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Background: Iron deficiency is the leading cause of anaemia worldwide and is increasingly treated with intravenous (IV) iron therapy. Staining from IV iron therapy is a rare but significant and preventable adverse event. To mitigate patient harm, a health-service-wide quality improvement project was implemented. This study aimed to determine the real-world impact of a quality improvement project on IV iron staining incidents and preventability., Methods: A retrospective chart audit was undertaken for all IV iron staining episodes reported in a directorate-wide clinical incident reporting database (RiskMan) between 2016 and 2022. Incidence rates of IV iron staining, preventability, and stain severity were compared pre- and post-implementation of a standardized IV iron procedure., Results: Over 7 years, 103 IV iron stains were identified, resulting in a staining rate of 0.31 stains per 100 infusions (pre 0.27% and post 0.34%, P = .25). Implementation of the standardized IV iron procedure resulted in improvements in pharmacist review of the medication order (61.8% versus 89.7%, P < .01), use of the statewide IV iron infusion consent form (27.3% versus 76.9%, P < .01), and appropriate cannula site (14.3% versus 52.5%, P < .01). Smaller stain sizes were associated with cessation of the infusion at identification of extravasation (312 cm2 versus 35 cm2) (P = .04). Preventability was assigned to 86% of stains., Conclusion: The incidence rate of IV iron staining in a real-world clinical setting is 0.31%. There was increased compliance with several best practice principles and 86% of stains were preventable. Early identification and intervention of potential staining incidents results in smaller iron stains for patients. Quality improvement tools developed for this project can contribute to patient outcomes internationally., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp + neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp + neurons, neurons expressing nitric oxide synthase 1 (Nos1 + neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1 + neurons also project to areas that control wide forebrain activity. Ablating Crhbp + neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to identify effective initial conservative treatment strategies for patients with temporomandibular joint disorders (TMD)., Study Selection: RCTs comparing treatment options for TMD published between January 2000 and July 2021 were retrieved from the databases of PubMed and Embase via a comprehensive electronic search. Patients diagnosed with myalgia (muscle pain) or arthralgia (joint pain) according to pain-related Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were eligible for inclusion. Twelve treatment options and a placebo were included in the mutual comparisons. The risk of bias was assessed using Risk of Bias 2.0. Forest plots of direct comparisons between individual studies were created using MetaInsight. NMA was performed using R statistical software (netmeta)., Results: Twenty-four RCTs involving 1336 patients assessing pain and 12 RCTs involving 614 patients assessing maximal mouth opening were identified. Low-level laser therapy (standard mean difference [SMD]: -2.12, 95% confidence interval [CI]: -3.18, -1.06), self-exercise (SMD: -1.51, 95% CI: -2.82, -0.2), and stabilization splints (SMD: -1.16, 95% CI: -2.02, -0.29) were effective in improving pain; however, the certainty of evidence was very low. Self-exercise (SMD: 0.71, 95% CI: -0.58, 2.01), stabilization splints (SMD: 0.65, 95% CI: -0.09, 1.39), and low-level laser therapy (SMD: 0.63, 95% CI: -0.34, 1.6) were effective in improving maximal mouth opening; however, the certainty of evidence was very low., Conclusions: Stabilization splints, self-exercise, and low-level laser therapy may be effective in the initial treatment of TMD.

Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An aging nursing workforce requires addressing shortages due to retirement. This nationwide descriptive cross-sectional study in Japan clarified the employment status of older nursing staff aged ≥ 55 years by facility type during January-March 2022. Questionnaires were sent to 8,000 nursing directors, with 1,658 valid responses (response rate: 20.7%). Descriptive statistics and Kruskal-Wallis or χ2 tests analyzed inter-facility differences. A violin plot depicted the proportion of older nursing staff across facilities by age group, and generalized estimating equation (GEE) models examined associated factors at the facility level. Older nursing staff's distribution differed significantly across age groups ( p < 0.01), from 0% to 100% within the same facility type. Some facilities had high percentages of staff working beyond retirement age. GEE results showed higher percentages of full-time employees and nurses were negatively associated with the percentage of older nursing staff across most facility types ( p < 0.05). For those aged ≥ 65 years, the total population was positively associated with employment in bedded clinics (coef. = 0.07, 95% CI: 0.01 to 0.14, p = 0.03), but negatively associated with the total population (coef. = -0.06, 95% CI: -0.10 to -0.01, p = 0.02) and percentage of the population aged ≥ 65 (coef. = -0.76, 95% CI: -1.43 to -0.08, p = 0.03) in long-term care insurance facilities. Working conditions and environments should be improvement to potentially retain older nursing staff. Job seekers should be matched with managers' needs in facilities with a higher proportion of older nursing staff to ensure a sustainable workforce., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Objective　This scoping review aimed to provide an overview of collaborative practices for children with medical complexities and their families by life stage.Methods　This scoping review was conducted based on the JBI scoping review manual using the PubMed, CINAHL, and Medical Journal databases. Search terms included "collaboration," "intersectoral collaboration," "children with medical complexity," and "children with special healthcare needs," whereas control words included "children with special healthcare needs," "children with medical care," "children with severe mental and physical disabilities," and "children with severe mental and physical disabilities." The inclusion criteria were articles in Japan that reported on practices for children (aged 0-18 years) with medical care needs and collaboration among other multiple professions, research articles, excluding review and protocol articles, and English or Japanese articles. For the analysis, collaboration-related practices were extracted from selected papers, categorized based on similarities in content, and further summarized according to the life stage. Three researchers discussed the selection of papers, data extraction, and analysis until a consensus was reached.Results　The analysis included 30 papers (27 Japanese and three English papers). Regarding publication year, 14 papers were published within the last 3 years. Additionally, 19 case and 26 practice reports and 11 studies (quantitative research; one, qualitative research; 10) were published by professionals. Regarding collaborative practices, 160 cases were extracted and classified into nine. In "discharge support," practices in all subcategories were reported for preschoolers, whereas only two of the five subcategories were reported for school-aged children. Contrastingly, in the "maintenance phase in preschool, daycare, and school," preschoolers reported practices in two of the seven subcategories. Additionally, various professionals from the fields of medicine, welfare, education, and administration were involved in the collaboration.Conclusion　There were differences in the reporting of collaborative practices at each life stage. Although numerous professionals were involved, reports of collaborative practices among them were unevenly distributed. Eventually, it will be necessary to investigate the nature of collaborative practices among various professionals, focusing on children and their families.

