity effect. Carob is cultivated in the Mediterranean region, and its roasted powder is used as a substitute for cocoa powder. We investigated the effect of carob pod polyphenols (CPPs) on suppressing increases in adipose tissue weight and adipocyte hypertrophy in high fat diet-induced obesity model mice, and the mechanism by which CPPs inhibit the differentiation of 3T3-L1 preadipocytes into adipocytes in vitro. In an in vivo experimental system, we revealed that CPPs significantly suppressed the increase in adipose tissue weight and adipocyte hypertrophy. Moreover, in an in vitro experimental system, CPPs acted at the early stage of differentiation of 3T3-L1 preadipocytes and suppressed cell proliferation because of differentiation induction. They also suppressed the expression of transcription factors involved in adipocyte differentiation, thereby reducing triacylglycerol synthesis ability and triglycerol (TG) accumulation. Notably, CPPs regulated CCAAT/enhancer binding protein (C/EBP)β, which is expressed at the early stage of differentiation, at the posttranscriptional level. These results demonstrate that CPPs suppress the differentiation of adipocytes through the posttranscriptional regulation of C/EBPβ and may serve as an effective anti-obesity compound.

BackgroundDelayed identification of infiltration and dysfunction of peripheral intravenous (PIV) access can lead to serious consequences during general anesthesia in children. This preliminary study aimed to describe the application of precordial Doppler ultrasound during general anesthesia in children to detect and confirm the correct PIV access and to evaluate the accuracy of this method.MethodsThis was a single-center, preliminary study that was conducted in children (ResultsThe total incidence of peripheral infiltration and dysfunction of PIV catheter was 7/512 (1.4%). In the S test, the sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver-operating characteristic curves (AUCs) were 5/7 (71.4%; 95% confidence interval [CI], 29.0%-96.3%), 490/505 (97.0%; 95% CI, 95.1%-98.3%), 24.0, 0.29, and 0.84, respectively. The V test showed that the reasonable threshold of blood flow velocity change was 1.0 m/s, with sensitivity, specificity, positive and negative likelihood ratios, and AUC of 4/7 (57.1%; 95% CI, 18.4%-90.1%), 489/505 (96.8%; 95% CI, 94.9%-98.2%), 18.0 and 0.44, and 0.84, respectively.ConclusionsThis preliminary study demonstrated that precordial Doppler ultrasound is a feasible, easy-to-use, and noninvasive technique with good accuracy to confirm the correct PIV access during general anesthesia in children. However, its accuracy requires further evaluation.

PurposeTo evaluate the age-related change in color visual acuity (CVA) in normal eyes.MethodsIn total, 162 normal eyes (162 subjects, women: 52, men: 110, age range: 15-68 years) with best-corrected visual acuity (BCVA) ≥20/13 were enrolled. Fifteen colors from the New Color Test (chroma 6) were applied to Landolt "C" rings, white point D65 was applied as background, and a luminance of 30 cd/m2 was set for both the rings and the background. These rings were used to measure the chromatic spatial discrimination acuity as the CVA value, while changing the stimulus size. Correlations of the CVA value of each color and age were evaluated. Mean CVA values of all 15 colors (logarithm of the minimum angle of resolution) were compared between age groups in 10-year increments.ResultsNine CVA values (red, yellow-red, red-yellow, green, blue-green, green-blue, purple, red-purple, and purple-red) were negatively correlated with age (all pConclusionsThe CVA values related to the medium/long-wavelength-sensitive cones were more susceptible to aging than those related to the short-wavelength-sensitive cones. This differed from previous reports, and may be related to the difference in the range of foveal cone function evaluated with each examination.

