Search

Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25–50 μM, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)-mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation.

Summary: The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual’s immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells. We find that hydrophobic complementarity-determining region (CDR)3 residues promote regulatory T cell fates in both the CD8 and CD4 lineages. Most strikingly, we find a set of TCR sequence features that promote the T cell transition from naive to memory. We quantify the extent of these features through our TCR scoring function “TCR-mem.” Using TCR transduction experiments, we demonstrate that increased TCR-mem promotes T cell activation, even among T cells that recognize the same antigen. Our results reveal a common set of TCR sequence features that enable T cell activation and immunological memory.

We discovered that the phospholipids present in the internal organs of scallops (Patinopecten yessoensis), which are primarily composed of glycerophospholipids and ceramide 2-aminoethylphosphonate (CAEP), reduced the serum and liver cholesterol contents in mice. This study evaluated the effects of scallop CAEP on lipid metabolism by comparing it to sphingomyelin. The study involved feeding four-week-old male KK-Ay mice either a high-fat diet or a high-fat diet supplemented with 0.5 wt% each of CAEP and sphingomyelin for 35 days. We found that CAEP intake lowered the serum triacylglycerol content, partly via a reduction in the mRNA expression levels of fatty acid synthesis-related genes in the liver. Furthermore, the CAEP diet reduced the serum and liver cholesterol contents. This effect was partially mediated by the increase in fecal total sterol excretion. Thus, this study indicates CAEP will be employed as a health-promoting component to lower the body’s triacylglycerol and cholesterol contents.

Background: The relationship between patterns of outpatient oral loop diuretic (LD) dose reduction and prognosis in patients with heart failure (HF) remains unclear. Methods: We evaluated 679 patients with HF-prescribed LDs at baseline between September 2015 and August 2019. Dose reduction was defined as a change to a lower LD dose than the previous outpatient dose. Dose intensification was defined as a change to a higher LD dose than the previous outpatient dose. Patients were classified into no-reduction (no LD dose reduction during follow-up) and reduction groups (categorized into successive-reduction [≥2 successive LD dose reductions without intervening LD dose intensification] and single-reduction [LD dose reduction without successive dose reduction] groups). The primary outcomes were all-cause death, HF hospitalization (HFH), and the composite of cardiovascular death (CVD) or HFH. Results: Within a median follow-up of 53.7 (range, 2.6–99.1) months, 156 deaths were recorded: 121 (29 %), 31 (15 %), and three (4 %) patients in the no-reduction (n = 411), single-reduction (n = 195), and successive-reduction (n = 73) groups, respectively. After adjusting for cofounders, the reduction group had a lower risk of primary outcomes than the no reduction group (all-cause death: hazard ratio (HR) = 0.65, 95 % confidence interval (CI) = 0.44–0.96; CVD or HFH: HR=0.69, 95 %CI=0.52–0.93; HFH: HR=0.69, 95 % CI=0.52–0.93). The successive-reduction group had a lower risk of the composite of CVD or HFH (HR=0.26, 95 % CI: 0.10–0.67) and HFH (HR=0.34, 95 % CI=0.13–0.86) than the single-reduction group. Conclusions: Outpatient LD dose reduction patterns can be indicators of good prognosis in HF patients.

Circadian disruption is an important factor driving the current-day high prevalence of obesity and type-2 diabetes. While the impact of incorrect timing of caloric intake on circadian disruption is widely acknowlegded, the contribution of incorrect timing of physical activity remains relatively understudied. Here, we modeled the incorrect timing of physical activity in nightshift workers in male Wistar rats, by restricting running wheel access to the innate inactive (light) phase (LR). Controls included no wheel access (NR); access only during the innate active (dark) period (DR); or unrestricted (ad libitum) access (ALR). LR did not shift the phase of the muscle or liver clock, but dampened the muscle clock amplitude. As our previous study demonstrated that light-phase restricted feeding did shift the liver clock, but made the muscle clock arrhythmic, we next combined the time restriction of wheel and food access to either the light phase (LRLF) or dark phase (DRDF). LRLF produced a ∼12 h shift in the majority of clock gene rhythms in both skeletal muscle and liver. On the other hand, DRDF was most effective in reducing body weight and the accumulation of fat mass. Therefore, in order to shift the muscle clock in male Wistar rats, synergy between the timing of feeding and physical activity is necessary. These findings may contribute to further improve the design of lifestyle strategies that try to limit metabolic misalignment caused by circadian disruption.

Introduction: To elucidate factors associated with severe disease in patients with coronavirus disease 2019 (COVID-19) pneumonia complicated with diabetes mellitus. Methods: Among patients with COVID-19 pneumonia hospitalized from January to September 2021, 100 patients with diabetes were included in the study. Patients in the intensive care unit admission or in-hospital death category were defined as the severe group (26 patients), and the other patients as the moderate group (74 patients). Comparisons were made between the two groups. Medical histories were extracted from the medical records, and statistical analysis was performed. Results: Patients were 62.1 ± 13.0 years of age, 70 % male, 48 % aged 65 years and more, and HbA1c was 7.72 ± 1.51 %. The severe group had significantly higher blood glucose level, CRP, WBC, and LDH on admission. Serum albumin level was significantly lower in the severe group and was significantly negatively correlated with number of days on oxygen administration (r = 0.447) and maximal oxygen concentration (r = 0.561). Multiple logistic regression analysis with severity of illness as the objective variable showed that high CRP and low albumin levels on admission, and older age were independently associated. Conclusions: Low albumin levels on admission may be an indicator of severe disease in patients with diabetes.

Summary: Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical outcomes in patients with relapsed/refractory B cell leukemias; however, response rates in patients with large B cell lymphoma (LBCL) are less impressive. Expression of PD-1 on activated T cells and PD-L1 on malignant, stromal, and immune cells within the tumor microenvironment (TME) contribute to CAR-T exhaustion, hypofunction, and treatment failures. Here, a comparative approach is taken to develop a chimeric switch receptor (CSR) with potential to augment CAR-T persistence, function, and clinical efficacy in immune competent, pet dogs with spontaneous B cell lymphoma (BCL). We show that similar to human CAR-T cells, expression of a PD-1/CD28 CSR in canine CAR-T cells results in enhanced function against PD-L1+ targets and preserves central memory phenotype. We also demonstrate that these effects depend upon active CSR signaling. This work paves the way for in vivo studies in canine BCL patients to inform human trial design.

