Profiles of psychological flexibility and caregiving experience in dementia family caregivers: A latent profile analysis.

OBJECTIVES: To explore the profiles of psychological flexibility among dementia family caregivers and examine their associations with psychological well-being and caregiving factors. METHODS: Participants were 521 dementia family caregivers in Japan. Latent profile analysis was conducted to explore the profiles of psychological flexibility. The analyses examined differences in depression, anxiety, life satisfaction, and work-family conflict/enrichment between the profiles, and whether sociodemographic variables and caregiving stressors predict the profile. RESULTS: Four distinct profiles were identified: high psychological flexibility (14.2%), moderate psychological flexibility with high commitment (24.7%), moderate psychological flexibility with low commitment (48.0%), and low psychological flexibility (13.1%). The low psychological flexibility profile exhibited the highest scores of depression, anxiety and work-family conflict, followed by the moderate psychological flexibility with low/high commitment profiles, and the high psychological flexibility profile. The high psychological flexibility and moderate psychological flexibility with high commitment profiles exhibited higher life satisfaction than the moderate psychological flexibility with low commitment profile. Caregiving stressors, marital status, and caregiver status predicted the profile. CONCLUSION: Enhancing defusion and acceptance, rather than increasing commitment to personal values, may be beneficial in supporting distressed caregivers. Having more caregiving stressors, being single/divorced/bereaved, and being a primary caregiver may be useful indicators of decreased psychological flexibility among dementia family caregivers.

Family Carers of People with Dementia in Japan, Spain, and the UK: A Cross-Cultural Comparison of the Relationships between Experiential Avoidance, Cognitive Fusion, and Carer Depression.

Objective and research design This study investigated whether the relationship between experiential avoidance and carer depression is mediated by cognitive fusion using path analysis and whether this model differs between family carers from Japan, Spain, and the UK using multi-group path analysis. Results The whole sample model (N = 745) showed a good fit to the data. The direct effect of experiential avoidance on carer depression (ß = .10) and its indirect effect on carer depression through cognitive fusion (ß = .15) were significant. Examined variables accounted for 45% of the variance of depression. Multi-group path analysis confirmed the same pattern of indirect path across 3 countries, while the direct path was no longer significant in Spanish and UK samples.Conclusion These findings suggest that targeting cognitive fusion may be particularly critical in culturally diverse carers and pre-emptive efforts to reduce experiential avoidance using psychological techniques may be beneficial among family carers prone to cognitive fusion regardless of cultural differences.

Reliability and validity of the Japanese version of the Valued Living Questionnaire Adapted to Caregiving.

OBJECTIVES: This study developed the Japanese version of the Valued Living Questionnaire Adapted to dementia Caregiving (J-VLQAC) and assessed its reliability and validity. METHODS: A 2-wave longitudinal survey with an interval of two weeks was conducted with Japanese dementia family caregivers (n = 521 at T1; n = 424 at T2). RESULTS: Confirmatory factor analysis demonstrated a poor fit to our data for the original 2-factor model. Exploratory factor analysis resulted in a new 3-factor model (i.e., Own Values, Family Values, and Health Values). Both models showed similar good internal consistency (Cronbach's alpha) and test-retest reliability. Significant correlations between the J-VLQAC and the Valuing Questionnaire (VQ) and measures assessing related constructs (e.g., cognitive fusion) supported good criterion validity and acceptable level of construct validity for both models. Compared to the original 2-factor model, the new 3-factor model showed higher incremental validity, which was assessed through the hierarchical regression analysis examining whether the J-VLQAC predicts depression, anxiety, and life satisfaction over and above the VQ. CONCLUSIONS: The J-VLQAC has good reliability and acceptable validity. CLINICAL IMPLICATIONS: The information gathered from the J-VLQAC can be used to tailor psychological support and help caregivers engage in activities that reflect their personal values.

[A Case of Sclerosing Angiomatoid Nodular Transformation Resected for Suspected Relapse of Diffuse Large B-cell Lymphoma].

We report a case of sclerosing angiomatoid nodular transformation(SANT)5 years after remission of diffuse large B-cell lymphoma(DLBCL). A 64-year-old woman was diagnosed a nodular mass at the spleen by a contrast-enhanced CT scan 5 years after the relief for DLBCL. The mass showed accumulation of FDG. Because the possibility of the recurrence of malignant lymphoma could not be ruled out, laparoscopic splenectomy was performed for diagnosis and treatment. Immunohistologically, the resected mass revealed 3 different vascular components pattern(CD31, CD34 and CD8), so we diagnosed SANT. It is difficult to distinguish from malignant lymphoma or cancer even with various examination, so laparoscopic splenectomy is useful for diagnosis and treatment.

