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Yvonne Commodore-Mensah,1,2,* Sabianca Delva,3,* Oluwabunmi Ogungbe,1,2,* Lauren A Smulcer,4 Sally Rives,1 Cheryl R Dennison Himmelfarb,1,5,6 Miyong T Kim,7 Lee Bone,1,2,5 David Levine,1,2,5 Martha N Hill1,2,5 1Johns Hopkins School of Nursing, Baltimore, MD, USA; 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3William F. Connell School of Nursing, Boston College, Chestnut Hill, MA, USA; 4Elara Caring, Fort Polk North, LA, USA; 5Department of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; 6Department of Health, Behavior and Society, Johns Hopkins Bloombery School of Public Health, Baltimore, MD, USA; 7School of Nursing, University of Texas at Austin, Austin, TX, USA*These authors contributed equally to this workCorrespondence: Yvonne Commodore-Mensah, Johns Hopkins School of Nursing, 525 N. Wolfe Street, Room N530U, Baltimore, MD, 21205, USA, Tel +1 4106141519, Email ycommod1@jhmi.eduBackground: Poor medication adherence hampers hypertension control and increases the risk of adverse health outcomes. Medication adherence can be measured with direct and indirect methods. The Hill-Bone Compliance to High Blood Pressure Therapy (HBCHBPT) Scale, one of the most popular adherence measures, indirectly assesses adherence to hypertension therapy in three behavioral domains: appointment keeping, diet and medication adherence.Aim: To synthesize evidence on the use of the HBCHBPT Scale, including psychometric properties, utility in diverse patient populations, and directions for future clinical use and research.Methods: We searched electronic databases, specifically CINAHL, PubMed, PsychInfo, Embase, and Web of Science. We included original studies that used the HBCHBPT Scale or its subscales to measure a health outcome, or methodological studies involving translations and validations of the scale. We extracted and synthesized data following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.Results: Fifty studies were included in this review, 44 on hypertension, two on diabetes, and others on other chronic conditions. The scale was successfully translated into numerous languages and used in descriptive and intervention studies. The scale demonstrated sound psychometric properties (Cronbach’s α coefficient 0.75) and sensitivity to capture intervention effects when used to evaluate the effectiveness of high blood pressure adherence interventions. The medication-taking subscale of HBCHBPT performs best and is widely used in diverse contexts to assess medication adherence for chronic conditions.Conclusion: The HBCHBPT Scale has high versatility globally and has been used in various settings by various healthcare worker cadres and researchers. The scale has several strengths, including high adherence phenotyping capabilities, contributing to the paradigm shift toward personalized health care.Keywords: medication adherence, treatment adherence, treatment compliance, hypertension, high blood pressure, Hill Bone Medication Adherence Scale, Hill-Bone Compliance to Blood Pressure Therapy Scale

Objectives: Language accommodation is indispensable in making evidence-based interventions available and accessible to ethnic minorities with limited English proficiency. As part of the larger effort to culturally adapt the Savvy Caregiver Program for Korean American dementia caregivers, we first conducted linguistic adaptation, and the present study reports the preliminary findings on participants' changes in depressive Symptoms., Methods: The linguistically adapted program was delivered to two small groups of Korean American dementia caregivers (total n  = 13) by two Savvy-certified Korean-speaking trainers. Participants' depressive symptoms were assessed at three time points (pre-intervention, immediate post-intervention, and 6-month follow-up)., Results: Following the intervention, participants exhibited lowered depressive symptoms ( t  = 8.64, p  < .001, Cohen's d  = .89). This benefit was sustained at 6-month follow-up., Conclusions: Findings suggest that the therapeutic benefit of the Savvy Caregiver Program could potentially be shared with linguistic minorities when delivered in their native language., Clinical Implications: Although limited in its scope and nature, the pilot study with linguistic adaptation sheds light on efforts to close the gap in the evidence-based intervention delivery.

Using data from Korean-American residents ( N = 343) in subsidized senior housing in the Los Angeles area, we examined the effect of peer bullying on mental health. About 18% of the sample had been a target of bullying, and over 31% had witnessed someone being bullied. Being a target of bullying was a significant predictor for both depressive symptoms and anxiety, whereas witnessing other residents being bullied was a significant predictor for anxiety only. Findings shed light on the adverse mental health impacts of peer bullying among ethnic minority older residents in senior housing.