Aim: We determined the number of care transitions in the year before death among older adults requiring long-term care (LTC) and those receiving public LTC insurance (LTCI) services in Japan, along with care transition pathways and factors associated with the number of care transitions., Methods: This study used data from the Japanese LTCI claims, which store national information on certification of needed LTC and LTCI claims data. Services received in the year before death were classified as in-home, facility, mixture of in-home and facility, and not using LTCI services. The transition count is presented, and Sankey diagrams are produced to visualize care transition pathways. We used a multivariable analysis to identify factors associated with the number of care transitions., Results: Of the participants, 276 896 (65.2%) experienced at least one transition in LTCI care settings in the year before death. Further, 72.0% of those requiring mild LTC underwent one or more transitions. Participants who were 75-84 years old (vs. 65-74 years old), male, without medical care needs, with symptoms of dementia, and with changes in LTC needs in the year before death were more likely to require care transitions. Moreover, participants with higher baseline LTC needs were less likely to require transitions., Conclusion: Over half the participants requiring LTC underwent one or more care transitions in the year before death. Policy deliberations regarding enhancing care under the LTCI system at the end of life and optimizing care transitions are necessary. Geriatr Gerontol Int 2024; ••: ••-••., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice ( Oryza sativa L.) and to analyze the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in the germination percentage and RNA integrity number (RIN) after long-term storage or CDT. The RIN value was obtained by the electrophoresis of the total RNA extracted from the seed embryos. Seeds of "Vandaran ( indica )", "Tupa 729 ( japonica )", and "Badari Dhan ( indica )" consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions regardless of the harvest year. A strong correlation (R 2 = 0.93) was observed between the germination percentages and RIN values of the seeds after the long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials including both japonica and indica cultivars for improving rice seed longevity.

Debranching thoracic endovascular aortic repair may disturb the implantation of a cardiac implantable electronic device in the anterior thoracic region. In case 1, the bypass graft between the right axillary artery, left axillary artery, and left common carotid artery disturbed pacemaker implantation from the left anterior thoracic region. Therefore, right-sided implantation was selected. By contrast, in case 2, the bypass graft between axillary arteries in the anterior thoracic region was visible on fluoroscopy, and we performed conventional left-sided pacemaker implantation with extra-thoracic puncture. The pacemaker implantations were successful in both cases. The implantation strategies were affected by the number of debranched arteries and visibility of the bypass graft., (© 2023 Wiley Periodicals LLC.)

Background: Left ventricular (LV) structural and functional changes have been reported in patients with aortic stenosis (AS) who have undergone transcatheter aortic valve implantation (TAVI); however, the relationship between change in LV structure and systolic function and tissue characteristics assessed via cardiovascular magnetic resonance imaging (CMRI) post-TAVI has been not fully elucidated. This study aimed to investigate this relationship in patients with severe AS who underwent TAVI and CMRI., Methods: In this retrospective study, 65 patients who underwent TAVI and CMRI at the 6-month follow-up were analyzed. The relationship between percent changes in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass (LVM) (⊿LVEDV, ⊿LVESV, ⊿LVEF, and ⊿LVM) and those in the native T1 value (⊿native T1) was analyzed using a correlation analysis. Moreover, extracellular volume fraction (ECV) value changes were analyzed., Results: The ⊿native T1 significantly decreased from 1292.8 (1269.9-1318.4) ms at pre-TAVI to 1282.3 (1262.6-1310.2) ms at the 6-month follow-up (P = 0.022). A significant positive correlation between ⊿LVEDV, ⊿LVESV, and ⊿LVM and ⊿native T1 (r = 0.351, P = 0.004; r = 0.339, P = 0.006; r = 0.261, P = 0.035, respectively) and a tendency toward a negative correlation between ⊿LVEF and ⊿native T1 (r = -0.237, P = 0.058) were observed. The ECV value increased significantly from 26.7 % (25.3-28.3) to 28.2 % (25.7-30.5) (P = 0.002)., Conclusions: The decrease in native T1 might be associated with LV reverse remodeling. Evaluating structural and functional changes using CMRI may be useful for patient management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The relationship between subclinical atrial fibrillation (SCAF) and left pulmonary vein anatomy is unknown. This study sought to investigate whether left pulmonary vein trunk predict the development of SCAF in patients with cardiac implantable electronic device (CIED). We also examined the relationship between the duration of SCAF and left pulmonary vein trunk. We retrospectively enrolled 162 patients who underwent implantation of dual-chamber CIEDs and follow-up by remote monitoring system. Computed tomography was used to measure the length of the left pulmonary vein. During median follow up of 2.7 years, the episodes of > 6 min and > 24 h SCAF were observed in 61 (37.7%) and 24 (14.8%) patients, respectively. The diagnosis of sinus node disease (HR: 3.66 [2.06-6.52], P < 0.01 and HR: 2.68 [1.09-6.62], P = 0.04) and left atrial diameter (HR: 1.04 [1.00-1.07], P = 0.04 and HR: 1.05 [1.00-1.10], P = 0.04) were independent predictors for > 6 min and > 24 h SCAF, respectively. Length of the left pulmonary vein trunk was an independent predictor for > 6 min SCAF (HR: 1.06 [1.02-1.10], P < 0.01), but not for > 24 h SCAF (P = 0.06). Sinus node disease, size of the left atrium and length of the left pulmonary vein trunk were related to SCAF. The left pulmonary vein trunk might especially contribute as a trigger rather than as a driver of development of atrial fibrillation., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Cancer was ranked as the second leading cause of global mortality in 2019, with an increasing incidence. An adequate workforce of healthcare professionals with special skills and knowledge in cancer care is vital for addressing the disparities in cancer prognosis. This study aimed to elucidate the trends in the advanced practice nursing workforce (APNW) in cancer care, which included certified nurse specialists (CNSs) and certified nurses (CNs) in each prefecture of Japan from the system's inception to the present. Further, it sought to analyze the regional disparities and compare these trends with other healthcare resources to identify contributing factors associated with the APNW in cancer care in each prefecture., Methods: We performed a panel data analysis using publicly available data on the APNW in cancer care in each prefecture of Japan from 1996 to 2022. Gini coefficients were calculated to examine the trends in geographic equality. Univariate and multivariable fixed effect panel data regression models were used to examine regional factors associated with an APNW in cancer care., Results: From 1996 to 2012, the APNW in cancer care increased from four to 6982 staff, while their Gini coefficients decreased from 0.79 to 0.43. However, from 2012 to 2022, the Gini coefficients decreased slightly from 0.43 to 0.41. The coefficient value was comparable to that for the disparity between hospital doctors (0.43) but more pronounced compared to those for other medical resources, such as hospitals (0.34), hospital nurses (0.37), and designated cancer care hospitals (0.29). The APNW in cancer care in each prefecture was significantly associated with a higher number of designed cancer care hospitals in the previous year (see first quartile, the coefficient for second quartile: 0.31, 95% confidence interval (CI) 0.21-0.40), and a fewer number of hospital doctors (- 1.89, 95%CI - 2.70 to - 1.09)., Conclusions: The size of the APNW in cancer care has increased since the system was established in 1996 up till 2022. With the increase in numbers, geographic inequality narrowed until 2012 and has since then remained stagnant., (© 2024. The Author(s).)

