Sex differences in symptom presentation and their impact on diagnostic accuracy in Werner syndrome.

AIM: Whether sex differences exist in hereditary progeroid syndromes remains unclear. In this study, we investigated sex differences in patients with Werner syndrome (WS), a model of human aging, using patient data at the time of diagnosis. METHODS: The presence of six cardinal signs in the diagnostic criteria was retrospectively evaluated. RESULTS: We found that the percentage of patients with all cardinal signs was higher in males than in females (54.2% vs. 21.2%). By the age of 40 years, 57.1% of male patients with WS presented with all the cardinal signs, whereas none of the female patients developed all of them. In particular, the frequency of having a high-pitched, hoarse voice, a characteristic of WS, was lower in female patients. The positive and negative predictive values for clinical diagnosis were 100% for males and females, indicating the helpfulness of diagnostic criteria regardless of sex. More female patients than male (86.7% vs. 64%) required genetic testing for their diagnosis because their clinical symptoms were insufficient, suggesting the importance of genetic testing for females even if they do not show typical symptoms of WS. Finally, the frequency of abnormal voice was lower in patients with WS harboring the c.3139-1G > C homozygous mutation. CONCLUSION: These results indicate, for the first time, that there are sex differences in the phenotypes of hereditary progeroid syndromes. The analysis of this mechanism in this human model of aging may lead to the elucidation of sex differences in the various symptoms of normal human aging. Geriatr Gerontol Int 2024; 24: 161-167.

Senescence-associated inflammation and inhibition of adipogenesis in subcutaneous fat in Werner syndrome.

Werner syndrome (WS) is a hereditary premature aging disorder characterized by visceral fat accumulation and subcutaneous lipoatrophy, resulting in severe insulin resistance. However, its underlying mechanism remains unclear. In this study, we show that senescence-associated inflammation and suppressed adipogenesis play a role in subcutaneous adipose tissue reduction and dysfunction in WS. Clinical data from four Japanese patients with WS revealed significant associations between the decrease of areas of subcutaneous fat and increased insulin resistance measured by the glucose clamp. Adipose-derived stem cells from the stromal vascular fraction derived from WS subcutaneous adipose tissues (WSVF) showed early replicative senescence and a significant increase in the expression of senescence-associated secretory phenotype (SASP) markers. Additionally, adipogenesis and insulin signaling were suppressed in WSVF, and the expression of adipogenesis suppressor genes and SASP-related genes was increased. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), alleviated premature cellular senescence, rescued the decrease in insulin signaling, and extended the lifespan of WS model of C. elegans. To the best of our knowledge, this study is the first to reveal the critical role of cellular senescence in subcutaneous lipoatrophy and severe insulin resistance in WS, highlighting the therapeutic potential of rapamycin for this disease.

Metabolomic analysis of serum samples from a clinical study on ipragliflozin and metformin treatment in Japanese patients with type 2 diabetes: Exploring human metabolites associated with visceral fat reduction.

STUDY OBJECTIVE: The effects of the sodium-dependent glucose transporter-2 inhibitor ipragliflozin were compared with metformin in a previous study, which revealed that ipragliflozin reduced visceral fat content by 12%; however, the underlying mechanism was unclear. Therefore, this sub-analysis aimed to compare metabolomic changes associated with ipragliflozin and metformin that may contribute to their biological effects. DESIGN: A sub-analysis of a randomized controlled study. SETTING: Chiba University Hospital and ten hospitals in Japan. PATIENTS: Fifteen patients with type 2 diabetes in the ipragliflozin group and 15 patients with type 2 diabetes in the metformin group with matching characteristics, such as age, sex, baseline A1C, baseline visceral fat area, smoking status, and concomitant medication. INTERVENTIONS: Ipragliflozin 50 mg or metformin 1000 mg daily. MEASUREMENTS: The clinical data were reanalyzed, and metabolomic analysis of serum samples collected before and 24 weeks after drug administration was performed using capillary electrophoresis time-of-flight mass spectrometry. MAIN RESULTS: The reduction in the mean visceral fat area after 24 weeks of treatment was significantly larger (p = 0.002) in the ipragliflozin group (-19.8%) than in the metformin group (-2.5%), as were the subcutaneous fat area and body weight. The A1C and blood glucose levels decreased in both groups. Glutamic pyruvic oxaloacetic transaminase, γ-glutamyl transferase, uric acid, and triglyceride levels decreased in the ipragliflozin group. Low-density lipoprotein cholesterol levels decreased in the metformin group. After ipragliflozin administration, N2-phenylacetylglutamine, inosine, guanosine, and 1-methyladenosine levels increased, whereas galactosamine, glucosamine, 11-aminoundecanoic acid, morpholine, and choline levels decreased. After metformin administration, metformin, hypotaurine, methionine, methyl-2-oxovaleric acid, 3-nitrotyrosine, and cyclohexylamine levels increased, whereas citrulline, octanoic acid, indole-3-acetaldehyde, and hexanoic acid levels decreased. CONCLUSIONS: Metabolites that may affect visceral fat reduction were detected in the ipragliflozin group. Studies are required to further elucidate the underlying mechanisms.