G-protein-coupled receptors are a diverse class of cell surface receptors that orchestrate numerous physiological functions. The G-protein-coupled receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which are metabolites of dietary fermentation by the host's intestinal bacteria. These receptors have gained attention as potential therapeutic targets against various diseases because of their SCFA-mediated beneficial effects on the host's intestinal health. Mounting evidence has associated the activity of these receptors with chronic metabolic diseases, including obesity, diabetes, inflammation, and cardiovascular disease. However, despite intensive research using various strategies, including gene knockout (KO) mouse models, evidence about the precise roles of GPR41 and GPR43 in disease treatment remains inconsistent. Here, we comprehensively review the latest findings from functional studies of the signaling mechanisms that underlie the activities of GPR41 and GPR43, as well as highlight their multifaceted roles in health and disease. We anticipate that this knowledge will guide future research priorities and the development of effective therapeutic interventions., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: We examined how the association between cognitive performance and cognitive health appraisal would be moderated by vision and/or hearing impairment., Methods: Data were collected from 315 older Korean-American residents in subsidized senior housing in Los Angeles ( M age = 79.4 years). Linear regression models examined the direct and interactive effects of cognitive performance, vision impairment, and hearing impairment on cognitive health appraisal., Results: Negative appraisal of cognitive health was associated with lower cognitive performance and poorer ratings for vision and hearing. Moreover, we found a significant interaction between cognitive performance and hearing impairment ( β = .13, p < .05), as well as a three-way interaction among cognitive performance, vision impairment, and hearing impairment ( β = .12, p < .05)., Discussion: The association between objective and subjective measures of cognition was weakened when hearing was impaired. Such a pattern was further evident when both vision and hearing were impaired., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In California, preventive dental care is covered by Medi-Cal (California's Medicaid program). However, many beneficiaries do not use their dental benefits. Given that a lack of knowledge about oral health and insurance coverage contributes to this underutilization, promoting the use of dental benefits among eligible individuals via an educational program is imperative. Responding to the particular needs of older immigrants with limited English proficiency, we developed a digital oral health intervention for older Korean-American Medi-Cal enrollees in Los Angeles. This educational intervention is designed to be delivered via computers and the Internet. It consists of a 15-min self-running PowerPoint presentation narrated in Korean with links to additional information on the Internet. The slides contain information about the basic etiology of oral diseases, oral hygiene, common myths about oral health and dental care, Medi-Cal coverage of preventive dental care, and how to find a dental clinic., Methods: We pilot tested the intervention with 12 participants to examine its feasibility and acceptability. We also obtained participants' qualitative feedback about the intervention., Results: A post-intervention quantitative assessment yielded high participant satisfaction and improved oral health and dental care knowledge. Participant responses to the intervention yielded four themes: (1) content and structure, (2) linguistic and cultural aspects, (3) delivery mode, and (4) additional concerns and suggestions., Conclusions: Our findings confirm the intervention's feasibility and acceptability and suggest further refinement., (© 2024. The Author(s).)

Background: Hydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B 12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration., Methods: A total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally ( n  = 15), (ii) slow drip saline intratracheally ( n  = 15), (iii) fast drip saline intratracheally ( n  = 15), and (iv) slow drip cobinamide intratracheally ( n  = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy., Results: The mean (± standard deviation) weight for all animals ( n  = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups ( P  < 0.05). The slow and no saline control groups were not significantly different ( P  = 0.59). The slow cobinamide group did significantly better than the slow saline group ( P  = 0.021)., Discussion: The ability to use intratracheal cobinamide as an antidote to hydrogen sulfide poisoning is a novel approach to mass-casualty care. The major limitations of this study are that it was conducted in a single species at a single inhaled hydrogen sulfide concentration. Repeated investigations in other species and at varying levels of hydrogen sulfide exposure will be needed before any definitive recommendations can be made., Conclusions: We demonstrated that intratracheal cobinamide and fast saline drip improved survival for hydrogen sulfide gas inhalation in rabbit models. Although further study is required, our results suggest that intratracheal administration of cobinamide and fast saline may be useful in hydrogen sulfide mass-casualty events.