Objectives: In April 2012, the Japanese government launched a new nursing service called the nursing small-scale multifunctional home care (NSMHC) to meet the nursing care demands of individuals with moderate-to-severe activities of daily living (ADLs) dysfunction and who require medical care, thereby allowing them to continue living in the community. We aimed to preliminarily analyse the characteristics of first-time users of NSMHC service., Design: This pooled cross-sectional study used the Japanese long-term care insurance (LTCI) claims data from the users' first use of NSMHC (from April 2012 to December 2019)., Setting: NSMHC includes nursing home visits, home care, daycare, overnight stays and medical treatment., Participants: The study population included LTCI beneficiaries who received their first long-term care requirement certification in Japan from April 2012 onwards, died between April 2012 and December 2019, and used any LTCI service at least once., Results: Among the 836 563 individuals who used any LTCI service at least once, 3957 (0.47%) used NSMHC. We analysed 3634 individuals without any missing data regarding long-term care requirement certification. Most individuals were aged 80 years or older, with 64.3% requiring care level 3 or above, indicating complete assistance with ADLs. Regarding ADLs in individuals with dementia, 70.6% were at level 2 or below, indicating they can live almost independently even with dementia. A large proportion of NSMHC users availed the service approximately 6 months before death, with no prior use of any LTCI services; they continued using the service for around 4 months, although some people continued to use NSMHC until their month of death., Conclusions: Using individual data on nationwide LTCI, we described the characteristics of first-time users of NSMHC among those who died within 7.5 years from the first certification of care needs. Further studies are needed to investigate the effect of NSMHC use on user outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The long-term impact of Kawasaki disease on coronary arteries in vivo is unclear., Objectives: The purpose of this study was to investigate coronary arteries in the late convalescent phase, we followed patients with Kawasaki disease who developed coronary artery aneurysms (CAAs)., Methods: We followed 24 patients and used optical coherence tomography at a median of 16.6 years after the onset of Kawasaki disease., Results: Of 72 coronary arteries, optical coherence tomography was performed on 61 arteries: 17 with a persistent CAA, 29 with a regressed CAA, and 15 without a CAA. Between-group comparison was performed by chi-square or Fisher's exact test, and intimal thickening (17 vs 29 vs 15, all 100%, P  = NA) and medial disruption (17 [100%] vs 29 [100%] vs 14 [93%], P  = 0.25) were commonly observed in the investigated arteries. Advanced features of atherosclerosis were more frequently seen in arteries with persistent CAAs than in those with regressed CAAs and in those without CAAs: calcification (12 [71%] vs 5 [17%] vs 1 [7%], P  < 0.001), microvessels (12 [71%] vs 10 [35%] vs 4 [27%], P  = 0.020), cholesterol crystals (6 [35%] vs 2 [7%] vs 0 [0%], P  = 0.009), macrophage accumulation (11 [65%] vs 4 [14%] vs 4 [27%], P  = 0.002), and layered plaque (8 [47%] vs 11 [38%] vs 0 [0%], P  = 0.004)., Conclusions: Long after onset of Kawasaki disease, all arteries showed pathological changes. Arteries with persistent CAAs had more advanced features of atherosclerosis than those with regressed CAAs and those without CAAs., Competing Interests: This research was supported by 10.13039/100009619AMED under Grant Number JP22ek0109467. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

A male in his late 30s was found dead in his home. He was diagnosed with human immunodeficiency virus (HIV) about six years prior. The HIV infection was well controlled before his death. He was 166 cm in height and 75 kg in weight. Aside from discoloration of the skin on the right lower patellar, there were no obvious injuries. His brain weighed 1456 g. A cut surface of the brain revealed left thalamic hemorrhage. Histologically, infiltration of phagocytic cells was observed in the bleeding site. Thalamic hemorrhage was considered to be his cause of death in this case. Due to the effects of anti-HIV therapy, the mortality rate from HIV infection has decreased and the causes of death of HIV-infected persons have changed. HIV-infected persons have been suggested to be associated with cerebrovascular disease, especially juvenile ischemic stroke. Patients with acquired immunodeficiency syndrome (AIDS) have an increased risk of cerebrovascular disease. Possible mechanisms of cerebrovascular disease in HIV-infected individuals include coagulopathy, secondary effects of embolism and central nervous system infection, and direct vascular disease due to HIV. At the time of autopsy, his post-mortem interval was estimated to be approximately two weeks. Therefore, it was difficult to clarify histologically the cerebrovascular disorder that caused his cerebral hemorrhage. In recent years, anti-HIV therapy has reduced the number of AIDS-related deaths, but deaths in HIV-infected people from cardiovascular disease are increasing. This case is considered to be a valuable forensic autopsy case of an HIV-infected patient who actually died due to cerebral hemorrhage in Japan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: Although there are many reports of temperature being associated with the onset of acute coronary syndrome (ACS), few studies have examined differences in ACS due to climatic differences between Japan and Thailand. The aim of this joint Japan-Thailand study was to compare patients with myocardial infarction in Japanese and Thai hospitals in different climates. Methods and Results: We estimated the climate data in 2021 for the Wakayama Prefecture and Chonburi Province, two medium-sized cities in Japan and Thailand, respectively, and ACS patients who were treated at the Wakayama Medical University (WMU) and Burapha University Hospital (BUH), the two main hospitals in these provinces (ACS patient numbers: WMU, n=177; BUH, n=93), respectively. In the Chonburi Province, although the average temperature was above 25℃, the number of ACS cases in BUH varied up to threefold between months (minimum: July, 4 cases; maximum: October, 14 cases). In Japan and Thailand, there was a mild to moderate negative correlation between temperature-atmospheric pressure at the onset of ACS, but different patterns for temperature-humidity (temperature-atmospheric pressure, temperature-humidity, and atmospheric pressure-humidity: correlation index; r=-0.561, 0.196, and -0.296 in WMU vs. r=-0.356, -0.606, and -0.502 in BUH). Conclusions: The present study suggests that other climatic conditions and factors, not just temperature, might be involved in the mechanism of ACS., Competing Interests: All authors report that they have no relationships relevant to the content of this paper., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Competing Interests: The authors declare no conflicts of interest.

The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2β (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development and mice in which neuronal Tfap2b was specifically deleted postnatally. Both types of mice exhibited reduced NREM sleep, but the nervous system-specific deletion of Tfap2b resulted in more severe sleep phenotypes accompanied by defective light entrainment of the circadian clock and stereotypic jumping behavior. These findings indicate that TFAP2B in postnatal neurons functions at least partly in sleep regulation and imply that TFAP2B also functions either at earlier stages or in additional cell types within the nervous system., (© 2024. The Author(s).)