Evaluation of Postnatal Complications in Clinical and Histological Chorioamnionitis in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: Terminating pregnancy appropriately before the intrauterine infection has progressed may have an improved prognosis for preterm infants. We evaluate how the combination of histological chorioamnionitis (hCAM) and clinical chorioamnionitis (cCAM) affects the short-term prognosis of infants. STUDY DESIGN: This retrospective multicenter cohort study based on the Neonatal Research Network of Japan included extremely preterm infants born weighing <1,500 g between 2008 and 2018. Demographic characteristics, morbidity, and mortality were compared between the cCAM(-)hCAM(+) and cCAM(+)hCAM(+) groups. RESULTS: We included 16,304 infants. The progression to cCAM in infants with hCAM was correlated with the increase in home oxygen therapy (HOT) (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.11-1.44) and persistent pulmonary hypertension of the newborn (PPHN) (1.20, 1.04-1.38). Furthermore, increased progression of the hCAM stage in infants with cCAM correlated with an increase in bronchopulmonary dysplasia (BPD; 1.05, 1.01-1.11), HOT (1.10, 1.02-1.18), and PPHN (1.09, 1.01-1.18). However, it had a negative impact on hemodynamically significant patent ductus arteriosus (hsPDA; 0.87, 0.83-0.92) and death before discharge from the neonatal intensive care unit (NICU; 0.88, 0.81-0.96). CONCLUSION: Progression to cCAM in infants with hCAM positively correlated with HOT and PPHN. Progression of hCAM staging in infants with cCAM further increases the prevalence of BPD and the need for HOT and PPHN while reducing the prevalence of hsPDA and death before discharge from the NICU. The effects of the progressive hCAM stage in infants with cCAM vary from positive to negative by disease. KEY POINTS: · Retrospective multicenter cohort study based on the Neonatal Research Network of Japan.. · Clinical and histological chorioamnionitis increases the prevalence of BPD, HOT, and PPHN.. · Progression of histological chorioamnionitis in infants reduces the prevalence of hsPDA and death..

Weight loss improves inflammation by T helper 17 cells in an obese patient with psoriasis at high risk for cardiovascular events.

Psoriasis is a chronic inflammatory skin disease that is associated with obesity and myocardial infarction. Obesity-induced changes in lipid metabolism promote T helper 17 (Th17) cell differentiation, which in turn promotes chronic inflammation. Th17 cells have central roles in many inflammatory diseases, including psoriasis and atherosclerosis; however, whether treatment of obesity attenuates Th17 cells and chronic inflammatory diseases has been unknown. In this study, we found an increase in Th17 cells in a patient with obesity, type 2 diabetes and psoriasis. Furthermore, weight loss with diet and exercise resulted in a decrease in Th17 cells and improvement of psoriasis. This case supports the hypothesis that obesity leads to an increase in Th17 cells and chronic inflammation of the skin and blood vessel walls, thereby promoting psoriasis and atherosclerosis.

Evaluation of newborns with Down syndrome with weight less than 1500 g in the neonatal intensive care unit: A Japanese multicentre study.

AIM: This study aimed to clarify the characteristics and their mortality-related factors in very low birthweight infants with Down syndrome (DS) in Japan. METHODS: This retrospective case-control study enrolled newborns with DS weighing <1500 g admitted to neonatal intensive care unit (NICU) of the perinatal centre registered with the Neonatal Research Network of Japan (NRNJ) database from 2008 to 2019. The clinical characteristics and their mortality-related factors were compared among the Dead group (newborns with DS who died in the NICU), the Survival group (newborns with DS who were alive from the NICU) and the Control group (newborns without congenital or chromosomal condition). RESULTS: A total of 53 656 newborns weighing <1500 g were registered in the NRNJ database for 12 years. Of these, 310 (0.6%) were diagnosed with DS: 62 newborns in the Dead group, 248 in the Survival group and 49 786 in the Control group without chromosomal condition. Logistic analysis revealed that there was a significant difference in the mortality-related factors in congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn; the adjusted odds ratios were 8.6, 121 and 9.5, respectively. Newborns with DS weighing <1000 g showed the earliest death in the NICU on the Kaplan-Meier survival curve (P < 0.01). CONCLUSION: The mortality rate for newborns with DS weighing <1500 g was 20% (5% in the Control group). The mortality-related factors were complications of congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn.