ObjectivesWe previously reported the diagnostic and prognostic performance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma as amyotrophic lateral sclerosis (ALS) biomarkers. The present study aimed to elucidate associations between clinical characteristics and the markers as well as mutual associations of the markers in ALS patients using the same dataset.MethodsNfL, TDP-43, and t-tau levels in CSF and plasma in 75 ALS patients were analyzed. The associations between those markers and clinical details were investigated by uni- and multivariate analyses. Correlations between the markers were analyzed univariately.ResultsIn multivariate analysis of CSF proteins, the disease progression rate (DPR) was positively correlated with NfL (β: 0.51, p = 0.007) and t-tau (β: 0.37, p = 0.03). Plasma NfL was correlated with age (β: 0.53, p = 0.005) and diagnostic grade (β: -0.42, p = 0.02) in multivariate analysis. Plasma TDP-43 was correlated negatively with split hand index (β: -0.48, p = 0.04) and positively with % vital capacity (β: 0.64, p = 0.03) in multivariate analysis. Regarding mutual biomarker analysis, a negative correlation between CSF-NfL and TDP-43 was identified (r: -0.36, p = 0.002).ConclusionsElevated NfL and t-tau levels in CSF may be biomarkers to predict rapid DPR from onset to sample collection. The negative relationship between CSF NfL and TDP-43 suggests that elevation of CSF TDP-43 in ALS is not a simple consequence of its release into CSF during neurodegeneration. The negative correlation between plasma TDP-43 and split hand index may support the pathophysiological association between plasma TDP-43 and ALS.

The eligibility of COVID-19 vaccines has been expanded to children aged 12 and above in several countries including Japan, and there is a plan to further lower the age. This study aimed to assess factors related to parental COVID-19 vaccine hesitancy. A nationwide internet-based cross-sectional study was conducted between May 25 and June 3, 2021 in Japan. The target population was parents of children aged 3-14 years who resided in Japan, and agreed to answer the online questionnaire. Parental COVID-19 vaccine hesitancy (their intention to vaccinate their child) and related factors were analyzed using logistic regression models. Interaction effects of gender of parents and their level of social relationship satisfaction related to parental vaccine hesitancy was tested using log likelihood ratio test (LRT). Social media as the most trusted information source increased parental vaccine hesitancy compared to those who trusted official information (Adjusted Odds Ratio: aOR 2.80, 95% CI 1.53-5.12). Being a mother and low perceived risk of infection also increased parental vaccine hesitancy compared to father (aOR 2.43, 95% CI 1.57-3.74) and those with higher perceived risk of infection (aOR 1.55, 95% CI 1.04-2.32) respectively. People with lower satisfaction to social relationships tended to be more hesitant to vaccinate their child among mothers in contrast to fathers who showed constant intention to vaccinate their child regardless of the level of satisfaction to social relationship (LRT p = 0.021). Our findings suggest that dissemination of targeted information about COVID-19 vaccine by considering means of communication, gender and people who are isolated during measures of social distancing may help to increase parental vaccine acceptance.

BackgroundThe wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, PST) is responsible for significant yield losses in wheat production worldwide. In spite of its economic importance, the PST genomic sequence is not currently available. Fortunately Next Generation Sequencing (NGS) has radically improved sequencing speed and efficiency with a great reduction in costs compared to traditional sequencing technologies. We used Illumina sequencing to rapidly access the genomic sequence of the highly virulent PST race 130 (PST-130).Methodology/principal findingsWe obtained nearly 80 million high quality paired-end reads (>50x coverage) that were assembled into 29,178 contigs (64.8 Mb), which provide an estimated coverage of at least 88% of the PST genes and are available through GenBank. Extensive micro-synteny with the Puccinia graminis f. sp. tritici (PGTG) genome and high sequence similarity with annotated PGTG genes support the quality of the PST-130 contigs. We characterized the transposable elements present in the PST-130 contigs and using an ab initio gene prediction program we identified and tentatively annotated 22,815 putative coding sequences. We provide examples on the use of comparative approaches to improve gene annotation for both PST and PGTG and to identify candidate effectors. Finally, the assembled contigs provided an inventory of PST repetitive elements, which were annotated and deposited in Repbase.Conclusions/significanceThe assembly of the PST-130 genome and the predicted proteins provide useful resources to rapidly identify and clone PST genes and their regulatory regions. Although the automatic gene prediction has limitations, we show that a comparative genomics approach using multiple rust species can greatly improve the quality of gene annotation in these species. The PST-130 sequence will also be useful for comparative studies within PST as more races are sequenced. This study illustrates the power of NGS for rapid and efficient access to genomic sequence in non-model organisms.

[This corrects the article DOI: 10.1371/journal.pone.0223447.].