Objective: To investigate the feasibility of poststroke interventions using a motivational instructional design model with occupational therapy (OT) and swallowing therapy (ST) and the model's potential physical and mental health effects. Design: An open-label, single-arm, feasibility study on the Attention, Relevance, Confidence, and Satisfaction model. Setting: Two convalescent rehabilitation wards. Participants: Twenty-five patients with stroke (N=25) (19 men; mean age, 62.4±11.9y; 61.9±36.8d from the first stroke) were recruited. Interventions: Twelve participants received a motivational approach based on the Attention, Relevance, Confidence, and Satisfaction model during OT (OT group), and 13 received it during ST (ST group). The intervention lasted 40-60 minutes daily, 5 days weekly, for 4 weeks. Main Outcome Measures: The primary outcomes included the dropout rate, an adverse event, and the participants’ acceptability of the intervention. Paretic arm function was assessed in the OT group; swallowing ability was assessed in the ST group; and activities of daily living, depressive symptoms, and apathy were assessed in both groups. Results: No participants dropped out of the intervention or experienced an adverse event. Twenty-one participants (84%) were satisfied with the intervention, and 19 (76%) hoped to continue receiving it. The OT group showed statistically significant improvements in paretic arm function and activities of daily living (Cohen's r=0.68-0.77), whereas the ST group improved in swallowing ability, activities of daily living, and depressive symptoms (Cohen's r=0.62-0.85). Conclusions: The interventions using the motivational instructional model with OT and ST were feasible and could improve poststroke paretic arm function, swallowing ability, and activities of daily living after stroke.

Background: In clinical research on multifactorial diseases such as atopic dermatitis, data-driven medical research has become more widely used as means to clarify diverse pathological conditions and to realize precision medicine. However, modern clinical data, characterized as large-scale, multimodal, and multi-center, causes difficulties in data integration and management, which limits productivity in clinical data science. Methods: We designed a generic data management flow to collect, cleanse, and integrate data to handle different types of data generated at multiple institutions by 10 types of clinical studies. We developed MeDIA (Medical Data Integration Assistant), a software to browse the data in an integrated manner and extract subsets for analysis. Results: MeDIA integrates and visualizes data and information on research participants obtained from multiple studies. It then provides a sophisticated interface that supports data management and helps data scientists retrieve the data sets they need. Furthermore, the system promotes the use of unified terms such as identifiers or sampling dates to reduce the cost of pre-processing by data analysts. We also propose best practices in clinical data management flow, which we learned from the development and implementation of MeDIA. Conclusions: The MeDIA system solves the problem of multimodal clinical data integration, from complex text data such as medical records to big data such as omics data from a large number of patients. The system and the proposed best practices can be applied not only to allergic diseases but also to other diseases to promote data-driven medical research.

Purpose: This prospective multicenter study investigated the implant fixation of a cementless cup in primary total hip arthroplasty (THA) for osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH) in Japanese patients. Methods: Ten hospitals in Japan were enrolled in this study. The cohort comprised 267 hips in 228 Japanese patients who underwent primary THA for OA secondary to DDH. An acetabular cup with advanced in-growth, GRIPTION™ coating, was used in all patients. Mean age at surgery was 66.9 (range 45–89) years, and 201 patients (239 hips) were female. Of these patients, 89.1 ​% (238/267) was Crowe group I. Radiolucent lines around the cup, osteolysis, cup migration, grafted bone status, and clinical scores were evaluated preoperatively and at 6 months, 1 year, and 2 years postoperatively. Adverse events were evaluated throughout the study. Implant survivorship was assessed using the Kaplan–Meier method. Results: Nine hips had radiolucent lines ≥2 ​mm that resolved by 6 months. All cups showed bone in-growth and no cups loosened. At 2 years, the bone grafts had remodeled and incorporated in 68 ​% (43/63) of hips. There were four systemic and five surgical site events, and one procedure-related dislocation. The survivorship with cup revision as the endpoint was 99.6 ​% (95 ​% confidence interval, 97.3–99.9). All clinical scores were improved at 2 years compared with preoperatively (p ​

Background: Although the prevalence rate of valvular heart disease (VHD) is high in patients with systemic lupus erythematosus (SLE), the predictive factors of concomitant VHD have not been fully evaluated. Methods and results: Among 288 patients with SLE who underwent transthoracic echocardiography at Kumamoto University Hospital from 2016 to 2021, 241 patients with sufficient echocardiographic data were retrospectively analysed. Among them, 22 (9 %) had VHD (10 had mitral regurgitation, 3 had aortic regurgitation, 6 had tricuspid regurgitation, 1 had mitral regurgitation and tricuspid regurgitation, and 2 had a prosthetic cardiac valve). After excluding the two patients with a prosthetic cardiac valve, we divided the remaining patients into two groups: the VHD group and non-VHD group. Multivariate logistic regression analysis revealed that age and the platelet count were significantly and independently associated with having VHD (age: odds ratio, 1.06; 95 % confidence interval, 1.02–1.10; p

Nalmefene, an antagonist of mu- and delta-opioid receptors and a partial agonist of kappa-opioid receptors, has shown promise in reducing alcohol consumption among patients with alcohol dependence. Opioid receptors play pivotal roles in various physiological processes, including those related to peripheral inflammatory diseases such as colitis and arthritis, as well as functions in the immune system and phagocytosis. Atherosclerosis, a chronic inflammatory disease, progresses through the phagocytosis and uptake of oxidized low-density lipoprotein (oxLDL) by macrophages in atherosclerotic plaques. Despite this knowledge, it remains unclear whether nalmefene influences the formation of atherosclerotic plaques and increases the risk of serious cardiovascular events. This study aims to elucidate the impact of nalmefene on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and peritoneal macrophages in vitro.In this experiment, 8-week-old male ApoE KO mice were fed a high-fat diet intraperitoneally administered either vehicle (saline) or nalmefene (1 mg and 3 mg kg−1 day−1) for 21 days. Oil red O-staining and immunohistochemistry with an anti-MOMA2 (monocyte/macrophage) antibody showed that a dose-dependent increase in atherosclerotic plaque formation and augmentation of macrophage-rich plaque formation in ApoE-KO mice. Further investigations focused on the effects of nalmefene on the expression of scavenger receptor CD36 in RAW264.7 cells, conducted through western blotting analysis. Nalmefene demonstrated a significant increase in CD36 protein expression in RAW264.7 cells. To explore the impact on oxidized LDL uptake in peritoneal macrophages, cells were treated with nalmefene (300 μg/mL) for 24 h, followed by the addition of DiI-labeled oxLDL (DiI-oxLDL) for 4 h. Nalmefene significantly enhanced DiI-oxLDL uptake in macrophages. Additionally, treatment with nalmefene (300 μg/mL) for 24 h decreased the mRNA expression of mu-, delta-, and kappa-opioid receptors in RAW264.7 cells.In conclusion, nalmefene may augment oxLDL uptake by macrophages through increased CD36 expression and decreased opioid receptor, thereby contributing to atherosclerotic plaque formation and vulnerability. Consequently, the use of nalmefene may be associated with an elevated risk of cardiovascular events.

