Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

Development of molecular sensors based on fluorescent proteins for polarized macrophages identification.

Macrophages are a type of white blood cells that play key roles in innate immune responses as a part of cellular immunity for host defence and tissue homeostasis. To perform diverse functions, macrophages show high plasticity by transforming to polarized states. They are mainly identified as unpolarized, pro-inflammatory and antiinflammatory states and termed as M0, M1 and M2 macrophages respectively. Discriminating polarized states is important due to strict implication with inflammatory conditions resulting in many diseases as chronic inflammation, neurodegeneration, and cancer etc. Many polarization protein markers have been identified and applied to investigate expression profiles through PCR and other techniques with antibodies. However, they are time and cost consuming and sometimes show insufficient performances. We focused on the mannose receptor (CD206) as representative marker of M2 macrophage recognising terminal mannose. We developed dose dependent mannosylated fluorescent proteins (FPs) by conjugations with mannose derivative for around 20 modifiable sites on FPs surfaces. Maximum modifications did not spoil various features of FPs. We found further sensitive and specific discriminations among M2, M1 and M0 macrophages after treating polarized macrophages with adequately conditioned FPs compared to already established approaches using anti CD206 antibody through flow cytometric analysis. These results might be derived from direct ligand utilizations and increased avidity due to multivalent bindings with abundantly modified multimeric FPs. Our strategy is simple but addresses disadvantages of preceding methods. Moreover, this strategy is applicable to detect other cell surface receptors as FPs can be modified with ligands or recognizable aptamer like molecules.

Self-Assembly of Silole-Based Aggregation-Induced Emission Compounds with Green Fluorescent Protein under Physiological Conditions for Traceable and Versatile Drug Delivery.

Biomacromolecules are viewed as promising drugs due to their specific functions in biological processes, biocompatibility, and pharmacological efficacy. Injective administration, chosen to avoid intestinal barriers, may in turn lead to immediate decay in the circulation system, unreliable targeting performance, or the induction of immune responses. For some biomacromolecules, chemically modified proteins have been developed for practical use. Various cargo or carrier systems are under development but have been delayed by technical difficulties. We present self-assembled nanocapsules with diameters ranging from 100 to 500 nm that can be deployed in physiological buffers to enclose various substances present in the buffers at the same time. Our amphiphilic nanocapsule, consisting of silole-core dendrimer products as the hydrophobic part and green fluorescent protein (GFP) derivatives as the hydrophilic part, connects and assembles spontaneously when mixed in solutions while engulfing dissolved or dispersed compounds together in a dose-dependent manner and shows unique optical characteristics because the dendrimer products exhibit aggregation-induced emission. Furthermore, the emission of the dendrimer causes considerable fluorescence resonance energy transfer (FRET) to GFP derivatives upon association. We could easily monitor assemblies by FRET states and particle sizes and have confirmed a stable presence in the buffer for at least a month. Further tracking of nanocapsules by fluorescence confirmed efficient uptake into some cancer cells. Nanocapsules based on GFP variants with or without a cell-surface-specific tag demonstrated that the tag improved the potential for specific targeted delivery. There were also indications that the nanocapsules became unstable after cellular uptake in the intracellular environment. We report here the simple preparation of traceable, stable, and biocompatible self-assembled nanocapsules as the basis for a versatile drug delivery system.

Study on Fast Liquefaction and Characterization of Produced Polyurethane Foam Materials from Moso Bamboo.

Although bamboo is widely distributed in Japan, its applications are very limited due to its poor combustion efficiency for fuel. In recent years, the expansion of abandoned bamboo forests has become a social issue. In this research, the possibility of a liquefaction process with fast and efficient liquefaction conditions using moso bamboo as raw material was examined. Adding 20 wt% ethylene carbonates to the conventional polyethylene glycol/glycerol mixed solvent system, the liquefaction time was successfully shortened from 120 to 60 min. At the same time, the amount of sulfuric acid used as a catalyst was reduced from 3 wt% to 2 wt%. Furthermore, polyurethane foam was prepared from the liquefied product under these conditions, and its physical properties were evaluated. In addition, the filler effects of rice husk biochar and moso bamboo fine meals for the polyurethane foams were characterized by using scanning electron microscopy (SEM) and thermogravimetry and differential thermal analysis (TG-DTA), and the water absorption and physical density were measured. As a result, the water absorption rate of bamboo fine meal-added foam and the thermal stability of rice husk biochar-added foam were improved. These results suggested that moso bamboo meals were made more hydrophilic, and the carbon content of rice husk biochar was increased.

Comparing health care outcomes before and after employing nurse practitioners in cardiovascular hospitals in Japan: A retrospective chart review.

