Synergistic effect of metformin and vitamin D3 on osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells under high d-glucose conditions.

Introduction: Vitamin D3 plays a vital role in bone health, with low levels of vitamin D3 being related to skeletal fragility, fractures, and metabolic disorders such as diabetes. Metformin is known as an antihyperglycemic agent for regulating blood sugar. A correlation between diabetes mellitus and osteoporosis is attracting considerable interest, and research to find the prevention and treatment is gradually being studied. In this study, we investigated the effect of metformin and vitamin D3 on osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (AT-MSCs) under high d-glucose concentrations and optimized by combining vitamin D3 and metformin in the process. Methods: ROS production of AT-MSCs under high d-glucose conditions was measured by DCFH-DA assay. The differentiated AT-MSCs were analyzed by Alizarin Red S staining and optical density measurement. The investigation involved the examination of osteogenic master genes' expressions using quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques. Results: Interestingly, the results have shown that human AT-MSCs will exhibit high ROS accumulation and low osteogenic differentiation capabilities, indicated by low calcium deposition, as well as low expression of indicative genes such as ALP, Runx-2 under high d-glucose conditions. The combination of vitamin D3 and metformin remarkedly accelerated the osteogenic differentiation of AT-MSCs under high d-glucose concentrations more effectively than the administration of either agent. Conclusions: This study partially explains an aspect of an in vitro model for pre-clinical drug screening for osteoporosis-related diabetic pathological mechanisms, which can be applied for further research on the prevention or treatment of osteoporosis in diabetic patients.

Gender disparities among publications within international sexual medicine urology journals and the impact of blinding in the review process.

BACKGROUND: While female urologists are known to publish at less frequency than their male peers, The Journal of Sexual Medicine was reported to have among the highest growth in female authorship from 2002 to 2020 in urology journals. AIM: We sought to assess the frequency of female authorship in sexual medicine journals worldwide and the factors that affect this, including the blinded/unblinded review process. METHODS: Eleven sexual medicine journals were assessed for geographic location, peer review method, and SCImago Journal Rank citation index (a metric of citation frequency and prestige). Journals were grouped into top, middle, and bottom quartiles based on metric score. Web of Science was used to access the publications' first, second, last, and corresponding authors from the past 5 years. An internet search or Gender-API.com was used to determine the gender identities of authors. Univariate and multivariable logistic regression models were performed. OUTCOMES: Outcomes included the likelihood of female authorship (first, second, last, and corresponding) based on journal location and ranking, the clustering of female authors, the journal's peer review process, and the frequency of female editorial board members. RESULTS: Overall, 8938 publications were identified. Women represented 30.7%, 31.3%, 21.3%, and 18.7% of the first, second, last, and corresponding authors, respectively; gender was unable to be assessed for 2.6%, 17.2%, 7.3%, and 2.7%. On univariate analysis, journals from North America, in the top quartile, and with a double-blind review process were more likely to have female authors (P < .001). On multivariate analysis, articles were more likely to have a female first author if they had a double-blind peer review process (odds ratio [OR], 1.20; 95% CI, 1.02-1.40), a female second author (OR, 2.54; 95% CI, 2.26-2.85), or a female corresponding author (OR, 7.80; 95% CI, 6.69-9.10). CLINICAL IMPLICATIONS: Gender-concordant mentoring and universal double-blind manuscript review processes may minimize the impact of gender bias and increase female authorship rates, in turn producing more diverse research. STRENGTHS AND LIMITATIONS: This is the first study assessing female authorship in sexual medicine journals. Limitations include not assessing every author listed on articles and being unable to determine gender identities for some authors. CONCLUSION: Female authorship rates are higher than reported rates of practicing female urologists but still lower than their male peers. Female authors were more likely to be published in journals with double-blind peer review processes and when publishing with additional female authors.

Structural Equation Model for Social Support and Quality of Life Among Individuals With Mental Health Disorders During the COVID-19 Pandemic.

BACKGROUND: In light of the COVID-19 pandemic, the distribution of social support for mental health problems has likely become unequal. Family- and community-based social support has been recognized as a promising approach for mental disorders; however, limited global frameworks have been applied to developing countries such as Vietnam. OBJECTIVE: The aim of this study was to evaluate the quality of life and social support among patients with mental health disorders in Vietnam and to investigate the factors associated with quality of life among these patients. METHODS: A cross-sectional study was conducted on 222 psychiatric patients in Hanoi from 2020 to 2022. A structured questionnaire was developed based on four standardized scales: Mental Well-Being-5 scale, Multidimensional Scale of Perceived Social Support, EuroQoL-visual analog scale (EQ-VAS), and EuroQoL-5 dimensions-5 levels (EQ-5D-5L) scale. Tobit regression was used to identify factors associated with the EQ-5D-5L and EQ-VAS scores. Structural equation modeling was applied to verify the relationship between quality of life and social support. RESULTS: The results showed that perceived support from family scored the highest compared to support from friends and significant others. Patients with depression reported the lowest quality of life and perceived social support. Structural equation modeling showed a root mean square error of approximation of 0.055 (90% CI 0.006-0.090), comparative fit index of 0.954, Tucker-Lewis index of 0.892, and standardized root mean squared error of 0.036 (P<.001). The hypothetical model indicated statistically significant correlations between EQ-VAS score and social support (P=.004), EQ-5D-5L and mental well-being (P<.001), and social support and mental well-being (P<.001). Critical deterioration of quality of life and inconsistency in social support for patients with mental illness were also recorded. CONCLUSIONS: There is a need to enhance social support and service delivery in Vietnam, focusing on occupation and quality of life. The correlations between social support, quality of life, and mental health issues suggest the potential of a clinical-social integrated intervention model of care.