The transverse vaginal septum, a rare Müllerian duct anomaly, presents diagnostic and therapeutic challenges owing to its variable location, thickness, and potential association with uterine malformations. Therefore, an accurate diagnosis and selection of an appropriate treatment are important. Herein, the case of a 28-year-old nonpregnant woman with sexual dysfunction attributable to a transverse vaginal septum is presented. The septum, approximately 5 mm thick, was situated low on the vaginal wall near the urethral opening, with a small central aperture. Employing YV plasty, full extension of the posterior and lateral vaginal walls was achieved while minimizing the manipulation of the anterior wall to avoid urethral injury. Postoperatively, the patient achieved sexual function without vaginal stenosis. YV plasty is a minimally invasive and effective approach for preventing postoperative stenosis in the treatment of a thin transverse vaginal septum located low on the vaginal wall.

Introduction: Osteoarthritis (OA) is the most common form of arthritis. OA results from the breakdown of cartilage, which leads to deterioration of the entire joint and the connective tissue that holds the joint together, and gradually and irreversibly worsens over time. Adipose-derived stem/stromal cells (ADSCs) have been used in the treatment of knee OA. However, the safety and efficacy of ADSC treatment of OA remain unclear. In this study, we investigated the pathophysiology of severe knee arthritis that occurred after ADSC treatment by screening for autoantibodies in synovial fluid from patients who received ADSC treatment. Methods: Adult Japanese patients with OA who received ADSC treatment at Saitama Cooperative Hospital between June 2018 and October 2021 were enrolled. Antibodies (Abs) were screened using immunoprecipitation (IPP) with [35S]-methionine-labeled HeLa cell extracts. The detected protein was identified by liquid chromatography coupled with time-of-flight mass spectrometry (MS) and ion trap MS, and the corresponding proteins were confirmed as autoantigens using immunoblotting. Ab titers were measured using an enzyme-linked immunosorbent assay. Results: A total of 113 patients received ADSC treatment, and 75% (85/113) received ADSC injection at least twice with a 6-month interval between. No obvious abnormalities were observed in any patient after their first treatment; by contrast, 53% (45/85) of patients who received their second or third ADSC injection showed severe knee arthritis. IPP detected a common anti-15 kDa Ab in synovial fluid of 62% (8/13) of the samples analyzed from patients who showed severe arthritis. This Ab was not detected in synovial fluid obtained from the same joints before treatment. The corresponding autoantigen was identified as histone H2B. All available synovial samples from patients who tested positive for anti-histone H2B Ab were newly positive after the treatment; that is, none had been positive for anti-histone H2B Ab before treatment. Conclusions: Multiple ADSC injections for OA induced severe arthritis in a high percentage of patients, particularly after the second injection. Synovial fluid from some patients with knee arthritis contained Ab to histone H2B that appeared only after ADSC treatment. These findings provide new insights into the pathogenesis of ADSC treatment-induced severe arthritis.

Although reactive oxygen species (ROS) are known to have harmful effects in organisms, recent studies have demonstrated expression of ROS synthases at various parts of the organisms and the controlled ROS generation, suggesting possible involvement of ROS signaling in physiological events of individuals. However, physiological roles of ROS in the CNS, including functional roles in higher brain functions or neuronal activity-dependent ROS production, remain to be elucidated. Here, we demonstrated involvement of ROS – 8-NO2-cGMP signaling in motor learning and synaptic plasticity in the cerebellum. In the presence of inhibitors of ROS signal or ROS synthases, cerebellar motor learning was impaired, and the stimulus inducing long-term depression (LTD), cellular basis for the motor learning, failed to induce LTD but induced long-term potentiation (LTP)-like change at cerebellar synapses. Furthermore, ROS was produced by LTD-inducing stimulus in enzyme-dependent manner, and excess administration of the antioxidant vitamin E impaired cerebellar motor learning, suggesting beneficial roles of endogenous ROS in the learning. As a downstream signal, involvement of 8-NO2-cGMP in motor learning and cerebellar LTD were also revealed. These findings indicate that ROS – 8-NO2-cGMP signal is activated by neuronal activity and is essential for cerebellum-dependent motor learning and synaptic plasticity, demonstrating involvement of the signal in physiological function of brain systems.

Background/purpose: Tooth or bone regeneration requires large numbers of mesenchymal stem cells (MSCs). Although dental pulp is a suitable cell source, the number of MSCs present in this tissue is limited and they require a long period for regeneration. Therefore, the present study investigated vitamin B12 (Vb12) as an osteoinductive factor for MSCs obtained from dental pulp. Materials and methods: Dental pulp tissue was removed from the root canals of the extracted mandibular incisors of three 6-week-old male Fischer 344/N Slc rats using an endodontic file and whole cells were harvested. After the primary culture, cells were sub-cultured for calcified nodule formation in MEM containing dexamethasone (Dex), β-glycerophosphate (β-GP), vitamin C (Vc), and Vb12. Calcified nodules were confirmed under an inverted phase-contrast microscope. The alkaline phosphatase (ALP) activity of cells and quantity of Ca2+ in calcified nodules were measured. Results were analyzed using the Tukey-Kramer test. Results: Densely arranged calcified nodules were microscopically observed after the subculture of cells with Dex, β-GP, Vc, and Vb12. The ALP activity level was 0.077 ± 0.023 μmol/μg DNA in MEM supplemented with Vb12, which did not significantly differ from that without Vb12. A mass of calcium nodules formed in culture medium containing Dex, β-GP, Vc, and Vb12. The quantity of Ca2+ increased from 13.04 ± 0.44 to 20.91 ± 0.56 mg/dL (P

Background/purpose: In lower third molar (LM3) surgery, panoramic radiography (PAN) is important for the initial assessment of the anatomical association between LM3 and the inferior alveolar nerve (IAN). This study aimed to develop a deep learning model for the automated evaluation of the LM3–IAN association on PAN. Further, its performance was compared with that of oral surgeons using original and external datasets. Materials and methods: In total, 579 panoramic images of LM3 from 384 patients in the original dataset were utilized. The images were divided into 483 images for the training dataset and 96 for the testing dataset at a ratio of 83:17. The external dataset comprising 58 images from an independent institution was used for testing only. The LM3–IAN associations on PAN were categorized into direct or indirect contact based on cone-beam computed tomography (CBCT). The You Only Look Once (YOLO) version 3 algorithm, a fast object detection system, was applied. To increase the amount of training data for deep learning, PAN images were augmented using the rotation and flip techniques. Results: The final YOLO model had high accuracy (0.894 in the original dataset and 0.927 in the external dataset), recall (0.925, 0.919), precision (0.891, 0.971), and f1-score (0.908, 0.944). Meanwhile, oral surgeons had lower accuracy (0.628, 0.615), recall (0.821, 0.497), precision (0.607, 0.876), and f1-score (0.698, 0.634). Conclusion: The YOLO-driven deep learning model can help oral surgeons in the decision-making process of applying additional CBCT to confirm the LM3–IAN association based on PAN images.