Background: The aim of this study was to assess the efficacy of the Model for End-Stage Liver Disease (MELD) score in predicting postoperative complications following total shoulder arthroplasty (TSA)., Methods: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent TSA between 2015 and 2019. The study population was subsequently classified into two categories: those with a MELD score ≥ 10 and those with a MELD score < 10. A total of 5265 patients undergoing TSA between 2015 and 2019 were included in this study. Among these, 4690 (89.1%) patients had a MELD score ≥ 10, while 575 (10.9%) patients had a MELD score < 10. Postoperative complications within 30 days of the TSA were collected. Multivariate logistic regression analysis was conducted to explore the correlation between a MELD score ≥ 10 and postoperative complications. The anchor based optimal cutoff was calculated by receiver operating characteristic analysis to determine the MELD score cutoff that most accurately predicts a specific complication. Youden's index (J) determined the optimal cutoff point calculation for the maximum sensitivity and specificity; these were deemed to be "acceptable" if the area under curve (AUC) was greater than 0.7 and "excellent" if greater than 0.8., Results: Multivariate regression analysis found a MELD score ≥ 10 to be independently associated with higher rates of reoperation (OR, 2.08; P  = .013), cardiac complications (OR, 3.37; P  = .030), renal complications (OR, 7.72; P  = .020), bleeding transfusions (OR, 3.23; P  < .001), and nonhome discharge (OR, 1.75; P  < .001). The receiver operating characteristic analysis showed that AUC for a MELD score cutoff of 7.61 as a predictor of renal complications was 0.87 (excellent) with sensitivity of 100.0% and specificity of 70.0%. AUC for a MELD score cutoff of 7.76 as a predictor of mortality was 0.76 (acceptable) with sensitivity of 81.8% and specificity of 71.0%., Conclusion: A MELD score ≥ 10 was correlated with high rates of reoperation, cardiac complications, renal complications, bleeding transfusions, and nonhome discharge following TSA. MELD score cutoffs of 7.61 and 7.76 were effective in predicting renal complications and mortality, respectively., (© 2024 The Authors.)

Background: The Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) is a tool that systematically guides decision-making and reporting of adaptations made to evidence-based interventions. Using FRAME, we documented the process and outcomes of adapting the Savvy Caregiver Program (SCP) for Korean American dementia caregivers., Methods: Sequential adaptation was initiated with linguistic attunement, followed by pilot implementation and full adaptation. Our data-driven adaptation with multiple data sources and a feedback loop among multiple stakeholders yielded a total of 32 modifications, and each was coded according to the eight domains of FRAME: (1) what was modified, (2) who participated in recommending and deciding the modification to be made, (3) when the modification occurred, (4) whether the modification was planned, (5) whether the modification was fidelity-consistent, (6) whether the modification was temporary, (7) at what level of delivery, the modification was made, and (8) why the modification was made., Results: The areas of adaptation were evenly distributed across context (37.5%), content (31.2%), and training (31.2%). The primary reasons for modification were for engagement (62.5%), followed by fit with recipients (43.8%) and outcome improvement (31.1%). About 66% of the modifications were applied to the entire target group, and all modifications were fidelity-consistent., Conclusions: The FRAME categorization provided a detailed understanding of the process and nature of adapting the SCP and served as a foundation for further implementation and scale-up. FRAME not only serves as a guide for adapting evidence-based interventions but also promotes their replicability and scalability., (© 2024. The Author(s).)

Subsidized senior housing helps many socioeconomically disadvantaged older adults pursue independent living and aging in place. However, cognitive impairment or dementia poses a critical challenge to many residents' ability to live independently and safely. Focusing on Korean American dementia caregivers, a group known to be vulnerable to caregiving burden but understudied, we explored the safety of persons with dementia in senior housing from the perspectives of caregivers. Qualitative data from nine caregivers whose care recipients were current or former residents of subsidized senior housing in Los Angeles were analyzed by the constant comparative method. Major concerns emerged were: (1) fire risks, (2) wandering, (3) physical injury (e.g., self-harm, falls), and (4) potential neglect. Caregivers also mentioned errors in the self-administration of medications, potential financial exploitation, and interpersonal conflicts. These concerns provide implications for services and programs for the safety of persons with dementia who live in senior housing.