Background: Bone morphogenetic protein-2 ( bmp-2 ) has a high potential to induce bone tissue formation in skeletal muscles. We developed a bone induction system in skeletal muscles using the bmp-2 gene through in vivo electroporation. Natural bone tissues with skeletal muscles can be considered potential candidates for biomaterials. However, our previous system using plate-type electrodes did not achieve a 100% success rate in inducing bone tissues in skeletal muscles. In this study, we aimed to enhance the efficiency of bone tissue formation in skeletal muscles by using a non-viral bmp-2 gene expression plasmid vector (pCAGGS- bmp-2 ) and needle-type electrodes., Methods: We injected the bmp-2 gene with pCAGGS- bmp-2 into the skeletal muscles of rats' legs and immediately placed needle-type electrodes there. Skeletal tissues were then observed on the 21st day after gene transfer using soft X-ray and histological analyses., Results: The use of needle-type electrodes resulted in a 100% success rate in inducing bone tissues in skeletal muscles. In contrast, the plate-type electrodes only exhibited a 33% success rate. Thus, needle-type electrodes can be more efficient and reliable for transferring the bmp-2 gene to skeletal muscles, making them potential biomaterials for repairing bone defects.

Background: We encountered a urine sample suspected of being mixed with tea, submitted by a suspect attempting to camouflage illegal drugs. Although urine should turn reddish-pink during a urea test with p-Dimethylaminocinnamaldehyde (DAC), this suspect's sample exhibited a blue coloration when tested with DAC., Aim: Our aim was to examine the influence and mechanism of green tea on various urine identification tests., Results: Our examination revealed that DAC forms a compound with the urea in urine, resulting in a reddish pink coloration with a molecular weight of 217. However, it has been reported that DAC binds to polyphenols such as catechin. In the case of catechin, DAC binds to the C8 position, forming a compound that exhibits the highest absorption at 640 nm and appears blue. we investigated the effect of urine from volunteers who had consumed a large amount of catechin on the urea test with DAC. Additionally, we carried out quantitative analysis of catechin in urine by LC-MS/MS after enzymatic treatment with β-glucuronidase. The concentration of urinary excreted catechin reached its peak approximately 3 to 4 h after ingestion. During the DAC test, urine samples collected 3 to 4 h after catechin ingestion displayed a bluish pink color, but not the blue color observed in the original suspect sample., Conclusion: This study investigated the impact of catechin on urine tests, revealing that a blue color in the DAC test indicates a high likelihood of camouflage by the suspect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Studies have indicated that higher numbers of nurses regarding staffing ensure patient safety and a better practice environment. Using citation analysis, this study visualizes the landscape of nurse staffing research over the last two decades to show the overall publication trends, major contributors, and main research topics. We extracted bibliometric information from PubMed from January 2000 to September 2022. After clustering the network, we analyzed each cluster's characteristics by keyword. A total of 2167 papers were considered for analysis, and 14 clusters were created. The analysis showed that the number of papers published per year has been increasing. Researchers from the US, the UK, Canada, Australia, and Belgium have led this field. As the main clusters in nurse staffing research during the past two decades, the following five research settings were identified: nurse outcome and patient outcome research in acute care hospitals, nurse staffing mandate evaluation research, nursing home research, and school nurse research. The first three clusters accounted for more than 80% of the total number of published papers, and this ratio has not changed in the past 20 years. To further develop nurse staffing research globally, evidence from other geographic areas, such as African and Asian countries, and from long-term care or community settings is necessary.

A generic level of chromatin organization generated by the interplay between cohesin and CTCF suffices to limit promiscuous interactions between regulatory elements, but a lineage-specific chromatin assembly that supersedes these constraints is required to configure the genome to guide gene expression changes that drive faithful lineage progression. Loss-of-function approaches in B cell precursors show that IKAROS assembles interactions across megabase distances in preparation for lymphoid development. Interactions emanating from IKAROS-bound enhancers override CTCF-imposed boundaries to assemble lineage-specific regulatory units built on a backbone of smaller invariant topological domains. Gain of function in epithelial cells confirms IKAROS' ability to reconfigure chromatin architecture at multiple scales. Although the compaction of the Igκ locus required for genome editing represents a function of IKAROS unique to lymphocytes, the more general function to preconfigure the genome to support lineage-specific gene expression and suppress activation of extra-lineage genes provides a paradigm for lineage restriction., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Introduction: Insufficient nutrient intake is a strong independent predictor of mortality in elderly patients with heart failure. However, it is unclear to what extent energy intake affects their prognosis. This study investigated the association between patient outcomes and actual measured energy intake in elderly patients (≥65 years) with heart failure., Methods: This study enrolled 139 elderly patients who were hospitalized with worsening heart failure at Shingu Municipal Medical Center, Shingu, Japan, between May 2017 and April 2018. Energy intake was evaluated for three days (from three days prior to the day of discharge until the day of discharge). Based on basal energy expenditure calculated using the Harris-Benedict equation, the patients were classified into a low-energy group ( n = 38) and a high-energy group ( n = 101). We assessed the prognosis in terms of both all-cause mortality and readmission due to worsening heart failure as a primary outcome., Results: Compared to the patients in the high-energy group, the patients in the low-energy group were predominantly female, less frequently had smoking habits and ischemic heart diseases, and had a higher left ventricular ejection fraction. The low-energy group had higher mortality than the high-energy group ( p = 0.028), although the two groups showed equivalent event rates of the primary outcome ( p = 0.569)., Conclusion: Calculations based on the Harris-Benedict equation revealed no significant difference in the primary outcome between the two groups, with a secondary outcome that showed worse mortality in the low-energy group. Given this result, energy requirement-based assessments using the Harris-Benedict equation might help in the management of elderly heart failure patients in terms of improved life outcomes.