Background: To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD. Objective: The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD. Methods: We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline. Results: We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses. Conclusion: We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.

The pathogenesis of non-alcoholic steatohepatitis (NASH) involves the simultaneous interaction of multiple factors such as lipid accumulation, oxidative stress, and inflammatory response. Here, the effect of human serum albumin (HSA) fused to thioredoxin (Trx) on NASH was investigated. Trx is known to have anti-oxidative, anti-inflammatory, and anti-apoptotic effects. However, Trx is a low molecular weight protein and is rapidly eliminated from the blood. To overcome the low availability of Trx, HSA-Trx fusion protein was produced and evaluated the therapeutic effect on high-fat diet (HFD)-induced NASH model mice. HSA-Trx administered before the formation of NASH pathology showed it to have a preventive effect. Specifically, HSA-Trx was found to prevent the pathological progression to NASH by suppressing lipid accumulation, liver injury markers, and liver fibrosis. When HSA-Trx was administered during the early stage of NASH there was a marked reduction in lipid accumulation, inflammation, and fibrosis in the liver, indicating that HSA-Trx ameliorates NASH pathology. The findings indicate that HSA-Trx influences multiple pathological factors, such as oxidative stress, inflammation, and apoptosis, to elicit a therapeutic benefit. HSA-Trx also inhibited palmitic acid-induced lipotoxicity in HepG2 cells. Taken together, these results indicate that HSA-Trx has potential as a therapeutic agent for NASH pathology.

Background: Nursing shortage is a global and priority issue. Affective commitment has been identified as a key to retention in the workplace. Exploring the way to promote the nurse's affective commitment is necessary to maintain the nursing workforce and care quality. The staff nurse's organizational justice (procedural and interactional justice) and the manager's condition of mental health have the potential to be related to the staff nurse's affective commitment. Objective: To explore the impact on the nurse's affective commitment from procedural and interactional justices at individual and unit levels and the manager's mental health. Design: A multi-site longitudinal design. Setting(s): Nine Japanese hospitals with more than 200 beds and located in an area with more than 150,000 people. Participants: 385 staff nurses and their 42 nurse managers who completed both surveys in 2016 and 2017. Methods: We analyzed the data from a two-year national survey of the Work Environment for hospital Nurses in Japan part II. Nurse staff and their managers completed the surveys. This multilevel analysis performed four random intercept models on affective commitment and entered the variables of procedural and interactional justices and manager mental health into the models. Results: The staff nurse's affective commitment was positively associated with procedural justice climate (unit level), interactional justice climate (unit-level), and the perception of interactional justice (individual justice). The manager's mental health (psychological distress) had a negative relationship with affective commitment. Conclusions: The climates of procedural and interactional justice, the individual perception of interactional justice, and the manager's mental health impacted the nurses’ affective commitment as a predictor of retention. Moreover, the perception of interactional justice and the organizational contexts (organizational justice climates and managers’ psychological distress) were mediated by affective commitment. Thus, support to maintain the manager's mental health is required to promote staff's affective commitment related to retention. Registration: None. Tweetable abstract: Nurse staff's affective commitment was stimulated by interactional justice, two types of organizational justice climate, and the manager's mental health.

Purpose: To report Vogt-Koyanagi-Harada (VKH) disease in a patient with extreme anisometropia. Observations: A 56-year-old woman was referred to our hospital. Her past medical history was significant for amblyopia in the right eye. At the initial visit, decimal best-corrected visual acuity (BCVA) was 0.03 (Snellen equivalent 5/160) in the right eye and 0.03 (Snellen equivalent 5/160) in the left eye, and axial length was 28.44 mm and 22.36 mm, respectively. Anterior chamber inflammation was seen predominantly in the right eye with fibrin exudates. Swept-source optical coherence tomography demonstrated choroidal thickening and folds predominantly in the left eye. Additionally, serous retinal detachment (SRD) was much more evident in the left eye than in the right eye. Subfoveal choroidal thickness (SCT) was 417 μm in the right and over 800 μm in the left eye. Cerebrospinal fluid examination revealed lymphocyte-dominant hypercellularity. Based on these findings, we diagnosed the patient with VKH disease and treated her with a high-dose systemic corticosteroid. One month after the initiation of treatment, SRD in both eyes fully resolved, and SCT decreased to 105 μm in the right and 311 μm in the left eye. Conclusions and Importance: The marked discrepancy in axial length between the right and left eyes might contribute to the different severity of inflammation in VKH disease.

The reversed halo sign (RHS) has been associated with various pulmonary diseases. We report a rare case of pulmonary mucosa-associated lymphoid tissue lymphoma forming a RHS from a ground-glass opacity (GGO). A 73-year-old man was followed-up for the GGO on his computed tomography images, which gradually extended peripherally. During the fourth year of follow-up, the GGO significantly evolved into a well-demarcated, oval lesion, with interlobular and intralobular septal thickenings, and multiple air spaces were surrounded by a well-defined thin consolidative rim, called the RHS. A pathologic study of the specimen via transbronchoscopic biopsy revealed pulmonary mucosa-associated lymphoid tissue lymphoma.