Considering that individuals' health information can enable their adoption of health behaviors, we examined the use of health information sources related to COVID-19 and its association with preventive behaviors in a sample of older residents in Seoul, South Korea (N = 400, M age = 76.1 years). Latent profile analysis of 12 sources of health information representing conventional media, online sources, interpersonal networks, and health professionals or authorities yielded a 4-group typology: limited, moderate/traditional, moderate/digital, and diverse. In a multivariate model with the diverse group as a reference, the limited group (B = -4.48, SE = 1.14, p < .001) and the moderate/digital group (B = -2.73, SE = 0.76, p < .001) were associated with lower adherence to COVID-19 preventive behaviors. Our findings support the heterogeneity in the use of health information sources and the hypothesis that groups with restricted sources of health information would report less desirable behaviors. The findings also underscored the importance of proper use of digital health information. Efforts should be made not only to help older adults with low education access diverse sources of health information, including digital sources, but also to empower them to build digital and health literacy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To calculate and determine what factors are associated with achieving the Minimal Clinically Important Difference (MCID) and the Substantial Clinical Benefit (SCB) of Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity Computer Adaptive Testing v2.0 (UE), Pain Interference (P-Interference), and Pain Intensity (P-Intensity) in patients undergoing arthroscopic rotator cuff repair (aRCR)., Methods: The change in PROMIS scores representing the optimal cutoff for a ROC curve with an area under the curve analysis was used to calculate the anchor-based MCID and SCB. To assess the responsiveness of each PROM, effect sizes and standardized response means (SRM) were calculated. To identify factors associated with attaining the MCID and SCB, univariate and multivariate logistic regression analyses were performed., Results: A total of 323 patients with an average age of 59.9 ± 9.5 were enrolled in this study, of which, 187/323 [57.9%] were male and 136/323 [42.1%] were female. The anchor-based MCID for PROMIS UE, P-Interference, and P-Intensity was: 9.0, 7.5, and 11.2, respectively. The respective SCB was 10.9, 9.3, and 12.7. Effect size and SRM were: PROMIS UE (1.4, 1.3), P-Interference (1.8, 1.5), and P-Intensity (2.3, 2.0). Lower preoperative P-Intensity scores (p = 0.02), dominant arm involvement (p = 0.03), and concomitant biceps tenodesis (p = 0.03) were associated with patients achieving the SCB for PROMIS UE., Conclusion: A large responsiveness for each of the PROMIS instruments due to the majority of patients reporting great improvement after aRCR and a small standard deviation across all outcome measures was shown in our study. Lower preoperative P-Intensity scores and concomitant biceps tenodesis were associated with higher odds of achieving the SCB for PROMIS UE. The knowledge of MCID and SCB values for PROMIS instruments will allow the surgeon to determine whether the improvements in the PROMIS scores after aRCR are clinically meaningful., Level of Evidence: Level III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

In South Korea, rapid economic growth and modernization have led to changes in lifestyle factors that may affect age at natural menopause. Data from 4,793 women aged ≥55 years, who had a natural menopause, were analyzed from the Korea National Health and Nutrition Examination Survey (2013-2017). Multinomial logistic regression was used to examine the association between lifestyle factors and age at natural menopause after adjusting for birth cohort (Model 1) and sociodemographic and reproductive factors (Model 2). Overall, 3.1% of women experienced premature menopause (<40 years), 7.6% early menopause (40-44 years), and 12.8% late menopause (≥55 years). Women born in the 1940s or earlier among the birth cohorts had the highest prevalence of premature (70.0%), early (58.5%), and late (43.1%) menopause. In Model 2, current smoking (odds ratio = 3.99 and 95% confidence interval = 1.35-11.81) was associated with premature menopause. Low (<18.5 kg/m 2 ) and high (≥25 kg/m 2 ) body mass index were associated with early (odds ratio = 2.30 and 95% confidence interval = 1.01-5.22) and late (odds ratio = 1.38 and 95% confidence interval = 1.10-1.72) menopause respectively. Conversely, there was no association between age at natural menopause and alcohol consumption. The results suggest that healthy lifestyle factors, such as not smoking and proper weight maintenance, are significant factors affecting age at natural menopause. Our findings may help develop health policies and provide targeted care to improve women's health after midlife.