Evaluation of postoperative complications for patent ductus arteriosus in extremely-low-birthweight infants.

BACKGROUND: Patent ductus arteriosus (PDA), which disrupts the hemodynamics early after birth, causes intraventricular hemorrhage and neonatal necrotizing. Unlike medical treatment for hemodynamically significant PDA, there are institutional disparities in the criteria for surgical treatment METHODS: We aimed to clarify the postoperative indications of surgery for hemodynamically significant PDA and the postoperative complications associated with surgery. RESULTS: Thirty-six extremely-low-birthweight infants (median gestational age 25.2 weeks, median birthweight 699 g) required video-assisted thoracoscopic surgery for PDA (VATS-PDA). The treatment indication of VATS-PDA was resistance to medical treatment in 17 cases, relapsed PDA in 15 cases, and no additional administration of indomethacin because of severe side effects in four cases. Complications with VATS-PDA occurred in eight of 36 cases. There were three cases of pneumothorax, two of thoracotomy transition, two of pulmonary hemorrhage, and four of post-ligation cardiac syndrome (PLCS). VATS-PDA-related death occurred in two cases due to PLCS. The frequency of four or more administrations of indomethacin, with or without postoperative complications, was 88% vs. 39%, respectively (P = 0.04). CONCLUSIONS: All postoperative deaths were caused by PLCS, which had the highest risk of poor prognosis. VATS-PDA should be considered for unclosed PDA after one course of indomethacin administration.

Cross-Cultural Nomological Network of Gratitude: Findings From Midlife in the United States (MIDUS) and Japan (MIDJA).

Gratitude enhances prosocial behavior and is considered a positive trait in most cultures, yet relatively little is known about its relationship to other psychological constructs, nor how it varies across diverse cultural contexts. To investigate the cross-cultural consistency of the benefits of having a grateful disposition, the current study examined the nomological network of gratitude in the United States and Japan, using data from two longitudinal studies: Midlife in the United States (MIDUS Refresher Biomarker Project) and Midlife in Japan (MIDJA). Results showed significant positive bivariate associations between trait gratitude and positive psychological functioning (Satisfaction with Life, Sympathy, Anger Control, Cognition Control, and Support/Affectual Solidarity Given to Relational Network) in both the United States and Japan. On the other hand, trait gratitude was negatively correlated with constructs associated with maladaptive psychological processes (Perceived Stress, Social Anxiety, Loneliness, and Anger-In) in both countries. The present findings provide valuable guidance for the development and implementation of future interventions that may lead to positive outcomes in individuals from diverse cultural and ethnic backgrounds.

Optimal timing of video-assisted thoracoscopic surgery for patent ductus arteriosus in preterm infants born at ≤ 28 weeks of gestation.

BACKGROUND: Video-assisted thoracoscopic surgery for patent ductus arteriosus (VATS-PDA) is an alternative surgical procedure to open chest surgery, even in premature infants. This study investigated whether the timing of VATS-PDA has a prognostic impact in premature infants whose operative indication was determined according to the symptomatic PDA and the ineffectiveness of or contraindication to indomethacine therapy. METHODS: We studied 49 infants born at or before 28 weeks of gestation who were admitted to the neonatal intensive care unit between January 2004 and June 2016, and who underwent VATS-PDA. The patients were divided into two groups according to median age at the time of surgery (early group, 24 infants who underwent surgery at ≤ 24 days of life; late group, 25 infants who underwent surgery at ≥ 25 days of life). RESULTS: No significant differences were found in bodyweight at 30 days of age and 40 weeks of corrected gestational age between the groups. The timing of surgery did not affect the operative procedure or postoperative complications. In addition, no differences were observed between the early and late groups in terms of complications associated with prematurity, including intraventricular hemorrhage, incidence and severity of bronchopulmonary dysplasia, and necrotizing enteropathy. CONCLUSION: Video-assisted thoracoscopic surgery for patent ductus arteriosus can be safely performed in premature infants without a preferential timing for the intervention, suggesting that this procedure allows for an elective basis approach after heart failure management with conservative and/or drug therapy in premature infants with PDA.

Vitronectin is Involved in the Morphological Transition of Neurites in Retinoic Acid-Induced Neurogenesis of Neuroblastoma Cell Line Neuro2a.