Background: and Purpose: As the number of international students from Belt and Road Initiative countries continues to increase in China, it is essential to find methods to improve cross-cultural adaptation in the host country, a crucial aspect of the experiences of international nursing students. Therefore, this study aimed to investigate the change in cross-cultural adaptation of international nursing students during the first year in China. Methods: Data collection was conducted for international nursing students (n = 108) between September 2019 and August 2020, focusing on sociocultural adaptation, academic adaptation, and academic performance of international nursing students using validated questionnaires. Results: The mean score at the follow-up time verified an increased level of sociocultural and academic adaptation and academic performance. Academic adaptation is a complete mediator between sociocultural adaptation and academic performance at two-time points, and the size of the mediation effect accounted for 95.9 % of the total effect in six months and 99.0 % in one year. Conclusions: The findings emphasized the importance of sociocultural and academic adaptation in cross-cultural adaptation and suggest that educational institutions should provide learning environments supporting these factors to ensure academic success.

Many studies have confirmed the memory enhancement effect of production, generation and elaboration which can be effective after only one encoding. It is also known that greater memory enhancement effects can be obtained by combining multiple memory strategies during encoding. This study aimed to investigate whether the combination of production and self-generated elaboration enhances memory performance compared with production or generation alone. A total of 23 undergraduate and graduate students participated in this study. In the functional magnetic resonance imaging analysis, we explored the neural representation of remembering information after production and self-generated elaboration strategy. We set four encoding strategy conditions: (1) Read Silent (read without production), (2) Read Aloud (only production), (3) Add Silent (self-generated elaboration without production), (4) Add Aloud (production and self-generated elaboration). The retrieval performance and brain activity while retrieving the learned sentences after a one-week delay were examined. The behavioral results showed that the highest memory performance was for sentences encoded in Add Aloud. The interaction between production and self-generated elaboration was statistically significant. These results suggest that the memory enhancement effect of combining production and self-generated elaboration is not a simple addition nor synergistic facilitation effect. The imaging results showed that the following areas were related to the retrieval of the target encoded in the add aloud condition: the area related to integration of internal and external information (precuneus), area related to information rich stimuli (lateral occipital lobe), area related to self-involvement and inference of others' feelings (MPFC), area related to seen imagery (retrosplenial region) and area related to adjustment of movement (cerebellum). These results suggest that with an encoding strategy that combines production and self-generated elaboration, integrated auditory input of vocalizations and generated images, visual images of the scene, self-relevance, inference of other's feeling, movement by moving mouth are stored with the target and enhanced memory performance of AA.

Summary: Lymphedema is a progressive condition accompanying cellulitis and angiosarcoma, suggesting its association with immune dysfunction. Lymphatic venous anastomosis (LVA) can provide relief from cellulitis and angiosarcoma. However, the immune status of peripheral T cells during lymphedema and post-LVA remains poorly understood. Using peripheral blood T cells from lymphedema, post-LVA, and healthy controls (HCs), we compared the profile of T cell subsets and T cell receptor (TCR) diversity. PD-1+ Tim-3 + expression was downregulated in post-LVA compared with lymphedema. IFN-γ levels in CD4+PD-1+ T cells and IL-17A levels in CD4+ T cells were downregulated in post-LVA compared with lymphedema. TCR diversity was decreased in lymphedema compared with HCs; such TCR skewing was drastically improved in post-LVA. T cells in lymphedema were associated with exhaustion, inflammation, and diminished diversity, which were relieved post-LVA. The results provide insights into the peripheral T cell population in lymphedema and highlight the immune modulatory importance of LVA.

Basement membranes (BMs) are thin, sheet-like extracellular structures that cover the basal side of epithelial and endothelial tissues and provide structural and functional support to adjacent cell layers. The molecular structure of BMs is a fine meshwork that incorporates specialized extracellular matrix proteins. Recently, live visualization of BMs in invertebrates demonstrated that their structure is flexible and dynamically rearranged during cell differentiation and organogenesis. However, the BM dynamics in mammalian tissues remain to be elucidated. We developed a mammalian BM imaging probe based on nidogen-1, a major BM-specific protein. Recombinant human nidogen-1 fused with an enhanced green fluorescent protein (Nid1-EGFP) retains its ability to bind to other BM proteins, such as laminin, type IV collagen, and perlecan, in a solid-phase binding assay. When added to the culture medium of embryoid bodies derived from mouse ES cells, recombinant Nid1-EGFP accumulated in the BM zone of embryoid bodies, and BMs were visualized in vitro. For in vivo BM imaging, a knock-in reporter mouse line expressing human nidogen-1 fused to the red fluorescent protein mCherry (R26-CAG-Nid1-mCherry) was generated. R26-CAG-Nid1-mCherry showed fluorescently labeled BMs in early embryos and adult tissues, such as the epidermis, intestine, and skeletal muscles, whereas BM fluorescence was unclear in several other tissues, such as the lung and heart. In the retina, Nid1-mCherry fluorescence visualized the BMs of vascular endothelium and pericytes. In the developing retina, Nid1-mCherry fluorescence labeled the BM of the major central vessels; however, the BM fluorescence were hardly observed in the peripheral growing tips of the vascular network, despite the presence of endothelial BM. Time-lapse observation of the retinal vascular BM after photobleaching revealed gradual recovery of Nid1-mCherry fluorescence, suggesting the turnover of BM components in developing retinal blood vessels. To the best of our knowledge, this is the first demonstration of in vivo BM imaging using a genetically engineered mammalian model. Although R26-CAG-Nid1-mCherry has some limitations as an in vivo BM imaging model, it has potential applications in the study of BM dynamics during mammalian embryogenesis, tissue regeneration, and pathogenesis.

Background/Objectives: This study examined the effects of a single and chronic oral intake of l-arginine supplementation on blood ammonia concentration and exercise performance. Methods: Sixteen healthy young men (mean ± standard deviation, 23 ± 3 years) participated in a randomised, double-blind, cross-over, placebo-controlled study. For the acute trials, the participants consumed 200 mL of water containing either l-arginine (5 g) or placebo (dextrin; 5.5 g) and performed cycling exercise at 75% of heart rate reserve for 60 min, followed by a 15-min cycling performance test. For the chronic trials, the participants continued to consume each designated supplement twice a day for another 13 days, and then repeated the same protocol as the acute trials at day 15. After a 14-day washout period, the participants changed the supplement and repeated the same protocol as above. Results: Plasma ammonia concentrations were lower in the chronic arginine trial than those in both acute placebo (mean difference - 4.5 μmol/L) and acute arginine (mean difference - 5.1 μmol/L) trials (p

In this study, we evaluated the photostability of a cocrystal of naproxen (NPX) and nicotinamide (NA) for the development of the photostabilization strategy. NPX photodegradation during ultraviolet-light (UV) irradiation was estimated by high-performance liquid chromatography (HPLC). The photostability of a NPX-NA cocrystal was less than NPX in the solid-state. Furthermore, NPX was photodegraded faster in the presence of NA at a higher concentration when the NPX-NA mixtures were UV-irradiated. The values of residual amounts of NPX in UV-irradiated NPX-NA cocrystal and mixture were 76.60 ± 3.85% and 70.06 ± 4.09%, respectively, which were significantly lower compared with that of UV-irradiated NPX powder (83.57 ± 2.15%). However, in the case that the effect of NA in the suspension of NPX was investigated, NA had no effect on NPX photodegradation. Residual amounts of NPX in UV-irradiated suspensions of NPX and NPX-NA cocrystal were comparable (33.13 ± 6.02% and 30.22 ± 2.09%, respectively). These results suggested that NA might promote NPX photodegradation only in the solid-state on account of that NA molecule could deliver the excitation energy to NPX molecule. This is the first study focused on the photochemical behavior of NPX-NA cocrystal and mixture and suggests that the presence of NA might induce the change of photostability of NPX in the powder form.