Background: Cardiac amyloidosis (CA) progresses rapidly with a poor prognosis. Therefore, methods for early diagnosis that are easily accessible in any hospital, are required. We hypothesized that based on the pathology of CA, morphological left ventricular hypertrophy (LVH) without electrical augmentation, namely paradoxical LVH, could be used to diagnose CA. This study aimed to investigate whether paradoxical LVH has diagnostic significance in identifying CA in patients with LVH., Methods: Patients who presented with left ventricular (LV) wall thickness ≥ 12 mm on cardiac magnetic resonance (CMR) were enrolled from a multicentre CMR registry. Paradoxical LVH was defined as a LV wall thickness ≥ 12 mm on CMR, SV1 + RV5 < 3.5 mV, and a lack of secondary ST-T abnormalities. The diagnostic significance of paradoxical LVH in identifying CA was assessed., Results: Of the 110 patients enrolled, 30 (27 %) were diagnosed with CA and 80 (73 %) with a non-CA aetiology. The CA group demonstrated paradoxical LVH more frequently than the non-CA group (80 % vs. 16 %, P  < 0.001). It was an independent predictor for detecting CA in patients with LVH (odds ratio: 33.44, 95 % confidence interval: 8.325-134.3, P  < 0.001). The sensitivity, specificity, positive predict value, negative predict value and accuracy of paradoxical LVH for CA detection were 80 %, 84 %, 65 %, 92 % and 83 %, respectively., Conclusions: Paradoxical LVH can be used for identifying CA in patients with LVH. Our findings could contribute to the early diagnosis of CA, even in non-specialized hospitals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: Atrial fibrillation (AF) frequently occurs after pulmonary resection and is commonly referred to as postoperative atrial fibrillation (POAF). This study explored whether or not POAF is related to the recurrence of AF in the chronic phase., Methods: A total of 1311 consecutive patients without a history of AF who underwent lung resection based on a diagnosis of lung tumor were retrospectively analyzed., Results: POAF occurred in 46 patients (3.5%), and a logistic regression analysis revealed that the age (p < 0.05), history of hyperthyroidism (p < 0.05), and major lung resection (p < 0.05) were independent predictors of POAF. AF events in the chronic phase were observed in 15 (32.6%) and 45 (3.6%) patients with and without POAF, respectively. A Cox regression analysis revealed that POAF was the only independent predictor of AF development in the chronic phase (p < 0.01). The Kaplan-Meier curve and log-rank test revealed that the cumulative incidence of AF in the chronic phase was significantly higher in patients with POAF than in those without POAF (p < 0.01)., Conclusion: POAF was an independent predictor for AF in the chronic phase after lung resection. Further investigations including cases of catheter ablation and optimal medical therapy for patients with POAF after lung resection are needed., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: This study aimed to investigate the relationship between postoperative atrial fibrillation (POAF) after esophagectomy and pre-existing cardiac substrate., Methods: We retrospectively analyzed 212 consecutive patients from between July 2010 and December 2022 who were scheduled to undergo esophagectomy for esophageal cancer without previous history of atrial fibrillation. All the patients underwent both echocardiography and contrast-enhanced multi-detector computed tomography (MDCT)., Results: POAF occurred in 49 patients (23.1%). Multivariable logistic analysis demonstrated that independent predictors for POAF were age [OR; 1.06 (1.01-1.10), P < 0.01), three-field lymph node dissection [OR; 2.55 (1.25-5.23), P < 0.01), left atrial dilatation (> 35 mm) assessment by echocardiography [OR; 3.05 (1.49-6.25), P < 0.01) and common left pulmonary vein [OR; 3.03 (1.44-6.39), P < 0.01). The correlation coefficient was high for left atrial dimensions assessed by echocardiography and MDCT (r = 0.91, P < 0.01). Combination of left atrial dilatation by echocardiography and common left pulmonary vein had high odds ratio [OR; 8.10 (2.62-25.96), P < 0.01). Instead of echocardiographic assessment, combination of left atrial enlargement (> 35 mm) assessed by MDCT and common left pulmonary vein also showed high odds ratio for POAF [OR; 11.23 [2.19-57.63], P < 0.01)., Conclusion: Incidence of POAF after esophagectomy was related to both left atrial enlargement and common left pulmonary vein assessed by preoperative MDCT. Additional analysis of atrial size and pulmonary vein variation would facilitate preoperative assessment of the risk of POAF, but future studies must ascertain therapeutic strategy., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Aims: This study aimed to clarify the relationships among tooth loss, periodontal condition, and subclinical atherosclerosis from the aspect of intensity, extent, and duration of inflammation., Methods: This cross-sectional study included 9,778 people from the Nagahama Study, a large-scale, general population-based study conducted in Japan. The number of teeth and periodontal status, including the attachment level (AL) and pocket depth (PD) of representative teeth from six regions, were evaluated by dentists. The maximum intima-media thickness (IMT) of the common carotid artery was used as an index of atherosclerosis., Results: In the multivariate analysis adjusted for conventional risk factors, a large number of missing teeth (＜9 remaining teeth), which related to long-lasting inflammation indicative of the highest stage of periodontitis, was identified as an independent determinant of IMT in a general population (coefficient: 0.042; 95% confidence interval [CI]: 0.016 to 0.068). The presence of two or more regions with an AL ≥4 mm, which is indicative of the progressing, long-lasting stages of periodontal inflammation, was also independently associated with IMT (coefficient: 0.016; 95% CI: 0.004 to 0.028). On the contrary, PD, a measure of the early and reversible phases of periodontal inflammation, and loss of AL in the group without tooth loss were not significantly associated with IMT, because of the limited degree of accumulated periodontitis., Conclusion: The present results suggest that the association between periodontitis and atherosclerosis depends on the inflammation intensity, extent, and duration.

Radical cystectomy is a gold-standard treatment for muscle-invasive bladder cancer. We recently introduced robot-assisted radical cystectomy (RARC) with perioperative enhanced recovery after surgery (ERAS). The medical records of patients with bladder cancer who underwent open radical cystectomy (ORC) or RARC/ERAS at NTT Medical Center Tokyo were retrospectively reviewed to compare the surgical outcomes, hospital stay, and medical costs between groups. Multidisciplinary full ERAS items were provided for the RARC/ERAS group. The median estimated blood losses in the ORC and RARC/ERAS groups were 650 and 100 mL, and the median operative times were 312 and 445 min, respectively. In addition, the median times to liquid food intake in these groups were 6 and 0 days, the median times to first flatus and first defecation were 2 and 1 day, and 3 and 1.5 days, respectively. The rates of postoperative ileus in the ORC and RARC/ERAS groups were 27.5% and 4.5%, and the median postoperative hospital stays was 26.5 and 12 days, respectively. Medical costs excluding surgery were significantly lower in the RARC/ERAS group. In conclusion, RARC/ERAS represents a safe treatment option for muscle-invasive bladder cancer with decreased perioperative complications and lower medical costs., (© 2023. Springer Nature Limited.)