Vitronectin (Vtn), one of the extracellular matrix proteins, has been reported to result in cell cycle exit, neurite formation, and polarization of neural progenitor cells during neurogenesis. The underlying mechanism, however, has not been fully understood. In this study, we investigated the roles of Vtn and its integrin receptors, during the transition of neurites from multipolar to bipolar morphology, accompanying the cell cycle exit in neural progenitor cells. We used mouse neuroblastoma cell line Neuro2a as a model of neural progenitor cells which can induce cell cycle exit and the morphological transition of neurites by retinoic acid (RA)-stimulation. Treatment with an antibody for Vtn suppressed the RA-induced cell cycle exit and multipolar-to-bipolar transition. Furthermore, immunostaining results showed that in the cells displaying multipolar morphology Vtn was partially localized at the tips of neurites and in cells displaying bipolar morphology at both tips. This Vtn localization and multipolar-to-bipolar transition was perturbed by the transfection of a dominant negative mutant of cell polarity regulator Par6. In addition, a knockdown of ß5 integrin, which is a receptor candidate for Vtn, affected the multipolar-to-bipolar transition. Taken together, these results suggest that Vtn regulates the multipolar-to-bipolar morphological transition via αvß5 integrin.

Self-Compassion and Cultural Values: A Cross-Cultural Study of Self-Compassion Using a Multitrait-Multimethod (MTMM) Analytical Procedure.

Self-compassion is natural, trainable and multi-faceted human capacity. To date there has been little research into the role of culture in influencing the conceptual structure of the underlying construct, the relative importance of different facets of self-compassion, nor its relationships to cultural values. This study employed a cross-cultural design, with 4,124 participants from 11 purposively sampled datasets drawn from different countries. We aimed to assess the relevance of positive and negative items when building the self-compassion construct, the convergence among the self-compassion components, and the possible influence of cultural values. Each dataset comprised undergraduate students who completed the "Self-Compassion Scale" (SCS). We used a confirmatory factor analysis (CFA) approach to the multitrait-multimethod (MTMM) model, separating the variability into self-compassion components (self-kindness, common humanity, mindfulness), method (positive and negative valence), and error (uniqueness). The normative scores of the Values Survey Module (VSM) in each country, according to the cultural dimensions of individualism, masculinity, power distance, long-term orientation, uncertainty avoidance, and indulgence, were considered. We used Spearman coefficients (r s) to assess the degree of association between the cultural values and the variance coming from the positive and negative items to explain self-compassion traits, as well as the variance shared among the self-compassion traits, after removing the method effects produced by the item valence. The CFA applied to the MTMM model provided acceptable fit in all the samples. Positive items made a greater contribution to capturing the traits comprising self-compassion when the long-term orientation cultural value was higher (r s = 0.62; p = 0.042). Negative items did not make significant contributions to building the construct when the individualism cultural value was higher, but moderate effects were found (r s = 0.40; p = 0.228). The level of common variance among the self-compassion trait factors was inversely related to the indulgence cultural value (r s = -0.65; p = 0.030). The extent to which the positive and negative items contribute to explain self-compassion, and that different self-compassion facets might be regarded as reflecting a broader construct, might differ across cultural backgrounds.

Self-Construals, Anger Regulation, and Life Satisfaction in the United States and Japan.

Previous studies have reported evidence that indicates differences between Western and East Asian cultures in anger regulation and its psychological consequences. However, many of these studies have focused on a specific anger regulation strategy and its relation with a psychological consequence. Here, we developed an integrated model that can comprehensively examine three different anger regulation strategies (anger suppression, expression, and control), independent and interdependent self-construals as the psychological antecedent, and life satisfaction as the psychological consequence. We estimated the model using large samples of American and Japanese adults to examine the associations between the two self-construals, three anger regulation strategies, and life satisfaction. We compared the difference in the patterns of relationships among the key constructs between the American and Japanese samples. The results confirmed previously suggested cultural differences while also discovering new culturally different paths. The results generally suggest that individual-level self-construals matter more when anger is a culturally condoned emotion (vs. condemned). The implications and limitations of the integrated model are discussed.

Relationship between bicultural identity and psychological well-being among American and Japanese older adults.