BACKGROUND: There are approximately 872 certified nurse practitioners (NPs) in Japan as of April 2024. However, research on the results of their specific activities is still scarce. PURPOSE: This study aimed to compare health care outcomes before (i.e., 2019) and after (i.e., 2021) employing NPs in cardiovascular hospitals in Japan. METHODOLOGY: We conducted a retrospective chart review and analyzed 114 patients who underwent cardiac surgery in Hospital A and 381 patients who received pacemaker implantation/replacement in Hospital B. Hospital A hired one NP for cardiac surgery service, and Hospital B hired one NP for pacemaker device service. The NPs assisted in the surgical procedures and provided postsurgical management. RESULTS: In Hospital A, the median length of hospitalization and intubation were shorter in 2021 than in 2019 (p = .02 and .01, respectively). In Hospital B, medical fee reimbursement was lower in 2021 (p < .001) than in 2019, and the median procedure duration was shorter (p = .01), which remained statistically significant after controlling for age, comorbidities, and device types. Some outcomes improved following the employment of NPs, whereas others remained unchanged. CONCLUSIONS: Nurse practitioners managed surgical patients well and contributed to the quality care of cardiovascular medicine. IMPLICATIONS: The employment of NPs in Japan is encouraged because even a single NP can have a positive, although not large, impact on patients and organizations.

Culinary continuity in central Japan across the transition to agriculture.

Rice and millet arrived in Western Japan from Korea around 3,000 years ago and spread eastwards across the archipelago in the next 700 years. However, the extent to which agriculture transformed traditional Jomon hunter-gatherer-fisher communities is debated. Central Japan is a key area of study as remodelling of radiocarbon dates shows a slowdown in the dispersal rate of rice agriculture in this area. Here, we examine and compare the use of pottery by Final Jomon and Early to Middle Yayoi communities in the Tokai and the Central Highland regions of central Japan, using lipid residue analysis. Although the identification of specific biomarkers for rice remains elusive, an increase in the ratio of E/H C18 APAAs with the arrival of rice and millet indicates a potential change in plant processing and consumption. We were also able to identify biomarkers for broomcorn millet (miliacin) in both Final Jomon and Yayoi pottery. However, evidence for millet consumption is sparse and in all cases was likely mixed with wild hunted and foraged foods. We conclude therefore that, despite the introduction of rice and millet agriculture in central Japan, pre-existing diets and culinary habits of Jomon hunter-gatherers remain important. Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-024-01992-9.

Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues.

Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

Live Cell Monitoring of Separase Activity, a Key Enzymatic Reaction for Chromosome Segregation, with Chimeric FRET-Based Molecular Sensor upon Cell Cycle Progression.

Separase is a key cysteine protease in the separation of sister chromatids through the digestion of the cohesin ring that inhibits chromosome segregation as a trigger of the metaphase-anaphase transition in eukaryotes. Its activity is highly regulated by binding with securin and cyclinB-CDK1 complex. These bindings prevent the proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties in biochemical examinations due to the instability of separase in vitro and the fact that few spatiotemporal resolution approaches exist for monitoring live separase activity throughout mitotic processes. Here, we have developed FRET-based molecular sensors, including GFP variants, with separase-cleavable sequences as donors and covalently attached fluorescent dyes as acceptor molecules. These are applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated the performance of equivalent molecular sensors, either localized or not localized inside the nucleus under cell cycle control, using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems that can be used specifically or statistically, which could lead to the elucidation of separase properties in detail.

Prevalence, Risk Factors, and Perinatal Outcomes of Velamentous Umbilical Cord Insertion in Twin Pregnancies: A Single-Center Retrospective Study.

BACKGROUND: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. METHODS: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. RESULTS: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at <36 weeks. CONCLUSIONS: VCI was a prominent risk factor for adverse perinatal outcomes only in MCDA twins. Antenatal sonographic assessment of the umbilical cord insertion site would be beneficial.

Applicability of Nursing Support for Patients With Terminal Cancer and Their Families: A Delphi Study.