Background: Giant malignant tumors have an increased risk of intraoperative rupture, which might lead to a worse disease condition and tumor recurrence. We performed a clinical study on patients with a giant ovarian mass who underwent laparoscopy combined with an Aron Alpha method. Methods: This retrospective clinical study spanned from January 2016 to September 2022 and included 23 patients with giant ovarian tumors treated with an Aron Alpha method. Results: The mean age of the subjects was 47.6 ± 17.8 years, mean tumor diameter 20.4 ± 5.8 cm, mean surgical duration 87.2 ± 33.1 min, and mean hemorrhage volume 94.1 ± 92.2 mL. No patient experienced intraoperative tumor rupture or surgery-related symptoms. Histopathology of excised samples revealed serous cyst adenoma and mucinous cystadenoma, mucinous cystadenoma of borderline malignancy and mature cystic teratoma, and endometriotic cyst adenoma in 6, 4, and 3 patients, respectively. The mean hospitalization period was 6.0 ± 1.2 days, and the hospitalization period was not extended in any subject. Conclusion: The Aron Alpha method allows tumor resection without capsular rupture and is a useful, minimally invasive surgical method for resecting giant ovarian tumors in which malignancy cannot be ruled out.

We report the establishment of two human induced pluripotent stem cell (iPSC) lines from individuals without auditory disorders. Extensive audiometry tests were performed to confirm normal hearing. The generated iPSC lines expressed pluripotency genes and showed differentiation capability into the three germ layers. The iPSC lines will be used as controls for pathological analysis and drug screening for ear disorders.

ABSTRACT: Objectives: The extensive spread of colistin resistance represents an enormous concern to infectious disease treatment, because colistin is one of the few effective antibiotics against multidrug-resistant bacterial infections, including carbapenem-resistant bacteria. This dissemination can be caused by plasmid transfer containing the colistin resistance gene mcr. Therefore, the plasmid host range affects horizontal gene transfer. This study reports a fusion plasmid of different incompatibility types, which could easily expand the plasmid host range, allowing widespread mcr prevalence in the microbial community. Methods: Genome sequences of colistin-resistant Escherichia coli isolates from stool specimens of healthy human residents in Ecuador were determined using the DNBSEQ and MinION platforms. Hybrid genome assembly was performed using Unicycler, and the genomes were annotated using DFAST. Genome analysis was performed using the Geneious Prime software. Results: Two colistin-resistant E. coli strains isolated separately from different residents presented mcr-carrying plasmids with fused different incompatibility types, IncFIA, IncHIIA, and IncHIIB. The phylogenies of these host bacteria were different. The sizes of the mcr-carrying fusion plasmids pLR-06 and pLR-50 with the full Tn6330 mcr-transposon were 260 Kbp and 198 Kbp, respectively. Both fusion plasmids possessed other resistance genes, including tet(B), tet(M), blaTEM-1b, sul3, cmlA1, aadA1, aadA2, fosA3, and dfrA12. Conclusion: This is the first report of a fusion plasmid comprising different incompatibility types with mcr from colistin-resistant E. coli strains isolated from community residents. The mcr fusion plasmid may play a crucial role in achieving horizontal mcr transmission and the evolution of the multidrug resistance plasmid among hosts.

Summary: The relationships between tissue-resident microglia and early macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding in situ and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated or genetic labeling, we find that intraventricular CD206+ macrophages, which are abundantly observed along the inner surface of the mouse cerebral wall, frequently enter the pallium at embryonic day 12. Immunofluorescence of the tracked cells show that postinfiltrative macrophages in the pallium acquire microglial properties while losing the CD206+ macrophage phenotype. We also find that intraventricular macrophages are supplied transepithelially from the roof plate. This study demonstrates that the “roof plate→ventricle→pallium” route is an essential path for microglial colonization into the embryonic mouse brain.

Background: Even though female adolescents can get information regarding sexual and reproductive issues from different sources, parents are the preferred source of information for most adolescents. Objective: The study was aimed at assessing the parent-female adolescent communication regarding sexual and reproductive health issues in southwest Ethiopia. Method and materials: Community-based retrospective cross-sectional study design was employed among 388 parents of a female adolescent from May 5 to 26, 2021. The data were entered into Epi data version 4.2 and analyzed by the Statistical software package for social science version 23. Bivariable and multivariable logistic regressions were done to identify factors associated with poor parent-female adolescent communication regarding sexual and reproductive health issues. Results: According to this study, 223 (61.9%) parents had poor communication on sexual and reproductive health with their female adolescents. Having no communication difficulties regarding sexual and reproductive health issues[AOR = 0.287;95 %CI:0.167–0.494], poor knowledge of SRH issues[AOR = 2.082;95 %CI:1.222–3.547], in favorable attitude towards parents- female adolescent sexual and reproductive health communication[AOR = 1.847;95 %CI:1.065–3.204], parents didn’t have previous experience of sexual and reproductive health problem[AOR = 3.062;95 %CI:1.779–5.204], parents-whose female adolescent not asked about SRH issues[AOR = 0.434.;95 %CI:0.265–0.743] were the identified statically associated factors with poor parent-female adolescent communication regarding sexual and reproductive health issues. Conclusions: Despite the fact that poor parent–female adolescent communication has many impacts on sexual and reproductive health issues in female adolescents this study showed the status of poor parents-female adolescent communication regarding sexual and reproductive health issues was high. The knowledge, attitude, and communication challenges of parents regarding sexual and reproductive health concerns were found to be the identified factors associated with poor parents-female adolescent sexual and reproductive health communication practices. Thus, creating a positive atmosphere, and effective communication between parents and adolescents through empowering both parents and adolescents can improve the overall sexual and reproductive health issues of the adolescent.

