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For older patients with displaced femoral neck fractures, in which primary osteosynthesis is usually not indicated, there are three primary prosthetic options-bipolar hemiarthroplasty (BHA), single-bearing total hip arthroplasty (SB-THA), and dual-mobility THA (DM-THA). However, the optimal choice for managing displaced femoral neck fractures remains controversial. Accordingly, this study aimed to evaluate the cost-effectiveness of BHA, SB-THA, and DM-THA in active older patients with displaced femoral neck fractures. A decision tree combined with a Markov model was employed to analyze the cost and quality-adjusted life years (QALYs) of BHA, SB-THA, and DM-THA for the management in the Japanese healthcare system. By simulating the five-year trajectory of a 75-year-old woman treated for a displaced femoral neck fracture, the cost-effectiveness of the three surgical options was evaluated. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were used to assess parameter uncertainty. Additionally, two scenario analyses were conducted for other settings. The treatment was considered to be cost-effective when the incremental cost-effectiveness ratio (ICER) was below the 5,000,000 yen/QALY threshold. Compared with BHA, SB-THA exhibited higher costs but greater health benefits, resulting in an ICER of 1,499,440 yen/QALY. DM-THA offered additional health benefits compared with SB-THA, with an ICER of 4,145,777 yen/QALY. One-way sensitivity analysis revealed some influential parameters. PSA indicated that the probability of DM-THA, SB-THA, and BHA being cost-effective was 40.1%, 38.5%, and 21.4%, respectively. SB-THA was more cost-effective than BHA in patients aged 65-85 years, while DM-THA was more cost-effective than SB-THA in patients aged 65-75 years. The results suggest that SB-THA is a cost-effective alternative to BHA for displaced femoral neck fractures in active older patients, whereas DM-THA is more cost-effective than SB-THA in relatively younger patients. It is, therefore, recommended that orthopedic surgeons select the most appropriate surgical option based on the individual patient's physiological age., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yokoyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An orthosis is often used in rehabilitation to improve kinetic and kinematic parameters during gait. However, whether changes in neural control depend on wearing an orthosis during gait is unclear. We measured the muscle activity and synergy of the lower limb muscles without orthosis and with two types of orthoses: ankle-foot orthosis (AFO) and knee-ankle-foot orthosis (KAFO). Muscle activity during gait was measured in 15 healthy adults, and muscle synergies were extracted using non-negative matrix factorization. The results revealed that some muscle activities were significantly different among the three conditions. Post-hoc analysis indicated differences between each condition. Knee extensor muscle activity related to the loading response was significantly increased by wearing the AFO. In the KAFO condition, hip abductor muscle activity related to weight bearing was significantly decreased, and ankle dorsiflexor muscle activity was increased to secure clearance during the swing phase. However, the number of muscle synergies and complexity of muscle synergy did not significantly change among these conditions. However, along with changes in muscle activity, the activation pattern and weightings of muscle synergies tended to change with the use of orthoses. Each muscle activity was changed by wearing the orthosis; however, the immediate mechanical constraint did not change the framework of muscle synergy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hashiguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) has a high mortality and requires effective treatment with anti-MRSA agents such as vancomycin (VCM). Management of the efficacy and safety of VCM has been implemented with the assignment of pharmacists in hospital wards and the establishment of teams related to infectious diseases. However, there are no reports evaluating the association between these factors and the efficacy and safety of VCM in large populations., Methods: This study used the Japanese administrative claims database accumulated from 2010 to 2019. The population was divided into two groups, therapeutic drug monitoring (TDM) group and non-TDM group, and adjusted by propensity score matching. We performed multivariate logistic regression analysis to determine the influence of pharmacists and infection control teams or antimicrobial stewardship teams on acute kidney injury (AKI) and 30-day mortality., Results: The total number of patients was 73 478 (TDM group, n = 55 269; non-TDM group, n = 18 209). After propensity score matching, 18 196 patients were matched in each group. Multivariate logistic regression analysis showed that pharmacological management for each patient contributed to the reduction of AKI (odds ratio [OR]: 0.812, 95% confidence interval [CI]: 0.723‒0.912) and 30-day mortality (OR: 0.538, 95% CI: 0.503‒0.575). However, the establishment of infectious disease associated team in facilities and the assignment of pharmacists in the hospital wards had no effect on AKI and 30-day mortality. In addition, TDM did not affect the reduction in AKI (OR: 1.061, 95% CI: 0.948‒1.187), but reduced 30-day mortality (OR: 0.873, 95% CI: 0.821‒0.929)., Conclusion: Pharmacologic management for individual patients, rather than assignment systems at facilities, is effective to reduce AKI and 30-day mortality with VCM administration., Competing Interests: Yuichi Muraki received an honorarium for lecturing from Pfizer Japan Inc. The other authors have no conflicts of interest to declare.