Phenylacetylglutamine (PAG) is a metabolite that is excreted in human urine. Phenylalanine is metabolized to phenylacetic acid, which is then amide-bonded to glutamine to form PAG. We are currently studying PAG as a urinary biomarker in forensic autopsy cases., Materials and Methods: Urine samples were collected from 188 forensic autopsy cases and the urinary PAG concentration was analyzed quantitatively using GC-MS. Urinary creatinine (Cr) concentration was also analyzed by GC-MS. For statistical analysis, the JMP Pro 15.0.0 software program was used. The relationship between urine PAG/Cr (the ratio of each concentration), sex, age, postmortem interval (PMI), survival duration, and cause of death was statistically analyzed., Results and Discussion: The median (range) of PAG/Cr was 0.12 (0.002-3.26). The PAG/Cr ratio showed no significant relationship to sex or survival duration. Regarding the cause of death, traumatic brain injuries had a significantly higher ratio than intoxication (p=0.023). Cerebrovascular disease, such as cerebral hemorrhage and subarachnoid hemorrhage, did not differ significantly from any cause of death group. However, when traumatic brain injuries and cerebrovascular accidents are combined as one cause of death group, the PAG/Cr value of CNS damages was significantly higher than that of intoxication (p=0.062)., Conclusion: Urinary PAG/Cr might be a biomarker not only for traumatic brain injuries but also for antemortem CNS damages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Upregulation of Toll-like receptor 4 (TLR-4) is associated with coronary plaque vulnerability assessed by coronary computed tomography angiography (CCTA). Computed tomography-adapted Leaman score (CT-LeSc) is an independent long-term predictor of cardiac events. The relationship between the TLR-4 expression of CD14 ++ CD16 + monocytes and future cardiac events is unknown. We investigated this relationship using CT-LeSc in patients with coronary artery disease (CAD)., Methods: We analyzed 61 patients with CAD who underwent CCTA. Three monocyte subsets (CD14 ++ CD16 - , CD14 ++ CD16 + , and CD14 + CD16 + ) and the expression of TLR-4 were measured by flow cytometry. We divided the patients into two groups according to the best cutoff value of the TLR-4 expression on CD14 + CD16 + which could predict future cardiac events., Results: CT-LeSc was significantly greater in the high TLR-4 group than the low TLR-4 group [9.61 (6.70-13.67) vs. 6.34 (4.27-9.09), P  < 0.01]. The expression of TLR-4 on CD14 ++ CD16 + monocytes was significantly correlated with CT-LeSc ( R2  = 0.13, P  < 0.01). The expression of TLR-4 on CD14 ++ CD16 + monocytes was significantly higher in patients who had future cardiac events than in those who did not [6.8 (4.5-9.1) % vs. 4.2 (2.4-7.6) %, P  = 0.04]. High TLR-4 expression on CD14 ++ CD16 + monocytes was an independent predictor for future cardiac events ( P  = 0.01)., Conclusion: An increase in the TLR-4 expression on CD14 ++ CD16 + monocytes is related to the development of future cardiac events., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The optimal ablation index (AI) value for cavotricuspid isthmus (CTI) ablation is unknow., Objective: This study investigated the optimal AI value and whether preassessment of local electrogram voltage of CTI could predict first-pass success of ablation., Methods: Voltage maps of CTI were created before ablation. In the preliminary group, the procedure was performed in 50 patients targeting an AI ≥450 on the anterior side (two-thirds segment of CTI) and AI ≥400 on the posterior side (one-third segment of CTI). The modified group also included 50 patients, but the target AI for the anterior side was modified to ≥500., Results: In the modified group, the first-pass rate of success was higher (88% vs 62%; P < .01) than in the preliminary group, and there were no differences in the average bipolar and unipolar voltages at the CTI line. Multivariate logistic regression analysis revealed that ablation with an AI ≥500 on the anterior side was the only independent predictor (odds ratio 4.17; 95% confidence interval 1.44-12.05; P < .01). The bipolar and unipolar voltages were higher at sites without conduction block than at sites with conduction block (both P < .01). The cutoff values for predicting conduction gap were ≥1.94 mV and ≥2.33 mV with areas under the curve of 0.655 and 0.679, respectively., Conclusions: CTI ablation with a target AI >500 on the anterior side was shown to be more effective than an AI >450, and local voltage at a conduction gap was higher than without a conduction gap., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

This study aims to compare the awareness-raising activities between municipalities with and without focused anti-infection measures during the 2019 coronavirus disease (COVID-19) pandemic. Descriptive analysis was conducted using a nationwide self-administered questionnaire survey on municipalities' activities for residents and for healthcare providers and care workers (HCPs) in October 2022 in Japan. This study included 433 municipalities that had conducted awareness-raising activities before 2019 Fiscal Year. Workshops for residents were conducted in 85.2% of the municipalities, and they were more likely to be conducted in areas with focused anti-infection measures than those without measures (86.8% vs. 75.4%). Additionally, 85.9% of the municipalities were impacted by the pandemic; 50.1% canceled workshops, while 26.0% switched to a web-based style. Activities for HCPs were conducted in 55.2-63.7% of the municipalities, and they were more likely to be conducted in areas with focused anti-infection measures. A total of 50.6-62.1% of the municipalities changed their workshops for HCPs to a web-based style. Comparisons between areas with and without focused anti-infection measures indicated that the percentages of those impacted for all activities were not significantly different. In conclusion, awareness-raising activities in municipalities were conducted with new methods during the COVID-19 pandemic. Using information technology is essential to further promote such activities for residents.