BACKGROUND: This report investigates the applicability of nursing support for patients with cancer with a prognosis of months and weeks, and their families. OBJECTIVES: To evaluate the applicability of nursing support for five symptoms (dyspnea, pain, nausea/vomiting, constipation, and delirium) in patients with cancer during the last weeks of life, and the caregiver burden on their families. DESIGN SETTING: A Delphi study was used to determine the applicability of nursing support for patients with terminal cancer and their families. Eight experts in symptom palliation in Japan who have direct care or research experience with these populations were included. The Delphi method was used to assess nursing support types for prognoses of months and weeks. Consensus was defined as ≥70% agreement for either "high applicability" or "low applicability" of each support type. RESULTS: A total of 50 nursing support types for 5 symptoms were evaluated as highly applicable for 92% (n = 46) of patients with cancer with a prognosis of months. For patients with cancer with a prognosis of weeks, 78% (n = 39) of the nursing support was rated as highly applicable. For both prognosis groups, all nursing support (n = 6) for caregiver burden was highly applicable. CONCLUSION: Applicability ratings of nursing support may be influenced by a high degree of invasiveness, accessibility of knowledge and information, and high expectations of effectiveness. Future studies are needed to verify the effectiveness of nursing support evaluated as highly applicable to patients with cancer during the last few months and weeks of life.

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

Insomnia symptoms and related factors in a community-based population: The Yamagata Cohort study.

Objective/background: Insomnia is prevalent and is a risk factor for the development of lifestyle-related diseases and early death. To improve insomnia, it is necessary to identify the factors that affect it. This study investigated the associations between insomnia symptoms and mental, physical, and environmental factors in the general Japanese population. Patients/methods: The study participants were 7,873 individuals who responded to the Health and Lifestyle Survey questionnaire that included sleep-related items between December 2021 and March 2022. Insomnia symptoms were defined as a score of 6 or higher on the Athens Insomnia Scale (AIS). A multivariate logistic regression analysis was performed to identify factors independently associated with insomnia symptoms. Results: Of all subjects, 23.4% had insomnia symptoms. Factors associated with insomnia symptoms were older age, female sex, very difficult living conditions on current income, pain/discomfort, anxiety, lack of happiness, frequent nocturia, long duration from bathing time to bedtime, bedroom lighting, and short walking duration. The subgroup analysis showed stronger associations between walking time in men, higher body mass index in women, time from bathing time to bedtime, and daily walking duration in older adults. Conclusions: Insomnia symptoms were common in community-based populations and were independently associated with three different factor groups including physical, psychological, and environmental factors. Improvements in insomnia symptoms require appropriate practical support tailored to an individual's situation.

Relationship between food group-specific intake and depression among local government employees in Japan.

BACKGROUND: We aimed to examine the relationship between food group-specific intake and depression among workers in Japan. METHODS: A questionnaire survey was administered to 568 workers in 2020; 503 workers responded and 423 were included in the study. Information on sex, age, body mass index, overtime hours, sleep duration, marital status, employment position, exercise habits, smoking status, incidence of depression, and intake of energy, proteins, lipids, carbohydrates, alcohol, and specific food groups were collected. The Center for Epidemiologic Studies Depression Scale was used to assess the presence and severity of depression. Food group-specific intake was adjusted for energy intake using the residual method and classified into low, moderate, and high by sex. Logistic regression was used to examine the odds ratios (ORs) and trends according to sex, with the presence/absence of depression as the dependent variable and food group-specific intake as the independent variable. RESULTS: Men in the eggs low-intake, and women in the other vegetables low- and moderate-intake and eggs moderate-intake groups had significantly higher adjusted ORs (aORs) for depression. Additionally, a dose-response relationship was observed, where the OR for depression was significantly higher in men when the intake of eggs was low (p for trend = 0.024) and in women when the intakes of other vegetables (p for trend = 0.011) and eggs (p for trend = 0.032) were low. CONCLUSIONS: The intake of eggs in men and eggs and vegetables in women may be related to depression.

Endometrial Cancer with and without Endometriosis: Clinicopathological Differences.

Endometriosis is known to be associated with an increased risk of endometrioid and clear cell ovarian cancer. However, the association between endometriosis and endometrial cancer is controversial. Therefore, we retrospectively analyzed the medical records of women with endometrial cancer who had undergone surgery at our institution to evaluate the clinicopathological relationship between endometrial cancer and endometriosis. The study included 720 women pathologically diagnosed with endometrial cancer at our hospital between 2000 and 2020. The participants were allocated to two groups of patients with endometrial cancer: patients with endometriosis (n = 101) and patients without endometriosis (n = 619). Endometrial cancer patients with endometriosis were significantly younger (median age 54.0 vs. 58.0; p = 0.002). In addition, endometrial cancer patients with endometriosis had fewer pregnancies and deliveries (median pregnancy 1.58 vs. 1.99; p = 0.019, median delivery 1.25 vs. 1.56; p = 0.012). The percentage of patients classified as stage IA was significantly higher in those with endometrial cancer with endometriosis (68.3% vs. 56.4%; p = 0.029). In the analysis of synchronous ovarian cancer, the percentage of dual primary cancer was higher in patients with endometriosis (14.9% vs. 1.6%; p < 0.001). The association of young-onset early-stage endometrial cancer with endometriosis is an important finding that cannot be ignored clinically.