Does global warming decrease the correlation between cherry blossom flowering date and latitude in Japan?

In Japan, the geographical distribution of the first date of flowering (FFD) of Yoshino cherry trees (Cerasus ×yedoensis) in 2020, a year when temperatures were mild during the previous December and March, was different from the average FFD, which progresses northward along a latitudinal gradient. We hypothesized that global warming may have changed the average geographical pattern of the FFD. To test this hypothesis, we examined the relationship between the observed FFD and latitude at 42 sites during the period 1953-2020. We found that the correlation between FFD and latitude had decreased since 1980. This decrease may have been caused by a rise of temperatures in winter that delayed dormancy release and the subsequent FFD in areas where the annual mean temperature is high. Our results suggest that the correlation between FFD and latitude will decrease further as the climate warms in the future.

Stress-buffering Effect of Coping Strategies on Interrole Conflict among Family Caregivers of People with Dementia.

OBJECTIVES: To examine the stress-buffering effect of coping strategies on the adverse effects of interrole conflict on the mental health of employed family caregivers, and clarify the moderating role of attentional control on this stress-buffering effect. METHODS: Data were drawn from a two-wave longitudinal online survey of employed Japanese family caregivers of people with dementia (263 males, 116 females; age 51.54 ± 9.07 years). We assessed interrole conflict, coping strategies, attentional control, mental health variables (psychological strain and quality of life), and confounding factors. RESULTS: Hierarchical regression analyses controlled for sociodemographic factors found formal support seeking had a stress-buffering effect for strain- and behavior-based caregiving interfering with work (CIW) only on psychological strain, and was moderated by attentional control. Single slope analysis showed higher CIW was related to higher psychological strain in those with greater use of formal support seeking and lower attentional control, but not in those with higher attentional control. CONCLUSIONS: Greater use of formal support seeking weakens the adverse effects of strain- and behavior-based CIW on psychological strain in people with high attentional control. CLINICAL IMPLICATIONS: Attentional control is a key factor in the stress-buffering effect of formal support seeking on strain- and behavior-based CIW.

Mechanistic insights into topical tacrolimus for the treatment of atopic dermatitis.

More than 15 years have passed since the clinical launch of topical tacrolimus for the treatment of atopic dermatitis. Its efficacy and safety have been clearly demonstrated in many global and domestic short-term and long-term clinical trials. Although the prolonged external application of steroids causes many adverse reactions including cutaneous atrophy, no such reactions occur with the use of topical tacrolimus. Therefore, the therapeutic guidelines recommend a combined topical treatment with tacrolimus and steroids. Tacrolimus is a potent immunosuppressant. However, recent studies have revealed its diverse action on the cardinal pathomechanisms of atopic dermatitis. In this review, we summarize the mechanistic role of tacrolimus in various aspects of allergic inflammation including mast cell activation, innate allergic response, pruritus, sensory nerve activation, and skin barrier dysfunction.

Can self-efficacy ameliorate interrole conflict among employed family caregivers? A moderated mediation approach.

OBJECTIVES: This study examined the moderation effect of different dimensions of self-efficacy on the way in which various types of interrole conflict mediate between caregiving demands and the mental health of employed family caregivers. METHOD: Using a moderated mediation approach, we examined the moderation effect of self-efficacy on interrole conflict's mediation between caregiving demands and mental health (psychological strain and quality of life) in a sample of Japanese employed family caregivers who regularly provide care at home (263 males aged 53.14 ± 8.28 years and 116 females aged 47.92 ± 9.77 years). RESULTS: Increased self-efficacy in managing dementia and in self-care were correlated with lower caregiving demands and better mental health among family caregivers. Self-efficacy in managing dementia was also positively correlated with increased interrole conflict. Increased caregiving demands were related to higher psychological strain in those with higher (+1SD), but not lower (-SD) self-efficacy in managing dementia. CONCLUSION: Self-efficacy does not play a protective role in managing the effect of caregiving demands on interrole conflict. It also does not appear to protect against any indirect effects of caregiving demands on the mental health of employed family caregivers.

8-(3-chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as potent and selective phosphodiesterase 5 inhibitors.