Sleep is regulated by peripheral tissues under fatigue. The molecular pathways in peripheral cells that trigger systemic sleep-related signals, however, are unclear. Here, a forward genetic screen in C. elegans identifies 3 genes that strongly affect sleep amount: sel-1, sel-11, and mars-1. sel-1 and sel-11 encode endoplasmic reticulum (ER)-associated degradation components, whereas mars-1 encodes methionyl-tRNA synthetase. We find that these machineries function in non-neuronal tissues and that the ER unfolded protein response components inositol-requiring enzyme 1 (IRE1)/XBP1 and protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor-2α (eIF2α)/activating transcription factor-4 (ATF4) participate in non-neuronal sleep regulation, partly by reducing global translation. Neuronal epidermal growth factor receptor (EGFR) signaling is also required. Mouse studies suggest that this mechanism is conserved in mammals. Considering that prolonged wakefulness increases ER proteostasis stress in peripheral tissues, our results suggest that peripheral ER proteostasis factors control sleep homeostasis. Moreover, based on our results, peripheral tissues likely cope with ER stress not only by the well-established cell-autonomous mechanisms but also by promoting the individual's sleep., Competing Interests: Declaration of interests The authors have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We sought to investigate the differences in coronary plaque morphology on coronary computed tomography angiography (CCTA) and medical therapy between acute coronary syndrome (ACS) and stable ischemic heart disease (SIHD). We also explored the relationship between plaque morphology on CCTA at the initial phase and lesion morphology in the acute phase of ACS., Methods: In 5967 patients who underwent invasive coronary angiography, 58 ACS and 91 SIHD patients who had prior CCTA imaging of the culprit lesion and denied ischemic heart disease at CCTA scanning were enrolled., Results: Although the prevalence of positive remodeling was not different (P = 0.27), low-attenuation plaques (LAP) on prior CCTA were significantly higher in ACS than in SIHD (52% vs. 24%, P < 0.01). The frequency of coronary stenosis grading did not differ between the two groups (P = 0.14). In ACS patients, the frequencies of plaque rupture and lipid-rich plaque assessed by optical coherence tomography (OCT) were significantly higher in LAP than in non-LAP (73% vs. 23%, P < 0.01; 82% and 23%, P < 0.01). Multivariate regression analysis revealed that statin use and LAP on prior CCTA were predictors of future ACS events (P < 0.01, and P < 0.05, respectively)., Conclusions: LAP on CCTA, not positive arterial remodeling, and lack of statin therapy were associated with ACS development. In addition, LAP more frequently led to the development of the plaque rupture type of ACS compared with non-LAP. Lipid-lowering therapy with statins might be useful to prevent plaque rupture in patients with LAP regardless of coronary stenosis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study investigates the prognosis of patients with postoperative atrial fibrillation (POAF), aiming to elucidate predictors of occurrence of atrial fibrillation (AF) in the chronic phase after esophagectomy., Methods: We retrospectively analyzed 415 consecutive patients between July 2010 and December 2021 who were scheduled to undergo esophagectomy for esophageal cancer and had no previous history of AF., Results: POAF occurred in 73 patients (18%). Their ages were higher than those without POAF (72 [66-77] vs 68 [62-75], P < 0.01). Three-field lymph node dissection was more frequent in patients with POAF (63% vs 50%, P = 0.04). Overall survival rates were not significantly different between those with and without POAF in patients with stage III/IV cancer (P = 0.37), but overall survival rate of patients with POAF was lower than in those without POAF in stage I/II cancer (P = 0.03). Seventeen patients (4.1%) had recurrence of AF or new onset 31 days after esophagectomy. POAF was the only independent predictor of AF development in the chronic phase (HR: 4.09, 95%CI: [1.42-11.74], P = 0.01). AF development in the chronic phase was observed in 8 patients (11.0%) with and 9 patients (2.6%) without POAF (P < 0.01). AF development rates were not significantly different in patients with stage III/IV cancer (P = 0.05), but there was significant difference in patients with stage I/II cancer (P < 0.01)., Conclusion: The occurrence of POAF after esophagectomy is related with future development of AF and overall survival prognosis. Future studies must ascertain optimal therapeutic strategy., (© 2022. The Society for Surgery of the Alimentary Tract.)

Decades of poor reproductive success and young-of-the-year survival, combined with adult mortality events, have led to a decline in the smallmouth bass (SMB; Micropterus dolomieu) population in sections of the Potomac River. Previous studies have identified numerous biologic and environmental stressors associated with negative effects on SMB health. To better understand the impact of these stressors, this study was conducted at the confluence of Antietam Creek and the Potomac River from 2013 to 2019 to identify temporal changes associated with SMB reproductive health. Surface water samples were collected and analyzed for over 300 organic contaminants, including pesticides, phytoestrogens, pharmaceuticals, hormones and total estrogenicity (E2Eq). Adult SMB were collected and sampled for multiple endpoints, including gene transcripts associated with reproduction (molecular), histopathology (cellular), and organosomatic indices (tissue). In males, biomarkers of estrogenic endocrine disruption, including testicular oocytes (TO) and plasma vitellogenin (Vtg) were assessed. Numerous agriculture-related contaminants or land use patterns were associated with gene transcript abundance in both male and female SMB. Positive associations between pesticides in the immediate catchment with TO severity and E2Eq with plasma Vtg in males were identified. In males, the prevalence of TO and detectable levels of plasma Vtg, liver vitellogenin transcripts (vtg) and testis vtg were high throughout the study. Peaks of complex mixtures of numerous contaminants occurred during the spring/early summer when spawning and early development occurs and to a lesser extent in fall/winter during recrudescence. Management practices to reduce exposure during these critical and sensitive periods may enhance reproductive health of these economically important sportfishes., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Skeletal alterations in the head and neck region, such as midfacial hypoplasia, foramen magnum stenosis and spinal canal stenosis, are commonly observed in patients with mucopolysaccharidosis (MPS). However, enzyme replacement therapy (ERT), one of the major treatment approaches for MPS, shows limited efficacy for skeletal conditions. In this study, we analysed the craniofacial morphology of mice with MPS type VII, and investigated the underlying mechanisms promoting jaw deformities in these animals. Furthermore, we investigated the effects of C-type natriuretic peptide (CNP), a potent endochondral ossification promoter, on growth impairment of the craniofacial region in MPS VII mice when administered alone or in combination with ERT. MPS VII mice exhibited midfacial hypoplasia caused by impaired endochondral ossification, and histological analysis revealed increased number of swelling cells in the resting zone of the spheno-occipital synchondrosis (SOS), an important growth centre for craniomaxillofacial skeletogenesis. We crossed MPS VII mice with transgenic mice in which CNP was expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP. The maxillofacial morphological abnormalities associated with MPS VII were ameliorated by CNP expression, and further prevented by a combination of CNP and ERT. Histological analysis showed that ERT decreased the swelling cell number, and CNP treatment increased the width of the proliferative and hypertrophic zones of the SOS. Furthermore, the foramen magnum and spinal stenoses observed in MPS VII mice were significantly alleviated by CNP and ERT combination. These results demonstrate the therapeutic potential of CNP, which can be used to enhance ERT outcome for MPS VII-associated head and neck abnormalities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kashiwagi 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.)

Incidents and accidents often involve the drinking of alcoholic beverages. We investigated compounds that indicate the consumption of alcoholic beverages even after ethanol (EtOH) becomes undetectable in blood and urine. Ethyl glucoside (EG) has been isolated as a possible drinking marker, and a GC-MS/MS method for EG isomers has been developed. EG isomers in several alcoholic beverages were analyzed. In sake, only αEG was observed in high concentrations. In wine and beer, both α and βEG were detected. Whisky, however, did not contain EG. EtOH and EG concentrations were analyzed in urine up to 48 h after ingestion. Maximum EtOH concentrations were reached in 1-2 h and was mostly eliminated in 6 h. Maximum EG concentrations were reached in 3-6 h, gradually decreased, and remained low after 24 h. After drinking sake, the αEG concentrations were much higher than that of other alcoholic beverages. After drinking wine or beer, βEG was detected, but lower than αEG. Also, αEG was detected in urine after drinking whisky that contained no EG. This suggested that αEG may be synthesized in vivo. Disaccharide-degrading enzymes such as α-glucosidase are present in the human small intestine. It was considered that αEG was synthesized when alcohol was consumed with certain foods, such as carbohydrates. In actual forensic autopsy cases, EtOH and EG isomer analysis provided useful information regarding drinking history. In conclusion, it is considered that urinary EG isomers can be used as drinking markers that complement EtOH analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