Lessons from the "Humanization of Childbirth" Projects: Qualitative analysis of seven projects funded by the Japan International Cooperation Agency.

The "Humanization of Childbirth" Project is one of the various maternity care models that respect women and their newborn children. For more than a quarter of a century, the Japan International Cooperation Agency (JICA) has been implementing technical cooperation projects worldwide that place the humanization of childbirth at the center of the concept. By reviewing the project reports, the following 11 key processes were found for the formulation and implementation of future projects for the humanized maternity care: i) project-finding/exploration of unmet needs, ii) identification of local key persons, iii) organization of a project team and a back-up committee, iv) development of an action plan, v) sharing of concepts, vi) development of local leadership, vii) organization of infrastructure, viii) final evaluation and wrap-up seminar, ix) ensuring sustainability, x) development of younger generation experts, and xi) sustainable and autonomous action.

Nursing support for breathlessness in patients with cancer: a scoping review.

OBJECTIVE: To identify nursing support provided for the relief of breathlessness in patients with cancer. DESIGN: A scoping review following a standard framework proposed by Arksey and O'Malley. STUDY SELECTION: Electronic databases (PubMed, CINAHL, CENTRAL and Ichushi-Web of the Japan Medical Abstract Society Databases) were searched from inception to 31 January 2022. Studies reporting on patients with cancer (aged ≥18 years), intervention for relief from breathlessness, nursing support and quantitatively assessed breathlessness using a scale were included. RESULTS: Overall, 2629 articles were screened, and 27 were finally included. Results of the qualitative thematic analysis were categorised into 12 nursing support components: fan therapy, nurse-led intervention, multidisciplinary intervention, psychoeducational programme, breathing technique, walking therapy, inspiratory muscle training, respiratory rehabilitation, yoga, acupuncture, guided imagery and abdominal massage. CONCLUSIONS: We identified 12 components of nursing support for breathlessness in patients with cancer. The study results may be useful to understand the actual state of nursing support provided for breathlessness in patients with terminal cancer and to consider possible support that can be implemented.

Preparation of a Water-Soluble Glycopolymer Bearing Porphyrin Skeletons and Its Biological Properties.

A known tetraphenyl porphyrin (TPP) having an amino functional group [5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin] was converted into the corresponding monomer by means of condensation with acryloyl chloride. Simple radical polymerization of the porphyrin monomer and a glycosyl monomer in the presence of acrylamide as a regulator monomer in order to avoid steric interference gave a water-soluble glycopolymer bearing porphyrin moieties. Spectroscopic analyses suggested incorporation of porphyrin moieties in the glycopolymer. The physical properties of the water-soluble glycopolymer bearing porphyrin moieties were examined in aqueous media, and the results also indicated the incorporation of TPP moieties in the polymer. Uptake of the polymer into HeLa cells was observed, and the cytotoxicity of the polymer was confirmed by microscopic analyses. The glycopolymer bearing porphyrin moieties is promising not only for photodynamic therapy but also as an anti-cancer reagent.

TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.

Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.

Building Relationships Between Community Care Professionals and Convenience Stores in Japan: Community-Based Participatory Research.

BACKGROUND: Convenience stores play an important role in supporting community-dwelling older adults' lives. We started community-based participatory research (CBPR) in Nerima City, Tokyo Metropolitan area in Japan to develop a collaborative relationship to support older adults in the community-based integrated care system. OBJECTIVES: This study aimed to describe the CBPR process and evaluate building face-to-face relationships between health/social care professionals and the owners/employees of convenience stores. METHODS: Using CBPR, health/social care professionals in community general support centers (CGSCs) directly approached convenience stores based on the public support agreement between the convenience store chain company and the municipality. To evaluate the face-to-face relationship building between convenience store owners/employees and CGSCs' staff, we administered questionnaire surveys to convenience stores in Nerima City and two control cities from 2017 to 2019, and about 100 convenience stores completed the survey each year. RESULTS: Statistical analyses showed significant improvements in their knowledge for relationships with the CGSCs in Nerima City, including "knowledge of the CGSCs' function" (P = 0.001), "knowing individual professionals in the CGSCs" (P = 0.023), and "knowledge of when to contact the CGSCs" (P = 0.002), compared with control cities. Helping behavior for older adults at convenience stores also increased significantly in Nerima City (P = 0.034). CONCLUSIONS: The CGSCs' direct approach based on the public support agreement would effectively promote building relationships at convenience stores, leading to an age-friendly community.