In a large national sample of American and Japanese older adults, this study investigated how bicultural identity affects perception of health and well-being in 11 individual psychological variables (i.e. positive well-being: self-esteem, optimism, subjective well-being Japanese equivalent, gratitude, Positive and Negative Affect Schedule-positive adjectives, and satisfaction with life; negative well-being: depression, pessimism, social anxiety, Positive and Negative Affect Schedule-negative adjectives, and perceived stress). This sample consisted of 1248 Americans from the Midlife in the United States survey, 2004-2006, and 380 Japanese from the Midlife in Japan survey in Tokyo, Japan, 2008-2010. Results showed that bicultural individuals (having both highly independent and interdependent self-construals) in both countries tend to exhibit higher scores across most perceived health and well-being measures when compared to other groups (i.e. marginal, interdependent, and independent). Cultural-specific aspects of self-construal, health, and well-being are explained to support the findings. Discussion of these findings and their implications is also provided.

Effects of anger regulation and social anxiety on perceived stress.

The mediating role of social anxiety was explored within the effect of anger regulation on perceived stress in the national sample of American and Japanese older adults. Results indicated that anger suppression is a significant factor in perceived stress mediated by social anxiety. Anger suppression was also directly related to perceived stress. The correlation of anger suppression with social anxiety was stronger in Japan than in the United States. Understanding both universal and culture-specific aspects of emotion regulation and perceived stress will be essential for the development of sound theory, future research, and effective prevention and intervention efforts.

Effects of self-construal and its relationship with subjective well-being across cultures.

The purpose of this study is to test cross-cultural predictions of the associations between goal pursuits and subjective well-being among 601 college students (200 in Japan and 401 in the United States). The results indicated that interdependence in all cultures was associated with socially oriented subjective well-being. In the United States, it was also correlated with social goal pursuit. However, independence in the United States correlated with individual-oriented subjective well-being, while in Hawaii, it also correlated with hedonic goal pursuit. Discussion of these results and their implications are provided.

Effects of social capital on general health status.

This paper discusses the concept of social capital as a potential factor in understanding the controversial relationship between income inequality and individual health status, arguing a positive, important role for social capital. Most of the health research literature focuses on individual health status and reveals that social capital increases individual health. However, the difficulty in measuring social capital, together with what may be the nearly impossible task of attributing causality, should relegate the concept to a more theoretical role in health research. Nonetheless, social capital receives academic attention as a potentially important factor in health research. This paper finds that the mixed results of empirical research on income inequality and health status remain a problem in the context of defining a stable relationship between socioeconomic status and health status. Clearly, further research is needed to elaborate on the income inequality and health relationship. In addition, focused, rigorous examination of social capital in a health context is needed before health researchers can comfortably introduce it as a concept of influence or significance.

Induction of aldo-keto reductases (AKR1C1 and AKR1C3) abolishes the efficacy of daunorubicin chemotherapy for leukemic U937 cells.

Continuous exposure to daunorubicin (DNR) confers resistance against the drug-elicited lethality of leukemic cells and then reduces the remission rate. However, the detailed mechanisms involved in resistance development of leukemic cells to DNR remain unclear. Upregulation of aldo-keto reductases (AKRs) in human leukemic U937 cells was evaluated by gene-specific PCR and western blot analyses, and the contribution of AKRs toward the DNR sensitivity was assessed using gene expression and RNA-interference techniques and specific inhibitors. In addition, DNR reduction and cell differentiation were analyzed by fluorescence high-performance liquid chromatography and flow cytometry, respectively. Treatment with high doses of DNR triggered apoptotic induction of U937 cells through the production of reactive oxygen species (ROS) and a ROS-dependent mechanism. In contrast, DNR, at its sublethal doses, induced the expression of AKR1C1 and AKR1C3, both of which reduced the DNR sensitivity of the cells. The enzymes did not interfere with the cell differentiation caused by DNR, whereas their upregulation facilitated reduction of the anticancer drug and a ROS-derived lipid aldehyde 4-hydroxy-2-nonenal. These results suggest crucial roles of AKR1C1 and AKR1C3 in the acquisition of DNR resistance of leukemic cells by metabolizing both DNR and cytotoxic aldehydes derived from ROS-linked lipid peroxidation.

Influences of social capital on health and well-being from qualitative approach.

The social capital surrounding health including health and well-being, the way in which they function as multi-dimensional constructs, and the potential stability of relationships among the social capital were examined across universities in Hawaii and Japan. Maintaining or strengthening social factors of collective and individual health and well-being is a core factor of social capital and is instrumental in reducing worry and increasing trust. Qualitative in-depth interviews with 64 male and female college students (32 college students at the University of Hawaii at Manoa; 32 college students at Reitaku University in Japan) were used to collect information on social capital of health and well-being and associated concepts; students' perceptions were grouped under 11 themes. The data indicates that social capital has an impact on college students' health and well-being. They also suggest that differences in health status and well-being can be plausibly attributed to processes associated with socio-environmental circumstances and situations.