Content, face, and construct validity of the Irritable Bowel Syndrome Quality of Life (IBS-QOL) as a measure of bowel-related quality of life in spinal cord injury.

INTRODUCTION: Neurogenic bowel dysfunction is commonly encountered after a spinal cord injury (SCI), leading to a tremendous impact on quality of life (QOL). The neurogenic bowel dysfunction score (NBDS) is commonly used to measure the severity of bowel dysfunction and predict QOL. However, there is no comprehensive instrument to assess bowel-specific QOL for SCI patients. Instead, the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) questionnaire evaluates the impact of bowel dysfunction on several aspects of QOL, although this questionnaire has not been validated for the SCI population. Motivated by the compelling need of instruments to accurately evaluate the QOL in patients who develope NBD after SCI, we aimed to assess the construct, content, and face validity of IBS-QOL in this population. METHODS: Adult SCI patients with at least 3 months after their injury were recruited from the outpatient clinic of a national rehabilitation hospital. Patients completed the NBDS and IBS-QOL via telephone interview or paper survey in the clinic. Content and face validity were assessed via interviews with professionals with expertise in providing chronic care for SCI, as well as a subgroup of patients. Construct validity was assessed using the hypotheses testing method. Internal consistency was assessed using Cronbach's ⍺. Factor analysis was performed to assess the dimensionality of the IBS-QOL in the SCI population. RESULTS: A total of 106 patients with a median age of 45.5 years (interquartile range: 21-79) participated in the study. The majority of the sample were men (n = 82, 77%) and had endured thoracolumbar injuries (n = 74, 71.2%). Twelve patients (seven English- and five Spanish speakers) and six professionals took part in content/face validation interviews. The median IBS-QOL total score was 15.91/100 (interquartile range: 4.55-33.14). IBS-QOL differentiated the subgroups of patients with severe bowel symptoms in terms of uneasiness, sweating, or headaches during bowel emptying (p = 0.0003), time spent on bowel emptying (p = 0.0065), flatus incontinence (p = 0.0076), and overall satisfaction with bowel function (p < 0.001), demonstrating its adequate construct validity. Interviews with the patients and professionals supported the comprehensiveness, comprehensibility, and relevance of IBS-QOL for assessment of bowel-related QOL in the SCI population. Item-level analysis of professional responses showed that 97% of questions were relevant to the construct and population of interest. Internal consistency analysis yielded a Cronbach's ⍺ of 0.9684. Exploratory factor analysis yielded six underlying factors which cumulatively accounted for 72.21% of the total variance, reflecting the dimensionality of bowel-related QOL in SCI population. DISCUSSION: IBS-QOL questionnaire is a comprehensive measure of bowel-related QOL which encompasses the concerns of SCI patients. Our findings support the content, face and construct validity of IBS-QOL as a measure of bowel-related QOL in SCI. Further studies are warranted to assess the reliability and responsiveness of IBS-QOL, and to evaluate its performance across different patient populations.

Health Care Economic Burden of Treatment and Rehabilitation for Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

PURPOSE: The clinical, social, and economic impacts of neurogenic lower urinary tract dysfunction (NLUTD) on individuals and health care systems are thought to be immense, yet the true costs of care are unknown. The aims of this study are to illuminate the global costs related to the current state of care for NLUTD. MATERIALS AND METHODS: A systematic review of the literature was performed using MEDLINE, the National Health Service Economic Evaluation Database, and the Cochrane Specialized Urology and Incontinence Registers. Studies reporting the health care costs of NLUTD were identified. All steps of the review were performed by 2 independent reviewers. Costs were converted to 2022 U.S. dollars and reported for different categories of services. RESULTS: A total of 13 studies were included in the final review (12 from high-income economy, and 1 from an upper-middle-income economy). Routine maintenance care varied notably across studies in terms of included services. Annual supportive costs ranged from $2,039.69 to $12,219.07 with 1 study estimating lifetime costs of $112,774 when complications were considered. There were limited data on the costs of care from the patient's perspective. However, catheters and absorbent aids were estimated to be among the costliest categories of expenditure during routine care. More invasive and reconstructive treatments were associated with significant costs, ranging between $18,057 and $55,873. CONCLUSIONS: NLUTD incurs a variety of health care expenditures ranging from incontinence supplies to hospitalizations for management of complications and leads to a significant burden for health care systems over the patient's lifetime. Approaches to NLUTD that focus on functional rehabilitation and restoration, rather than on management of complications, may prove to be a less costly and more effective alternative.

Receptor subtype discrimination using extensive shape complementary designed interfaces.

To discriminate between closely related members of a protein family that differ at a limited number of spatially distant positions is a challenge for drug discovery. We describe a combined computational design and experimental selection approach for generating binders targeting functional sites with large, shape complementary interfaces to read out subtle sequence differences for subtype-specific antagonism. Repeat proteins are computationally docked against a functionally relevant region of the target protein surface that varies in the different subtypes, and the interface sequences are optimized for affinity and specificity first computationally and then experimentally. We used this approach to generate a series of human Frizzled (Fz) subtype-selective antagonists with extensive shape complementary interaction surfaces considerably larger than those of repeat proteins selected from random libraries. In vivo administration revealed that Wnt-dependent pericentral liver gene expression involves multiple Fz subtypes, while maintenance of the intestinal crypt stem cell compartment involves only a limited subset.