Background: Heart failure (HF) is the leading cause of hospitalization among older adults in the United States. There are substantial racial and geographic disparities in HF outcomes, with patients living in southern US states having a mortality rate 69% higher than the national average. Self-management behaviors, particularly daily weight monitoring and physical activity, are extremely important in improving HF outcomes; however, patients typically have particularly low adherence to these behaviors. With the rise of digital technologies to improve health outcomes and motivate health behaviors, sensor-controlled digital games (SCDGs) have become a promising approach. SCDGs, which leverage sensor-connected technologies, offer the benefits of being portable and scalable and allowing for continuous observation and motivation of health behaviors in their real-world contexts. They are also becoming increasingly popular among older adults and offer an immersive and accessible way to measure self-management behaviors and improve adherence. No SCDGs have been designed for older adults or evaluated to test their outcomes., Objective: This randomized clinical trial aims to assess the efficacy of a SCDG in integrating the behavioral data of participants with HF from weight scale and activity tracker sensors to activate game progress, rewards, and feedback and, ultimately, to improve adherence to important self-management behaviors., Methods: A total of 200 participants with HF, aged ≥45 years, will be recruited and randomized into 2 groups: the SCDG playing group (intervention group) and sensor-only group (control group). Both groups will receive a weight scale, physical activity tracker, and accompanying app, whereas only the intervention group will play the SCDG. This design, thereby, assesses the contributions of the game. All participants will complete a baseline survey as well as posttests at 6 and 12 weeks to assess the immediate effect of the intervention. They will also complete a third posttest at 24 weeks to assess the maintenance of behavioral changes. Efficacy and benefits will be assessed by measuring improvements in HF-related proximal outcomes (self-management behaviors of daily weight monitoring and physical activity) and distal outcomes (HF hospitalization, quality of life, and functional status) between baseline and weeks 6, 12, and 24. The primary outcome measured will be days with weight monitoring, for which this design provides at least 80% power to detect differences between the 2 groups., Results: Recruitment began in the fall of 2022, and the first patient was enrolled in the study on November 7, 2022. Recruitment of the last participant is expected in quarter 1 of 2025. Publication of complete results and data from this study is expected in 2026., Conclusions: This project will generate insight and guidance for scalable and easy-to-use digital gaming solutions to motivate persistent adherence to HF self-management behaviors and improve health outcomes among individuals with HF., Trial Registration: ClinicalTrials.gov NCT05056129; https://clinicaltrials.gov/ct2/show/NCT05056129., International Registered Report Identifier (irrid): DERR1-10.2196/45801., (©Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Rachel Tunis, Grace Lee, Angelica Rangel, James Custer, Tom Baranowski, Paul J Rathouz, Miyong T Kim. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.05.2023.)

Purpose: The purpose of this study is to use text-mining methods to examine the dominant sources of online information and content about continuous glucose monitors (CGMs). Because the internet is the most popular source for health information, it is important to understand what is being said about CGMs in online sources of information., Methods: A text miner, algorithmic-driven statistical program was used to identify the main sources of online information and topics on CGMs. Content was limited to English and was posted from August 1, 2020, to August 4, 2022. Using Brandwatch software, 17 940 messages were identified. After cleaning, there were 10 677 messages in final analyses conducted using SAS Text Miner V.12.1 software., Results: The analysis identified 20 topics that formed 7 themes. Results show that most online information comes from news sources and focuses on the general benefits of CGM use. Beneficial aspects ranged from improvements in self-management behaviors, cost, and glucose levels. None of the themes mentioned changes to practice, research, or policies related to CGM., Conclusions: To improve diffusion of information and innovations going forward, novel ways of information sharing should be explored, such as diabetes specialist, provider, and researcher engagement in social media and digital storytelling.

Given the importance of healthy eating in the later years of life, the present study examined factors associated with dietary risks in older Korean Americans. We hypothesized that dietary risks would be associated with sociodemographic disadvantages, adverse health conditions, and limited sociocultural resources. Dietary risks were assessed with a scale covering five behavioral and situational risk factors (eating alone, skipping meals, functional challenges, oral health problems, and financial difficulties). Analyses of the data from the Study of Older Korean Americans ( N  = 2,150) showed that the sample on average had 1.13 risks ( SD  = 1.31), eating alone having the highest frequency (35.6%). Supporting the hypothesis, higher levels of dietary risks were found in individuals with sociodemographic disadvantages, poorer physical and mental health status, smaller social networks, and lower acculturation. Findings suggest concerted efforts to promote dietary behaviors and call attention to older immigrants who are socially and culturally isolated.