A novel series of highly selective phosphodiesterase 5 (PDE5) inhibitors was found. 8H-Pyrido[2,3-d]pyrimidin-7-one derivatives bearing an (S)-2-(hydroxymethyl)pyrrolidin-1-yl group at the 2-position and a 3-chloro-4-methoxybenzyl group at the 8-position exhibited potent PDE5 inhibitory activities and high PDE5 selectivity over PDE6. Among the synthesized compounds, the 5-methyl analogue (5b) showed the most potent relaxant effect on isolated rabbit corpus cavernosum with an EC30 value of 0.85 nM.

Design and synthesis of novel 5-(3,4,5-trimethoxybenzoyl)-4-aminopyrimidine derivatives as potent and selective phosphodiesterase 5 inhibitors: scaffold hopping using a pseudo-ring by intramolecular hydrogen bond formation.

5-(3,4,5-Trimethoxybenzoyl)-4-amimopyrimidine derivatives were found as a novel chemical class of potent and highly selective phosphodiesterase 5 inhibitors. A pseudo-ring formed by an intramolecular hydrogen bond constrained the conformation of 3-chloro-4-methoxybenzylamino and 3,4,5-trimethoxybenzoyl substituents and led to the discovery of T-6932 (19a) with a potent PDE5 inhibitory activity (IC50 = 0.13 nM) and a high selectivity over PDE6 (IC50 ratio: PDE6/PDE5 = 2400). Further modification at the 2-position of T-6932 resulted in the finding of 26, which exhibited potent relaxant effects on isolated rabbit corpus cavernosum (EC30 = 11 nM) with a high PDE5 selectivity over PDE6 (IC50 ratio: PDE6/PDE5 = 2800).

The discovery of avanafil for the treatment of erectile dysfunction: a novel pyrimidine-5-carboxamide derivative as a potent and highly selective phosphodiesterase 5 inhibitor.

Novel pyrimidine-5-carboxamide derivatives bearing a 3-chloro-4-methoxybenzylamino group at the 4-position were identified as potent and highly selective phosphodiesterase 5 inhibitors. Among them, we successfully found 10j (avanafil) which exhibited a potent relaxant effect on isolated rabbit cavernosum (EC30=2.1 nM) and a high isozyme selectivity.

Sociocultural beliefs, as well as goodness of fit, influence the effectiveness of coping in Japanese workers.

BACKGROUND: Although the goodness-of-fit hypothesis (GOFH) is one of the most important theories in research about the effect of coping on distress related to different stressful situations, there has been a mixed response to it in the literature. PURPOSE: The present study examined whether the effect of the sociocultural context in stressful situations is consistent with the GOFH. The study investigated sociocultural beliefs about the appropriateness of different coping strategies in a given group as the sociocultural context. METHOD: Japanese employees (N = 1,156) of an information technology company reported their appraisal of stressors' controllability, the coping strategies they employed for the stressors, their sociocultural beliefs about coping strategies, and their psychological distress in response to the stressors. RESULTS: The GOFH was supported only for problem-focused coping with task stressors and not for interpersonal stressors. The applicability of the GOFH differed by sociocultural beliefs about coping, namely an appraisal of what coworkers might think about the appropriateness of the coping method. CONCLUSION: These results suggest that it is important for managing stress to consider the sociocultural context as well as the GOFH.

Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients.

BACKGROUND: Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. METHODS: This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. RESULTS: Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history (P < .001), and preoperative hemoglobin level (P = .007) were related to HCC development, and the presence of HCC history (P = .002) and preoperative hemoglobin level (P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). DISCUSSION: The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

Analysis of Acquisition of COVID-2019 Neutralizing Antibodies in Organ Transplant Recipients.

BACKGROUND: This study confirmed the kinetics of antibodies acquired by SARS-CoV-2 vaccination in solid-organ transplant recipients and examined their association with the development of COVID-19 and immunosuppressive status in organ transplant recipients. METHODS: We measured COVID-19 neutralizing antibody titer in 21 organ transplant recipients vaccinated with the COVID-19 vaccine and 14 nontransplant recipients (control group) 3 times before and at 1 and 6 months after the third dose of vaccine. By confirming the kinetics of the acquired antibodies, we examined the relevance of the background characteristics of organ transplant recipients, such as the development of infectious diseases and immunosuppressive status. RESULTS: The proportion of patients with neutralizing antibodies was significantly higher in the nontransplant group than in the transplant group. Neutralizing antibody titers were significantly lower in transplant recipients when they were compared before the third dose and 1 month later. In the transplant recipient group, 11 patients were positive, and 10 were negative for neutralizing antibodies. When the causal relationship between the neutralizing antibody titer and background was examined, a positive correlation was found between the antibody titer and the number of years since transplantation, and a negative correlation was found between the tacrolimus trough values, amount of mycophenolate mofetil or steroids taken internally, and antibody titer. CONCLUSION: This study suggests that the effectiveness of vaccination in transplant recipients is associated with the post-transplant period before vaccination and the dose of immunosuppressive agents.