Background: Neck motor tics in Tourette's syndrome can cause severe neck complications. Although addressed in a few longitudinal studies, the clinical course of Tourette's syndrome has not been quantitatively assessed. We had previously developed a method for quantifying the angular movements of neck tics using a compact gyroscope. Here, we present a follow-up study aimed at elucidating the clinical course of neck tics at both the group and individual levels., Methods: Eleven patients with Tourette's syndrome from our previous study participated in the present study, and their neck tics were recorded during a 5-min observation period. The severity of neck symptoms was assessed using the Yale Global Tic Severity Scale. The peak angular velocities and accelerations, tic counts, and severity scores in our previous study (baseline) and the present study (2-year follow-up) were compared at the group and individual levels. The individual level consistency between baseline and follow-up were calculated using intra-class correlation coefficients (ICCs, one-way random, single measure)., Results: At the group level, no significant change was observed between baseline and follow-up. At the individual level, angular velocity (ICC 0.73) and YGTSS scores (ICC 0.75) had substantial consistency over the two time points, and angular acceleration (ICC 0.59) and tic counts (ICC 0.69) had moderate consistency., Conclusions: The intensity and frequency of neck tics did not change over time. Therefore, quantification of angular neck motor tics will aid in identifying patients with neck tics at high risk for severe neck complications., Competing Interests: The authors have declared that no competing interests exist.

Thailand has the highest road traffic fatality rate in Southeast Asia, making road safety a critical public health concern. A 2015 World Health Organization (WHO) Report showed that speeding behavior was the most important determinant for road traffic crashes in Thailand. Here, we aimed to examine associations of socio-demographic factors (gender, age, socioeconomic status) with self-reported motorcycle speeding behavior. Additionally, we examined a potential role of time discounting and risk preference as mediators in the association of socio-demographic factors with speeding. We used data obtained from the Mahasarakham University Social Network Survey 2018 (MSUSSS) (N = 150). We ran linear network autocorrelation models (lnam) to account for the data's social network structure. We found that males are more likely than females to engage in speeding behavior (β = 0.140, p = 0.001) and to discount the future (β = 5.175, p = 0.017). However, further causal mediation analysis showed that time discounting does not mediate the gender-speeding association (p for mediation = 0.540). Although socioeconomic status (subjective social class) was not associated with speeding (β = 0.039, p = 0.177), age was marginally associated with speeding (β = 0.005, p = 0.093). Future studies may consider using a larger sample., Competing Interests: The authors have declared that no competing interests exist.

Interprofessional education (IPE) for medical students is becoming increasingly important, as reflected in the increasing number of medical schools adopting IPE. However, the current status of and barriers to pre-registration IPE implementation in Japanese medical schools remain unknown. The purpose of this study was to clarify the status and barriers of IPE implementation in medical schools in Japan. We conducted a curriculum survey from September to December 2016 of all 81 medical schools in Japan. We mailed the questionnaire and asked the schools' undergraduate education staff to respond. The survey items were the IPE implementation status and barriers to program implementation. Sixty-four of the 81 schools responded (response rate 79.0%), of which 46 (71.9%) had implemented IPE, 42 (89.1%) as compulsory programs. Half of IPE programs were implemented in the first 2 years, while less than 10% were implemented in the latter years of medical programs. As part of the IPE programs, medical students collaborated with a wide range of professional student groups. The most common learning strategy was lectures. However, one-third of IPE programs used didactic lectures without interaction between multi-professional students. The most common perceived major barrier to implementing IPE was adjustment of the academic calendar and schedule (82.8%), followed by insufficient staff numbers (73.4%). Our findings indicate that IPE is being promoted in undergraduate education at medical schools in Japan. IPE programs differed according to the circumstances of each school. Barriers to IPE may be resolved by improving learning methods, introducing group discussions between multi-professional students in lectures or introducing IPE programs using team-based learning. In summary, we demonstrated the current status and barriers of IPE implementation in Japanese medical schools. Our findings will likely lead to the promotion of IPE programs in Japan., Competing Interests: The authors have declared that no competing interests exist.

MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and have been shown to participate in almost every cellular process. Several miRNAs have recently been implicated in glucose metabolism, but the roles of miRNAs in insulin-resistant conditions, such as obesity or type 2 diabetes, are largely unknown. Herein, we focused on miR-222, the expression of which was increased in the livers of high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin, indicating that miR-222 negatively regulates insulin signaling. As per in silico analysis, miR-222 potentially binds to the 3' untranslated region (3' UTR) of the IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct interaction between miR-222 and the 3' UTR of IRS-1 via luciferase assays. Our findings suggest that up-regulation of miR-222 followed by reduction in IRS-1 expression may be a viable mechanism of insulin resistance in the liver.

Mucosal barrier formed by cationic antimicrobial peptides (CAMPs) is believed to be crucial for host protection from pathogenic gut infection. However, some pathogens can develop resistance to the CAMPs to survive in hosts. Salmonella enterica is a common cause of acute diarrhea. During the course of this disease, the pathogen must continuously colonize the gut lumen, which contains CAMPs. However, it is incompletely understood whether the resistance of Salmonella strains to CAMPs contributes to the development of gut infections. PhoPQ two-component system-dependent lipid A modifications confer resistance to CAMPs in S. enterica serovar Typhimurium. Therefore, we introduced mutations into the PhoPQ-regulated genes in an S. Typhimurium strain, obtaining pagP ugtL and pmrA mutant strains. Each mutant strain demonstrated a distinct spectrum of the resistance to CAMPs. Using streptomycin mouse model for Salmonella diarrhea, we show that the pagP ugtL, but not pmrA, mutant strain had a gut colonization defect. Furthermore, the pagP ugtL, but not pmrA, mutant strain had decreased outer membrane integrity and susceptibility to magainin 2, an alpha-helical CAMP. Taken together, the PagP- and UgtL-dependent resistance to CAMPs was demonstrated to contribute to sustained colonization in the gut. This may be due to the robust outer membrane of S. Typhimurium, inducing the resistance to alpha-helical CAMPs such as α-defensins. Our findings indicate that the development of resistance to CAMPs is required for the S. Typhimurium gut infection.

Objectives: To assess the impact of the quantity of resources for breast and cervical cancer screening on the participation rates in screening in clinical settings in municipalities, as well as to clarify whether lack of resources impairs access to cancer screening in Japan., Methods: Of the 1,746 municipalities in 2010, 1,443 (82.6%) and 1,469 (84.1%) were included in the analyses for breast and cervical cancer screening, respectively. In order to estimate the effects of the number of mammography units and of gynecologists on the participation rates in breast and cervical cancer screening in clinical settings, multiple regression analyses were performed using the interaction term for urban municipalities., Results: The average participation rate in screening in clinical settings was 6.01% for breast cancer, and was 8.93% for cervical cancer. The marginal effect of the number of mammography units per 1,000 women was significantly positive in urban municipalities (8.20 percent point). The marginal effect of the number of gynecologists per 1,000 women was significantly positive in all municipalities (2.54 percent point) and rural municipalities (3.68 percent point)., Conclusions: Lack of mammography units in urban areas and of gynecologists particularly in rural areas impaired access to breast and cervical cancer screening. Strategies are required that quickly improve access for the residents and increase their participation rates in cancer screening.

Objective: To investigate the cost-effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan., Methods: The clinical effectiveness and cost-effectiveness of screening and subsequent intervention for AMD were assessed using a Markov model. The Markov model simulation began at the age of 40 years and concluded at the age of 90 years. The first-eye and second-eye combined model assumed an annual state-transition probability, development of prodromal symptoms, choroidal neovascularization (CNV), and reduction in visual acuity. Anti-vascular-endothelial-growth-factor (anti-VEGF) intravitreal injection therapy and photodynamic therapy (PDT) were performed to treat CNV. Intake of supplements was recommended to patients who had prodromal symptoms and unilateral AMD. Data on prevalence, morbidity, transition probability, utility value of each AMD patient, and treatment costs were obtained from published clinical reports., Results: In the base-case analysis, screening for AMD every 5 years, beginning at the age of 50 years, showed a decrease of 41% in the total number of blind patients. The screening program reduced the incidence of blindness more than did the additional intake of supplements. However, the incremental cost-effectiveness ratio (ICER) of screening versus no screening was 27,486,352 Japanese yen (JPY), or 259,942 US dollars (USD) per quality-adjusted life year (QALY). In the sensitivity analysis, prodromal symptom-related factors for AMD had great impacts on the cost-effectiveness of screening. The lowest ICER obtained from the best scenario was 4,913,717 JPY (46,470 USD) per QALY, which was approximately equal to the willingness to pay in Japan., Conclusions: Ophthalmologic screening for AMD in adults is highly effective in reducing the number of patients with blindness but not cost-effective as demonstrated by a Markov model based on clinical data from Japan.