Objectives: We identified types of family relationships of older Korean Americans and examined how the mental health benefit of friend networks might be conditioned by family type., Methods: Data were from 2,070 participants in the Study of Older Korean Americans, a multistate survey of Korean immigrants aged 60 and older (Mage = 73.3, standard deviation [SD] = 8.01). To identify family types, latent profile analysis (LPA) was performed with marital status, living arrangement, family network, positive and negative interactions with family members, and family mistreatment. Linear regression models examined how mental distress was associated with friend networks and family types, as well as their interactions., Results: LPA identified 5 family types: close-knit, intimate but distant, detached, connected but dysfunctional, and dysfunctional. Greater distress was associated with smaller friend networks and belonging to the detached, connected but dysfunctional, and dysfunctional family types in comparison to the close-knit type. The interaction model showed that people in the connected but dysfunctional and dysfunctional groups had a stronger association between friend networks and mental distress than the counterparts in the close-knit group., Discussion: We not only confirmed the health-promoting role of friend networks and the value of a close-knit family but also found that the benefit of friend networks was pronounced when quality of the family relationship was impaired. Our findings called renewed attention to older immigrants' social convoys of family and friends, suggesting that the enhancement of friend networks could be particularly advantageous for older immigrants with dysfunctional family relationships., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The objective is to examine how older Korean Americans' perceived burdensomeness to their healthcare partners is associated with the characteristics of older adult participants ( egos ) and their healthcare partners ( alters ). Methods: Surveys of 2150 participants in the Study of Older Korean Americans provided ego data. Participants were also asked to list up to three individuals whom they usually asked for help on health-related matters or healthcare use, which generated 3402 alters. Multilevel modeling was conducted to examine the role of the characteristics of egos and alters, as well as their cross-level interactions. Results: Perceived burdensomeness was negatively associated with English-speaking ability and residence in a low Korean density area. Perceived burden was also lowered when emotional support was received from the alters, and this pattern was pronounced among those with multi-comorbidity. Discussion: By identifying older immigrants prone to the sense of burdensomeness, the study suggests strategies to promote their health and healthcare use.

Objectives: To examine associations among perceived racial discrimination, ethnic resources, and mental distress in older Korean Americans. Ethnic resources included ethnic identity (how closely individuals identify themselves with other members of the same ethnic background) and sense of community (individuals' feelings of belonging to their ethnic group). We examined the direct effect of perceived racial discrimination and these ethnic resources, as well as their interactions, hypothesizing that mental distress associated with perceived racial discrimination would be reduced by ethnic resources., Design: Using survey data from the Study of Older Korean Americans ( N  = 2,150), linear regression models of mental distress were examined for direct and interactive roles of perceived racial discrimination and ethnic resources., Results: Mental distress was directly associated with perceived racial discrimination ( B  = 1.90, SE  = .20, p  < .001), ethnic identity ( B  = -.41, SE  = .13, p  < .01), and sense of community ( B  = -.45, SE  = .12, p  < .001). Perceived racial discrimination interacted significantly with sense of community ( B  = -1.86, SE  = .28, p  < .001). Subgroup analyses suggested that in the context of experiencing racial discrimination, a high sense of community can serve as a buffer against mental distress., Conclusions: Ethnic resources are a benefit in coping with experiences of discrimination. The moderating role of sense of community suggests the value of fostering social capital in ethnic communities to protect and promote older immigrants' mental health.

Background: Limited English proficiency (LEP) of dementia caregivers poses a critical barrier to these caregivers' access to evidence-based interventions. In an effort to make such interventions available and accessible to dementia caregivers with LEP, in the present study we use Barrera and colleagues' (2011) three-step model of cultural adaptation: (1) information gathering, (2) preliminary adaptation, and (3) full adaptation. Selecting Korean Americans as a target group and the Savvy Caregiver Program (SCP) as a target intervention, we demonstrate the sequential process of cultural adaption and report the outcomes on feasibility and acceptability., Methods: Preliminary adaptation with linguistic attunement was conducted by translating the SCP manual into Korean and certifying two lay individuals who were bilingual in English and Korean as Savvy trainers. The 6-week online SCP program was delivered by the two trainers in Korean with six to seven caregiver participants per trainer (N = 13). Feasibility and acceptability of the SCP for both caregiver participants and trainers were assessed using mixed methods, and their data then informed full adaptation., Results: Findings not only showed the initial efficacy of the linguistically attuned SCP but also suggested areas for further modification. Data-driven assessment yielded a list of recommended changes for full adaptation, which was reviewed by the SCP developer to ensure fidelity and by community and research partners to confirm contextual and cultural relevance., Conclusions: The adopted changes are broadly summarized as representing logistical, technical, and cultural issues. Given our refined set of educational materials and implementation guidelines, we discuss future directions for research and development., (© 2022. The Author(s).)