Acceptance and commitment improve the work-caregiving interface among dementia family caregivers.

Although working dementia family caregivers experience negative (i.e., work-family conflict; WFC) and positive (i.e., work-family enrichment; WFE) aspects of balancing work and caregiving, little is known about factors that alleviate negative aspects and enhance positive aspects of the work-caregiving interface. The purpose of this study was to examine the moderating effect of acceptance and commitment to personal values, which are transdiagnostic in nature and key concepts of acceptance and commitment therapy, on the relationships between work/caregiving demands and WFC and between work/caregiving resources and WFE among working dementia family caregivers. Data were drawn from a three-wave 6-month interval longitudinal survey of Japanese working dementia family caregivers (N = 747). Hierarchical linear modeling was used to examine the main effect of acceptance and commitment to personal values on WFC/WFE, and their moderating effect on relationships between work/caregiving demands and WFC, and work/caregiving resources (job control, supervisor/coworker support, organizational support, caregiving support) and WFE. Acceptance was negatively associated with WFC and weakened the positive relationship between work/caregiving demands and WFC. Commitment to personal values was negatively associated with WFC and positively associated with WFE. Commitment to personal values weakened the positive relationships between work/caregiving demands and WFC and moderated the relationship between caregiving support and WFE. The findings suggest that acceptance may be effective in alleviating WFC and commitment to personal values contributes to alleviating WFC and increasing WFE. Acceptance and commitment therapy may help to improve the work-caregiving interface among dementia family caregivers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Role of FK506-sensitive signals in asthmatic lung inflammation.

Asthma is airway inflammatory diseases caused by the activation of group 2 innate lymphoid cells (ILC2s) and type 2 helper T (TH2) cells. Cysteine proteases allergen cause tissue damage to airway epithelial cells and activate ILC2-mediated type 2 airway inflammation. FK506 is an immunosuppressive agent against calcium-dependent NFAT activation that is also effective against asthmatic inflammation. However, the effects of FK506 on cysteine protease allergen-mediated airway inflammation remain unclear. In this study, we investigated the suppressive effects of FK506 on airway inflammation. FK506 had a partial inhibitory effect on ILC2-dependent eosinophil inflammation and a robust inhibitory effect on T cell-dependent eosinophil inflammation in a cysteine protease-induced mouse asthma model. The infiltration of T1/ST2+ CD4 T cells in the lungs contributed to the persistence of eosinophil infiltration in the airway; FK506 completely inhibited the infiltration of T1/ST2+ CD4 T cells. In the initial phase, FK506 treatment targeted lung ILC2 activation induced by leukotriene B4 (LTB4)-mediated calcium signaling, but not IL-33 signaling. FK506 also inhibited the IL-13-dependent accumulation of T1/ST2+ CD4 T cells in the lungs of the later responses. These results indicated that FK506 potently suppressed airway inflammation by targeting ILC2 activation and T1/ST2+ CD4 T cell accumulation.

Antecedents and Outcomes of Enrichment Among Working Family Caregivers of People With Dementia: A Longitudinal Analysis.

OBJECTIVES: Despite evidence of negative aspects of the work-caregiving interface (e.g., work-family conflict) among family caregivers of people with dementia (PWD), little is known about the positive aspects (e.g., enrichment). We examined antecedents and outcomes of family-to-work enrichment (FWE) and work-to-family enrichment (WFE) among working family caregivers of PWD. In terms of antecedents, we investigated whether factors that alleviated work-family conflict increased enrichment. METHOD: We conducted a 3-wave 6-month-interval longitudinal online survey of Japanese working family caregivers of PWD (N = 747). We examined the mediational effects of WFE and FWE on associations between participants' work resources (job control, supervisor support, co-worker support, and organizational support) and caregiving support and their well-being (psychological distress and quality of life). We also examined the moderating effect of caregiving self-efficacy on the relationships between caregiving support/caregiving demands and FWE. RESULTS: Our longitudinal analysis confirmed supervisor support had a positive effect on WFE. FWE had no significant longitudinal mediating effect on the association between caregiving support and well-being, and self-efficacy had no longitudinal moderating effect on FWE. DISCUSSION: Supervisor support is important for WFE, but greater enrichment does not necessarily improve family caregiver well-being. Caregiving experience (i.e., caregiving demands and caregiving support) has little effect on the work-caregiving interface. Policy makers should focus on supporting companies to create family-friendly work environments. More research is needed on factors that increase FWE and moderate the relationship between enrichment and working family caregivers' well-being.