The study on K-12 artificial intelligence (AI) education poses three challenges: ''(i) What topics in the machine learning (ML) process should be hidden from K-12 students?” '' (ii) How do you teach K-12 students the mathematical model behind the ML process?” and '' (iii) How does AI education influence the acceptance of AI technology?”. This paper addresses challenges (i) to (iii). We developed a machine learning role-playing game (ML-RPG) and had 166 participants from lower grades of elementary school to the elderly use it. Participants used ML-RPG to role-play the ML process of acquiring data, representing data with graphs, inferencing based on if-then rules, and optimizing parameters based on loss functions in the ML model. Challenge (i) was assessed using an achievement test. The results showed that the ML process of perception at K1-3, data representation and reasoning based on if-then rules at K4-6, and simple ML model learning and evaluation at K7+ can be unveiled. Challenge (ii), K7+ were able to understand the optimization process of the ML model by role-playing to minimize the loss function shown on the graph. Challenge (iii), it was shown that most people who feel vague anxiety and fear about AI change to a positive impression of AI due to the following three factors: (a) participants understanding the decision criteria of AI, (b) increased self-efficacy among participants, and (c) participants realizing that AI can be applied to familiar things.

A 2-year-old, male patient with a mediastinal cystic mass causing tracheal stenosis underwent complete resection of the mass via a partial median sternotomy. The risk of left recurrent laryngeal nerve (RLN) injury seemed high because the mass was located just between the trachea and the esophagus. To reduce the risk of injury to the RLN, intraoperative nerve monitoring (IONM) was used with an adhesive laryngeal electrode, which was wrapped around an endotracheal tube with a 4.0-mm inner diameter. Electromyography of the vocal cords was successfully performed, allowing the left RLN to be clearly detected intraoperatively. The patient's postoperative course was uneventful, and he had no postoperative symptoms of RLN palsy. Esophageal duplication cyst was pathologically diagnosed.IONM can be applied even to infants and may be very useful for improving procedural safety and avoiding damage to the RLN during rection of a mediastinal mass.

A 46-year-old man developed a right renal tumor with multiple lung and hilar lymph node metastases. Laparoscopic radical nephrectomy was performed, and clear cell renal cell carcinoma was diagnosed 6 years earlier. Despite the use of available systemic therapeutic agents, atelectasis in the right upper lobe due to a pulmonary hilar mass and brain metastases reduced his performance, and he was becoming terminally ill. After administration of avelumab plus axitinib as 9th-line therapy, significant shrinkage of the metastases and improvement in performance status were observed. This case indicates the possibility of using avelumab plus axitinib as late-line therapy.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. In the present study, we investigated TRP vanilloid subfamily member 2 (TRPV2) expression in lower oesophageal sphincter (LES) and its involvement in acid reflux oesophagitis in rats. Expression of TRPV2 and nerve growth factor mRNAs was significantly enhanced in LES of rats with reflux oesophagitis compared with normal rats. TRPV2 was mainly expressed in inhibitory motor neurons, and partly in intrinsic and extrinsic primary afferent neurons, and macrophages in LES of normal and reflux oesophagitis rats. Number of TRPV2-immunopositive nerve fibres was significantly increased, but that of nNOS-, CGRP-, and PGP9.5-nerve fibres was not changed in reflux oesophagitis compared with normal group. Probenecid produced nitric oxide production and relaxation in LES and this response was significantly enhanced in oesophagitis compared with normal group. Probenecid-induced relaxant effect was blocked by a TRPV2 inhibitor, tranilast, and a NOS inhibitor, NG-nitro-l-arginine methyl ester, in reflux oesophagitis rats. Oral administration of tranilast significantly improved body weight loss, oesophageal lesions, and epithelial thickness in oesophagitis model. These results suggest that up-regulation of TRPV2 in inhibitory motor neurons is involved in LES relaxation in oesophagitis model. TRPV2 inhibition might be beneficial for treatment of GERD.

Background/objective: Gum chewing while walking increases walking distance and energy expenditure in middle-aged male and female individuals. This study aimed to examine the effects of gum chewing while walking on walking distance and energy metabolism in male and female individuals of various age groups. Methods: Fifty participants (25 male and 25 female individuals) aged 22–69 years completed two trials in a random order. In the gum trial, participants walked at a natural pace for 15 min while chewing two gum pellets (1.5 g, 3 kcal per pellet) following a 50-min rest period. In the tablet trial, participants rested for 50 min before walking, and the participants then walked at a natural pace for 15 min after ingesting two pellets of tablet containing the same ingredients with the exception of the gum base. The walking distance, step count, walking speed, stride, heart rate, energy expenditure, and respiratory exchange ratio were measured. Results: Walking distance, step count, walking speed, heart rate, and energy expenditure during walking were significantly higher in the gum trial than in the tablet trial. In participants aged ≥40 years, walking distance, walking speed, stride, heart rate, and energy expenditure during walking were significantly increased during the gum trial compared with those during the tablet trial. Conclusion: The study findings demonstrated that gum chewing while walking increased walking distance and energy expenditure in both male and female individuals.

We performed clinical retrospective study in female cancer patients and fundamental experiments in mice, in order to clarify risk factors for paclitaxel-induced peripheral neuropathy (PIPN). In the clinical study, 131 of 189 female outpatients with cancer undergoing paclitaxel-based chemotherapy met inclusion criteria. Breast cancer survivors (n = 40) showed significantly higher overall PIPN (grades 1–4) incidence than non-breast cancer survivors (n = 91). Multivariate sub-analyses of breast cancer survivors showed that 57 years of age or older and endocrine therapy before paclitaxel treatment were significantly associated with severe PIPN (grades 2–4). The age limit was also significantly correlated with overall development of severe PIPN. In the preclinical study, female mice subjected to ovariectomy received repeated administration of paclitaxel, and mechanical nociceptive threshold was assessed by von Frey test. Ovariectomy aggravated PIPN in the mice, an effect prevented by repeated treatment with 17β-estradiol. Repeated administration of thrombomodulin alfa (TMα), known to prevent chemotherapy-induced peripheral neuropathy in rats and mice, also prevented the development of PIPN in the ovariectomized mice. Collectively, breast cancer survivors, particularly with postmenopausal estrogen decline and/or undergoing endocrine therapy, are considered a PIPN-prone subpopulation, and may require non-hormonal pharmacological intervention for PIPN in which TMα may serve as a major candidate.