C-terminal lysine (CTK) is often classified as a potential critical quality attribute for therapeutic antibodies being developed for subcutaneous (SC) administration because of its potential to impact antibody SC bioavailability/pharmacokinetics (PK). This classification both inflates development costs and increases comparability risks for SC administration of antibodies. However, prior risk assessments of CTK have not fully considered biotransformation of CTK in the SC space, which may play an important role given that circulating carboxypeptidases in humans rapidly process CTK on intravenously administered antibodies. Here, CTK biotransformation in biofluid derived from human SC space was investigated. The representative fluid from the human SC space was sampled from 10 healthy human subjects using the suction blister method. Glycosylated antibody containing high levels of CTK (expressed using a carboxypeptidase D CRISPR/Cas9 knockout CHO cell line) was incubated in the collected suction blister fluids (SBFs), recovered using cognate antigen pulldowns, and characterized for remaining CTK levels using intact and reduced liquid chromatography-mass spectrometry (LC-MS) analysis. CTK processing (i.e., carboxypeptidase activity) was evident in all SBF and exhibited first-order kinetics with rate constants of 2.18 ± 0.57 d -1 (at 37 °C). PK simulations that integrated CTK processing pathways and their associated rate constants were subsequently performed using a range of clinically observed PK parameters for therapeutic antibodies, including atezolizumab- and pertuzumab-specific parameters. The impact of CTK content (even up to 100%) on SC PK outcomes such as bioavailability and C trough were modest (<14%) for all combinations of PK parameters tested in the sensitivity analysis. This study forms the cornerstone data package for derisking CTK as a PK liability for antibody SC programs and highlights the usefulness of fully considering biotransformation during product quality criticality assessments.

Assessing drug permeability across the blood-brain barrier (BBB) is important when evaluating the abuse potential of new pharmaceuticals as well as developing novel therapeutics that target central nervous system disorders. One of the gold-standard in vivo methods for determining BBB permeability is rodent log BB; however, like most in vivo methods, it is time-consuming and expensive. In the present study, two statistical-based quantitative structure-activity relationship (QSAR) models were developed to predict BBB permeability of drugs based on their chemical structure. The in vivo BBB permeability data were harvested for 921 compounds from publicly available literature, non-proprietary drug approval packages, and University of Washington's Drug Interaction Database. The cross-validation performance statistics for the BBB models ranged from 82 to 85% in sensitivity and 80-83% in negative predictivity. Additionally, the performance of newly developed models was assessed using an external validation set comprised of 83 chemicals. Overall, performance of individual models ranged from 70 to 75% in sensitivity, 70-72% in negative predictivity, and 78-86% in coverage. The predictive performance was further improved to 93% in coverage by combining predictions across the two software programs. These new models can be rapidly deployed to predict blood brain barrier permeability of pharmaceutical candidates and reduce the use of experimental animals., Competing Interests: Author KC was employed by the Leadscope Inc; Author SC was employed by the MultiCASE Inc. LS reports that she is the co-Principal Investigator on two Research Collaboration Agreements (RCAs) between the US Food and Drug Administration’s Center for Drug Evaluation and Research, and Leadscope Inc., and MultiCASE Inc., respectively. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Faramarzi, Kim, Volpe, Cross, Chakravarti and Stavitskaya.)

Purpose: The purpose of this study was to investigate the health status and needs of the Asian American/Pacific Islander (AAPI) population with diabetes in Texas., Methods: This was a cross-sectional secondary analysis of data collected from the Behavioral Risk Factors Surveillance System in Texas from 2015 to 2019 for non-Hispanic White (NHW) and AAPI adults., Results: Although the overall crude diabetes prevalence was lower in AAPI adults, age-adjusted diabetes prevalence was higher than in NHWs. Significant risk factors associated with diabetes in the AAPI group included being male, marital status, lower education levels, lower income, being overweight/obese, and having a sedentary lifestyle. Engagement in self-management activities (checking blood glucose, checking feet, attending a diabetes management course) was lower in AAPIs than in NHWs., Conclusions: Given stiff barriers to adequate screening and self-management support in diabetes care among ethnic populations such as AAPIs, targeted efforts to improve diabetes screening and effective care are warranted. Because today's AAPI populations are predominantly first-generation immigrant groups who suffer from language barriers, efforts should be made to develop health surveys in multiple languages for wider inclusion of understudied groups like AAPIs in diabetes-related research.

Objectives: To examine the cross-sectional association of linguistic adaptation with cognitive function, as well as its interactions with sociodemographic and health profiles in older Chinese and Korean immigrants in the U.S., Methods: Using harmonized data ( N = 5063) from the Population Study of Chinese Elderly (PINE) and the Study of Older Korean Americans (SOKA), we examined between- and within-group differences in the role of linguistic adaptation (English use in older Chinese Americans and English proficiency in older Korean Americans) in cognitive function., Results: The positive association between linguistic adaptation and cognitive function was common in both groups. We also found that the relationship was pronounced among subgroups with the underlying linguistic and cognitive vulnerabilities (i.e., the very old, women, those with low education, and newly immigrated individuals)., Discussion: Findings show the importance of linguistic adaptation in older immigrants' cognitive health and suggest a need for targeted interventions for high-risk groups.