Clinical complete response after nivolumab administered as a third-line treatment for unresectable advanced gastric cancer with peritoneal dissemination: A case report.

INTRODUCTION AND IMPORTANCE: Nivolumab, which is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has been recommended as a third-line treatment based on the results of the ATTRACTION-2 study involving patients with unresectable advanced gastric cancer. CASE PRESENTATION: A 69 year-old woman was referred to our department with a diagnosis of gastric cancer based on an upper gastrointestinal endoscopy during a medical examination. The endoscopy, along with various tests, helped establish a diagnosis of unresectable advanced gastric cancer (cT4aN3aM1P1c, cStage IV) with peritoneal dissemination. The first and second-line chemotherapy administered was S-1 plus oxaliplatin followed by ramucirumab and nab-paclitaxel, respectively. In this case, the disease was evaluated as progressive disease due to increased peritoneal dissemination. Nivolumab was administered as the third-line treatment. The patient developed interstitial pneumonia after nine courses of nivolumab, for which chemotherapy was discontinued and prednisolone treatment was initiated. The patient had a complete response to treatment endoscopically, 9 months after the last administration of nivolumab. After that, there was no recurrence of the cancer, despite there being no treatment for 5 months. CLINICAL DISCUSSION: It was suggested that the therapeutic effect of nivolumab could be maintained for a long period after discontinuation of its administration. In addition, a correlation has been reported between the treatment efficacy and immune-related adverse events associated with nivolumab. CONCLUSIONS: The synergistic effect of the sustained effect of nivolumab and later-line treatment may contribute to the prolongation of survival after discontinuation of nivolumab in patients who are refractory or intolerant to treatment.

Obliteration of a Portosystemic Shunt by Hybrid Interventional Radiology Using a Transmesenteric Approach Under Minilaparotomy After Liver Transplantation: A Case Report.

Hepatic encephalopathy that occurs long after liver transplantation (LT) is an uncommon condition. Here, we describe the successful case of a 65-year-old patient who underwent interventional radiology (IVR) using a transmesenteric approach under minilaparotomy for hepatic encephalopathy because of a portosystemic shunt 11 years after ABO-incompatible living donor LT with splenectomy. Enhanced computed tomography confirmed a huge portosystemic shunt and left gastric vein (LGV)-esophageal-azygos vein, which was not treated during LT. Liver stiffness measurements based on transient elastography did not show severe fibrosis in the liver graft. Since the hyperammonemia could not be managed with conventional medical treatment, balloon-occluded retrograde transvenous obliteration (BRTO) was indicated. However, it was difficult to perform because the drainage vein could not be approached from the inferior vena cava (IVC). Surgical shunt ligation was also difficult because of the history of multiple laparotomies. Although intraperitoneal adhesion was severe, the portosystemic shunt was successfully embolized with metallic coils and a plug by IVR using a transmesenteric approach under minilaparotomy. No complications occurred during the operation. His symptoms improved after the operation. The ammonia level and portal flow by ultrasound also improved. He was discharged 14 days after surgery without any complications.

Tacrolimus ointment for the treatment of adult and pediatric atopic dermatitis: Review on safety and benefits.

Atopic dermatitis (AD) requires long-term management, mainly with topical anti-inflammatory agents. Topical corticosteroids (TCS) and tacrolimus ointment (TAC-O) are recommended as first-line treatments for AD. However, the long-term use of TCS is limited by cutaneous adverse events such as skin atrophy. For TAC-O, Japanese and US labelings were updated in 2003 and 2006, respectively, to include a boxed warning about a theoretical risk of skin cancer and lymphoma in patients treated with topical calcineurin inhibitors. However, TAC-O has been used worldwide for longer than 15 years to treat adult and pediatric patients with AD. Available data suggest that TAC-O is effective and well tolerated, and can improve quality of life. TAC-O has successfully been used in the proactive management of AD consisting of long-term intermittent use to prevent, delay or reduce the occurrence of AD flares. Systemic drug absorption after TAC-O application is negligible and unlikely to result in systemic immunosuppression. There is currently no strong evidence of an increased rate of malignancy in treated patients, and observational data from postmarketing surveillance studies have shown no safety concerns. In the absence of robust evidence, the warning about the carcinogenic potential in the Japanese labeling for TAC-O does not appear justified and should be reconsidered. This mitigation of description would allow adult and pediatric patients with AD to receive the effective treatment more appropriately.