The purpose of this study was to develop quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the analysis of proteins involved in metastasis of breast cancer for diagnosis and determining disease prognosis, as well as to further our understand of metastatic mechanisms. We have previously demonstrated that the protein type XIV collagen may be specifically expressed in metastatic tissues by two dimensional LC-MS/MS. In this study, we developed quantitative LC-MS/MS methods for type XIV collagen. Type XIV collagen was quantified by analyzing 2 peptides generated by digesting type XIV collagen using stable isotope-labeled peptides. The individual concentrations were equivalent between 2 different peptides of type XIV collagen by evaluation of imprecise transitions and using the best transition for the peptide concentration. The results indicated that type XIV collagen is highly expressed in metastatic tissues of patients with massive lymph node involvement compared to non-metastatic tissues. These findings were validated by quantitative real-time RT-PCR. Further studies on type XIV collagen are desired to verify its role as a prognostic factor and diagnosis marker for metastasis.

Objective: Endoscopic gastric cancer is screened in primary care settings, but how much resources are required to deliver this service remains unknown. This study determines how much time and human resources are used for endoscopic gastric cancer and for each component of the procedure., Materials and Methods: Upper endoscopic procedures were prospectively observed using a work sampling technique. This study analyzed data from patients who underwent upper endoscopic gastric cancer screening at primary care clinics that provide this service. The main outcome measurements were time intervals and total time intervals that considered the numbers of simultaneously engaged workers and were calculated as the product of time intervals and the number of workers, and the labor cost of individual components of each procedure., Results: We observed 44 upper endoscopic procedures at four outpatient clinics. Pre-procedure (preparation and pre-medication), procedure (from intubation to extubation) and post-procedure (recovery and cleaning) accounted for 34.1%, 10.6% and 54.4% of the total time, respectively. Of the overall total time intervals (mean: 4453 person-seconds), 29.3%, 14.4% and 55.7% of the total time was devoted to pre-procedure, procedure and post-procedure, respectively. The post-procedure was the most time- and labor-consuming component from the viewpoints of both total time and labor cost., Conclusions: Most of the time taken to complete endoscopic gastric cancer screening is consumed by preparation, pre-medication and post-procedures in which nurses play key roles.

Primordial germ cells (PGCs) arise elsewhere in the embryo and migrate into developing gonadal ridges during embryonic development. In several model animals, formation and migration patterns of PGCs have been studied, and it is known that these patterns vary. Sturgeons (genus Acipenser) have great potential for comparative and evolutionary studies of development. Sturgeons belong to the super class Actinoptergii, and their developmental pattern is similar to that of amphibians, although their phylogenetic position is an out-group to teleost fishes. Here, we reveal an injection technique for sturgeon eggs allowing visualization of germplasm and PGCs. Using this technique, we demonstrate that the PGCs are generated at the vegetal pole of the egg and they migrate on the yolky cell mass toward the gonadal ridge. We also provide evidence showing that PGCs are specified by inheritance of maternally supplied germplasm. Furthermore, we demonstrate that the migratory mechanism is well-conserved between sturgeon and other remotely related teleosts, such as goldfish, by a single PGCs transplantation (SPT) assay. The mode of PGCs specification in sturgeon is similar to that of anurans, but the migration pattern resembles that of teleosts.

Objective: Inequity in physician distribution poses a challenge to many health systems. In Japan, a new postgraduate training program for all new medical graduates was introduced in 2004, and researchers have argued that this program has increased inequalities in physician distribution. We examined the trends in the geographic distribution of pediatricians as well as all physicians from 1996 to 2010 to identify the impact of the launch of the new training program., Methods: The Gini coefficient was calculated using municipalities as the study unit within each prefecture to assess whether there were significant changes in the intra-prefectural distribution of all physicians and pediatricians before and after the launch of the new training program. The effect of the new program was quantified by estimating the difference in the slope in the time trend of the Gini coefficients before and after 2004 using a linear change-point regression design. We categorized 47 prefectures in Japan into two groups: 1) predominantly urban and 2) others by the definition from OECD to conduct stratified analyses by urban-rural status., Results: The trends in physician distribution worsened after 2004 for all physicians (p value<.0001) and pediatricians (p value = 0.0057). For all physicians, the trends worsened after 2004 both in predominantly urban prefectures (p value = 0.0012) and others (p value<0.0001), whereas, for pediatricians, the distribution worsened in others (p value = 0.0343), but not in predominantly urban prefectures (p value =0.0584)., Conclusion: The intra-prefectural distribution of physicians worsened after the launch of the new training program, which may reflect the impact of the new postgraduate program. In pediatrics, changes in the Gini trend differed significantly before and after the launch of the new training program in others, but not in predominantly urban prefectures. Further observation is needed to explore how this difference in trends affects the health status of the child population.