T cell differentiation requires Notch1 signaling. In the present study, we show that an enhancer upstream of Notch1 active in double-negative (DN) mouse thymocytes is responsible for raising Notch1 signaling intrathymically. This enhancer is required to expand multipotent progenitors intrathymically while delaying early differentiation until lineage restrictions have been established. Early thymic progenitors lacking the enhancer show accelerated differentiation through the DN stages and increased frequency of B, innate lymphoid (IL) and natural killer (NK) cell differentiation. Transcription regulators for T cell lineage restriction and commitment are expressed normally, but IL and NK cell gene expression persists after T cell lineage commitment and T cell receptor β VDJ recombination, Cd3 expression and β-selection have been impaired. This Notch1 enhancer is inactive in double-positive (DP) thymocytes. Its aberrant reactivation at this stage in Ikaros mutants is required for leukemogenesis. Thus, the DN-specific Notch1 enhancer harnesses the regulatory architecture of DN and DP thymocytes to achieve carefully orchestrated changes in Notch1 signaling required for early lineage restrictions and normal T cell differentiation., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

There is disparity between the sexes in cardiovascular diseases including heart failure (HF). This study aimed to investigate the effect of periodontal disease (PD) on plasma B-type natriuretic peptide (BNP) concentration across sex, age, and menopausal status, as well as the interaction effect of PD and diabetes mellitus (DM) on BNP. This large-scale prospective cohort study enrolled 7539 individuals with no myocardial infarctions or angina pectoris at baseline from the general Japanese population. The association between baseline number of missing teeth (MT) and the longitudinal changes in BNP over 5 years (ΔBNP) was evaluated according to sex and menopausal status. Among 7539 participants, 3190 were postmenopausal women with a mean age ± standard deviation of 61.1 ± 7.6 at baseline. Multivariate analysis revealed a positive association between MT and ΔBNP among postmenopausal women even after adjusting for covariates, including traditional HF risk factors (coefficient, 0.210; 95% confidence interval [CI], 0.107 to 0.312; P < 0.001), but not in men aged > 50. Including an interaction term (MT × DM) in the multivariate model revealed a positive interaction between MT and DM in ΔBNP among postmenopausal women (coefficient for interaction, 1.365; 95% CI, 0.902 to 1.827; P for interaction < 0.001). In conclusion, our study showed a positive association between MT and ΔBNP, as well as a positive effect of the interactive association between MT and DM, among postmenopausal women. Our results suggest a sex difference of an adverse effect of PD on initial myocardial wall stress in the ventricles., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was undertaken to determine the risk of bevacizumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analysed 5,273,115 reports and identified 20,399 reports of AEs caused by bevacizumab. Of these, 1679 lung toxicities were reportedly associated with bevacizumab. Signals were detected for nine lung toxicities. A histogram of times to onset showed occurrence from 35 to 238 days, but some cases occurred even more than one year after the start of administration. Approximately 20% of AEs were thromboembolic events. Among these, pulmonary embolism was the most frequently reported and fatal cases were also reported. The AEs showing the highest fatality rates were pulmonary haemorrhage, pulmonary infarction, and pulmonary thrombosis. In conclusion, we focused on lung toxicities caused by bevacizumab as post-marketing AEs. Some cases could potentially result in serious outcomes, patients should be monitored for signs of onset of AEs not only at the start of administration, but also over a longer period of time., (© 2022. The Author(s).)

Carbapenem-resistant bacteria represent an emerging threat to global health; nursing homes may be reservoirs for these isolates, which cause life-threatening infections. Here, we present the complete genome sequence of an Enterobacter roggenkampii strain with reduced carbapenem susceptibility that was isolated from a sink in a home-visit nursing agency.

Background: Patients with acute myocardial infarction (AMI) caused by calcified nodules (CN) have worse clinical outcomes following primary percutaneous coronary intervention (PCI). This study investigated the late vascular response after everolimus-eluting stent (EES) implantation assessed by optical coherence tomography (OCT) in patients with AMI caused by CN, by comparing with plaque rupture (PR) and plaque erosion (PE)., Methods and results: Based on the OCT findings in AMI culprit lesions before PCI, a total of 141 patients were categorized into 3 groups (PR, PE, or CN), and the OCT findings immediately and 10 months after PCI were compared. The frequency of PR, PE, and CN was 85 (60%), 45 (32%), and 11 patients (8%), respectively. In the 10-month follow-up OCT, the frequency of lesions with uncovered struts and lesions with malapposed struts were highest in the CN group, followed by the PR and PE groups (82% vs. 52% vs. 40%, P=0.042 and 73% vs. 26% vs. 16%, P<0.001, respectively). The incidence of intra-stent thrombus, re-appearance of CN within the stent, and target lesion revascularization were higher in the CN group compared with the PR and PE groups (36% vs. 9% vs. 7%, P=0.028; 27% vs. 0% vs. 0%, P<0.001; and 18% vs. 2% vs. 2%, P=0.024, respectively)., Conclusions: Late arterial healing response at 10 months after EES implantation in the CN was worse compared with PR and PE in patients with AMI.

Aim: This study aimed to determine the incidence of occupational accidents among home-visiting nurses from home-visit nursing agencies and relevant factors., Methods: Data from a questionnaire survey, conducted in March 2020, concerning home-visit nursing agencies were used as a secondary source. A total of 9979 agencies were surveyed. The questionnaires included items relating to the number of occupational accidents experienced by visiting nurses that occurred during a 3-month period. The occurrence of accidents in an agency was set as a dependent variable, and logistic regression analysis was performed on its association with agency attributes. For agencies in which accidents occurred, the number of accidents per 10 full-time-equivalent nurses was estimated, and multiple regression analysis was administered to investigate its association with agency attributes., Results: The findings of the logistic regression analysis revealed that new agencies, a greater number of full-time-equivalent nurses, emergency visitation support, and performing an analysis of accident cases for accident prevention were significantly associated with the occurrence of accidents. A median of 3.3 accidents occurred per 10 full-time-equivalent nurses at such agencies. Multiple regression analysis showed that a lower number of full-time-equivalent nurses was significantly associated with an increase in the frequency of accidents., Conclusions: These results suggest that to devise and deploy safety measures for visiting nurses, all home-visit nursing agencies must build reporting and analysis systems for occupational accidents among home-visiting nurses. Moreover, ensuring safety measures for nurses working in small-scale agencies is of utmost importance. Geriatr Gerontol Int 2022; 22: 588-596., (© 2022 Japan Geriatrics Society.)