Background/Objective: This study examined the chronic effect of increased physical activity on postprandial triglycerides in older women. Methods: Twenty-six women, aged 72 ± 5 years (mean ± SD), participated in this study. Participants in the physical activity group (n = 11) were asked to increase their activities above their usual lifestyle levels for 12 weeks. Participants in the control group (n = 15) maintained their usual lifestyle for 12 weeks. All participants rested and consumed a standardized breakfast after a 24-h period of physical activity avoidance at baseline, 4 weeks, and 12 weeks. Blood samples were collected in the fasted state (0 h) and at 2, 4, and 6 h after breakfast. Results: The average increased time spent in self-selected activities per day was 1.1 ± 19.3 min over the 12 weeks compared with the baseline in the physical activity group. There was no difference in the postprandial time-averaged triglyceride area under the curve at baseline (1.59 ± 0.81 vs. 1.39 ± 0.67 mmol/L, p = 0.515) or over the 12-week intervention (1.78 ± 1.00 vs. 1.31 ± 0.67 mmol/L, p = 0.212) between the physical activity and control groups. Conclusion: Postprandial triglyceride concentrations were not reduced after performing self-selected activities under free-living conditions in older women when these responses were determined 24 h after the last physical activity bout. (Trial registration ID: UMIN000037420).

Proteins interacting with G protein-coupled receptors (GPCRs) can modulate signal transduction of these receptors. However, the regulatory mechanisms of the interacting proteins are diverse and largely unknown. We have previously shown that Tctex-1 (or DYNLT1) can interact with the parathyroid hormone receptor (PTHR). In the present study, we investigated the role of Tctex-1 in the PTHR signaling and found that Tctex-1 augmented the PTHR-mediated Gs/adenylyl cyclase (AC) pathway by activating AC regardless of the binding to PTHR. Furthermore, Tctex-1 directly bound to AC type 6. These data demonstrate a novel mechanism underlying GPCR/Gs signaling regulated by Tctex-1.

We describe a dementia patient with comorbid recurrent cellulitis and lymphedema in the left lower limb who was treated successfully for recurrent cellulitis by lymphaticovenular anastomosis (LVA). The patient, an 83-year-old woman, suffered from recurrent cellulitis three times a year on average for 15 years. Compression therapy was impossible because of dementia. After LVA, there has been no recurrence of cellulitis for 2 years.It is difficult to administer decongestive lymphatic therapy in some patients, such as patients with dementia. LVA is a promising treatment for recurrent cellulitis in a dementia patient with lymphedema.

We investigated whether benzothiazepines could produce anxiolytic effects via allopregnanolone (ALLO) biosynthesis in mice. We compared the behavioral effects caused by benzothiazepines to those caused by carbamazepine and sodium valproate. We found that a pretreatment with finasteride (a 5 alpha-reductase inhibitor) suppressed carbamazepine-induced anxiolytic effects but not the effects of sodium valproate. Similar to carbamazepine, diltiazem and JTV-519 displayed anxiolytic effects that were suppressed by a pretreatment with finasteride. We clearly demonstrate that the benzothiazepines, diltiazem and JTV-519, exert an anxiolytic-like effect via ALLO biosynthesis in mice.

Primary rhabdomyosarcoma (RMS) of the diaphragm, especially alveolar RMS, is extremely rare. Because of its rarity, no treatment for it has yet been established, but previous studies have reported long-term survival in recipients of a combination therapy with local control, including a total resection and/or radiation therapy concomitant with multiagent chemotherapy. We experienced a case of primary alveolar rhabdomyosarcoma of the diaphragm surrounding the gastric cardia in a 15-year-old, female patient. After administering chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide (VAC) to shrink the tumor, tumor resection was performed with a proximal gastrectomy and partial resection of the diaphragm, pericardium, and left lung. After receiving postoperative adjuvant chemotherapy with VAC and radiotherapy at a total of 41.4 Gy, the patient has been relapse-free for 18 months. The tumor-induced stenosis at the hilum was corrected, allowing oral intake and markedly improving the patient's nutritional status. Tumor resection with a proximal gastrectomy for primary diaphragmatic RMS surrounding the lower esophagus is recommended both for its efficacy in local control and for allowing the preservation of postoperative gastrointestinal function.

Purpose: Exposure keratopathy often progresses even with conventional various treatments and needs plastic surgery. However, plastic surgery of eye lid is often difficult in cases with poor general condition by cerebrovascular disorders. We will propose a novel method using synthetic rubber sheet to manage the exposure keratopathy under poor general conditions. Observations: We treated with synthetic rubber sheet on 9 eyes of 9 patients who suffered from refractory exposure keratopathy due to cerebrovascular disorders. Sheets cut from sterile surgical gloves made of synthetic rubber (SR sheets) were placed directly onto the ocular surface with antibiotic ointment and fixed with gauze and tape. Severity of the exposure keratopathy was scored before and after the application of SR sheet. Covered ocular surface with SR sheet could keep an adequate moist environment and exposure keratopathy was improved in all the cases with no adverse effects during an average observation period of 166.2 days. Conclusions and importance: Sterile synthetic rubber sheet cut from surgical gloves is an effective, safe, easy, and economical material to maintain better condition of ocular surface and especially useful for refractory exposure keratopathy under poor general condition.

Purpose: To report a case of branch retinal vein occlusion (BRVO) in which rapid formation of macular pucker was observed after an intravitreal ranibizumab (IVR) injection. Observations: A 66-year-old patient was referred to our department for the treatment of macular edema (ME) secondary to BRVO in the left eye. On the initial visit, widespread retinal hemorrhage was observed around the superior temporal vascular arcade, and the decimal best-corrected visual acuity (BCVA) was 0.7 (Snellen equivalent 20/29) in the left eye. Optical coherence tomography demonstrated a thin epiretinal membrane (ERM) accompanied by diffuse retinal thickening. A 0.5 mg IVR injection was administered for the treatment of ME and prompt resolution of retinal hemorrhage. Fourteen days after IVR administration, the ERM had progressed remarkably into a macular pucker and had spread from the superior macula to the equator, accompanied by partial tractional retinal detachment. We performed pars plana vitrectomy combined with encircling scleral buckling. Three months after the surgery, the decimal BCVA was 0.4 (Snellen equivalent 20/50), the retina was attached, and no recurrence of ME or proliferation was observed. Conclusions and Importance: IVR for BRVO may cause rapid formation of macular pucker in the eye, especially in the presence of pre-existing ERM. Careful observation of patients with BRVO is essential after administration of anti-VEGF agents, especially in eyes with pre-existing ERM.