The Echiura, or spoon worms, are a group of marine worms, most of which live in burrows in soft sediments. This annelid-like animal group was once considered as a separate phylum because of the absence of segmentation, although recent molecular analyses have placed it within the annelids. In this study, we elucidate the interfamily relationships of echiuran worms and their evolutionary pattern of feeding mode and sexual dimorphism, by performing molecular phylogenetic analyses using four genes (18S, 28S, H3, and COI) of representatives of all extant echiuran families. Our results suggest that Echiura is monophyletic and comprises two unexpected groups: [Echiuridae+Urechidae+Thalassematidae] and [Bonelliidae+Ikedidae]. This grouping agrees with the presence/absence of marked sexual dimorphism involving dwarf males and the paired/non-paired configuration of the gonoducts (genital sacs). Furthermore, the data supports the sister group relationship of Echiuridae and Urechidae. These two families share the character of having anal chaetae rings around the posterior trunk as a synapomorphy. The analyses also suggest that deposit feeding is a basal feeding mode in echiurans and that filter feeding originated once in the common ancestor of Urechidae. Overall, our results contradict the currently accepted order-level classification, especially in that Echiuroinea is polyphyletic, and provide novel insights into the evolution of echiuran worms.

Community structure is a universal and significant feature of many complex networks in biology, society, and economics. Community structure has also been revealed in human brain structural and functional networks in previous studies. However, communities overlap and share many edges and nodes. Uncovering the overlapping community structure of complex networks remains largely unknown in human brain networks. Here, using regional gray matter volume, we investigated the structural brain network among 90 brain regions (according to a predefined anatomical atlas) in 462 young, healthy individuals. Overlapped nodes between communities were defined by assuming that nodes (brain regions) can belong to more than one community. We demonstrated that 90 brain regions were organized into 5 overlapping communities associated with several well-known brain systems, such as the auditory/language, visuospatial, emotion, decision-making, social, control of action, memory/learning, and visual systems. The overlapped nodes were mostly involved in an inferior-posterior pattern and were primarily related to auditory and visual perception. The overlapped nodes were mainly attributed to brain regions with higher node degrees and nodal efficiency and played a pivotal role in the flow of information through the structural brain network. Our results revealed fuzzy boundaries between communities by identifying overlapped nodes and provided new insights into the understanding of the relationship between the structure and function of the human brain. This study provides the first report of the overlapping community structure of the structural network of the human brain.

To determine the relationship between age and gray matter structure and how interactions between gender and hemisphere impact this relationship, we examined correlations between global or regional gray matter volume and age, including interactions of gender and hemisphere, using a general linear model with voxel-based and region-of-interest analyses. Brain magnetic resonance images were collected from 1460 healthy individuals aged 20-69 years; the images were linearly normalized and segmented and restored to native space for analysis of global gray matter volume. Linearly normalized images were then non-linearly normalized and smoothed for analysis of regional gray matter volume. Analysis of global gray matter volume revealed a significant negative correlation between gray matter ratio (gray matter volume divided by intracranial volume) and age in both genders, and a significant interaction effect of age × gender on the gray matter ratio. In analyzing regional gray matter volume, the gray matter volume of all regions showed significant main effects of age, and most regions, with the exception of several including the inferior parietal lobule, showed a significant age × gender interaction. Additionally, the inferior temporal gyrus showed a significant age × gender × hemisphere interaction. No regional volumes showed significant age × hemisphere interactions. Our study may contribute to clarifying the mechanism(s) of normal brain aging in each brain region.

Expression of Hox genes is tightly regulated in spatial and temporal domains. Evx2 is located next to Hoxd13 within 8 kb on the opposite DNA strand. Early in development, the pattern of Hoxd13 expression resembles that of Evx2 in limb and genital buds. After 10 dpc, however, Evx2 begins to be expressed in CNS as well. We analyzed the region responsible for these differences using ES cell techniques, and found that the intergenic region between Evx2 and Hoxd13 behaves as a boundary element that functions differentially in space and time, specifically in the development of limbs, genital bud, and brain. This boundary element comprises a large sequence spanning several kilobases that can be divided into at least two units: a constitutive boundary element, which blocks transcription regulatory influences from the chromosomal environment, and a regulatory element, which controls the function of the constitutive boundary element in time and space.