BACKGROUND:Hepcidin is an iron regulating hormone, and exercise-induced hepcidin elevation is suggested to increase the risk of iron deficiency among athletes. OBJECTIVE:We compared serum hepcidin responses to resistance exercise and endurance (cycling) exercise. METHODS:Ten males [mean ± standard error: 172 ± 2 cm, body weight: 70 ± 2 kg] performed three trials: a resistance exercise trial (RE), an endurance exercise trial (END), and a rest trial (REST). The RE consisted of 60 min of resistance exercise (3-5 sets × 12 repetitions, 8 exercises) at 65% of one repetition maximum, while 60 min of cycling exercise at 65% of [Formula: see text] was performed in the END. Blood samples were collected before exercise and during a 6-h post-exercise (0h, 1h, 2h, 3h, 6h after exercise). RESULTS:Both RE and END significantly increased blood lactate levels, with significantly higher in the RE (P < 0.001). Serum iron levels were significantly elevated immediately after exercise (P < 0.001), with no significant difference between RE and END. Both the RE and END significantly increased serum growth hormone (GH), cortisol, and myoglobin levels (P < 0.01). However, exercise-induced elevations of GH and cortisol were significantly greater in the RE (trial × time: P < 0.001). Plasma interleukin-6 (IL-6) levels were significantly elevated after exercise (P = 0.003), with no significant difference between the trials. Plasma hepcidin levels were elevated after exercise (P < 0.001), with significantly greater in the RE (463 ± 125%) than in the END (137 ± 27%, P = 0.03). During the REST, serum hepcidin and plasma IL-6 levels did not change significantly. CONCLUSION:Resistance exercise caused a greater exercise-induced elevation in hepcidin than did endurance (cycling) exercise. The present findings indicate that caution will be required to avoid iron deficiency even among athletes in strength (power) types of events who are regularly involved in resistance exercise.

Ribonuclease H2 (RNase H2) exhibits both single ribonucleotide excision activity (activity A) and RNA strand degrading activity (activity B). Val143 of human RNase H2 is located at the active site and is conserved in eukaryotic RNase H2. In this study, we explored the role of Val143 in catalytic activity and substrate specificity. Nineteen single variants at amino acid position 143 were expressed in E. coli, and all variants except for V143C and V143M were purified from the cells. When the activity of the wild-type human RNase H2 (WT) was set as 100%, the relative activities A and B of the 17 variants were in the range of 0.05-130 and 0.02-42%, respectively. When the ratio of the relative activity A to the relative activity B of WT was set as 1, the ratios of the 17 variants were in the range of 0.2-5.7. This indicates that valine is optimal for balancing the two activities. The ratios for V143Y and V143W were relatively high (5.6 and 5.5, respectively), suggesting that the bulky residues like tyrosine and tryptophan at position 143 caused steric hindrance with the 2'-OH of the sugar moiety of the ribonucleotide at the 5' side of the scissile phosphodiester bond. The ratio for V143Q was relatively low (0.2). These results suggested that Val143 is not critical for, but plays a role in determining catalytic activity and substrate specificity.

PURPOSE:The current study investigated differences in the peripapillary and macular choroidal areas between patients with primary open-angle glaucoma (POAG) and healthy controls because the choroid may potentially play a role in glaucoma pathophysiology. METHODS:We assessed 57 healthy controls and 42 POAG patients in a cross-sectional comparative study. We used enhanced depth imaging optical coherence tomography (EDI-OCT) and then converted the luminal and interstitial areas to binary images using the Niblack method to obtain peripapillary and macular choroidal images. The relationship between the choroidal area and demographic and ocular characteristics were determined with univariate and multivariate linear regression analysis. RESULTS:Regarding the peripapillary choroidal area, no significant differences were noted between healthy controls and POAG patients (1,836,336 ± 605,617 μm2 vs. 1,775,566 ± 477,317 μm2, respectively, P = 0.60). There were also no differences found for the macular choroidal area (controls: 347,220 ± 115,409 μm2, patients: 342,193 ± 104,356 μm2, P = 0.83). Multivariate regression analysis in the POAG patients revealed there was a significant relationship between the macular choroidal area and age (β = -0.525, P = 0.002) and axial length (β = -0.458, P = 0.005). In contrast, no correlation was found between peripapillary choroidal areas and various attributes in the POAG patients. CONCLUSIONS:EDI-OCT showed no differences in the peripapillary or macular choroidal area in healthy individuals compared to POAG patients.