Background: Nurse scientists have significantly contributed to health equity and ensuring cultural tailoring of interventions to meet unique needs of individuals. Methodologies for cultural tailoring of self-mangament interventions among marginalized populations have limitedly accommodated intersectionality and group heterogeneity when addressing health needs., Purpose: Identify methodological limitations in cultural tailoring of interventions among priority populations and issue recommendations on cultural elements that researchers can target to ensure valid cultural tailoring approaches., Methods: Synthesis of literature on health equity, self-management, and implementation and dissemination research., Findings: Among priority populations, intersectionality and group heterogeneity has made group-based cultural tailoring approaches less effective in eliciting desirable health outcomes. Precision health methodology could be useful for cultural tailoring of interventions due to the methodology's focus on individual-level tailoring approaches., Discussion: We offer ways to advance health equity research using precision health approaches in cultural tailoring through targeting unique elements of culture and relevant psychosocial phenotypes., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To investigate the variance in 90-day complication, emergency department (ED) visit, revision, and readmission rates between the Latarjet procedure (LP) performed as a primary procedure for the treatment of recurrent shoulder instability associated with critical levels of glenohumeral bone loss and the LP performed as a salvage surgical procedure after failed arthroscopic instability repair (FAIR)., Methods: Patients who underwent a primary LP from 2016-2021 in a single surgeon's practice were identified and divided into 2 cohorts based on the indication for surgery: primary LP for critical bone loss (unipolar or bipolar) (LP-PBL) or LP as salvage surgery for FAIR (LP-FAIR). Patients without a minimum follow-up period of 90 days were excluded. Chart review was conducted to analyze the prevalence of complications, ED visits and/or admissions, and secondary procedures in the 90-day postoperative period. Radiographic images were reviewed to evaluate for graft and/or hardware failure. An unpaired t test and the Fisher exact test were used to compare the 2 groups regarding continuous and categorical data, respectively, and the significance level was set at P < .05., Results: The final sample sizes consisted of 54 patients in the LP-PBL group and 23 patients in the LP-FAIR group. In the postoperative period, 4 complications were observed in the first 90 days. These included complex regional pain syndrome (n = 1) and superficial wound dehiscence (n = 1) in the LP-PBL cohort. Superficial suture abscess (n = 1) and audible crepitation (n = 1) were observed in the LP-FAIR cohort. There was 1 secondary intervention (arthroscopic debridement) in the LP-FAIR cohort. No statistically significant difference in complication rates, ED visits or admissions, or secondary procedures was found between the LP-PBL and LP-FAIR groups., Conclusions: The results of this study indicate that the 90-day complication, ED visit, revision, and readmission rates after open LP are low irrespective of the extent of glenoid or bipolar bone loss and history of arthroscopic instability repair., Level of Evidence: Level III, retrospective cohort study., (© 2022 The Authors.)

Background: The purpose of our study was to examine the clinical outcomes after arthroscopic scapulothoracic bursectomy for the treatment of scapulothoracic bursitis at a minimum of 2-year follow-up., Methods: Twenty patients who underwent arthroscopic scapulothoracic bursectomy for the treatment of symptomatic snapping scapula syndrome were identified from a single surgeon's database. Patients were indicated for surgery if their symptoms persisted for more than 6 months and if they failed nonoperative treatment. Acquired data included patient demographics, shoulder range of motion, American Shoulder and Elbow Surgeon score, visual analog scale scores for pain, and the following Patient-Reported Outcomes Measurement Information System scores: Upper Extremity Computer Adaptive Test Version 2.0, pain intensity, and pain interference scores. Patient satisfaction and subjective shoulder value were also recorded out of 100. Fisher's test and unpaired t tests were performed for statistical analysis, and P values <.05 were considered significant., Results: A total of 20 patients (24 scapulae) were included in our study, with an average follow-up period of 44 (range: 27-91) months. The mean postoperative Patient-Reported Outcomes Measurement Information System scores for Upper Extremity Computer Adaptive Test Version 2.0, pain interference, and pain intensity were 44.2 ± 10.7, 50.9 ± 9.5, and 42.1 ± 9.5, respectively. The mean postoperative American Shoulder and Elbow Surgeon score was 79.0 ± 21.5, and the mean subjective shoulder value was 82.7 ± 12.9. Visual analog scale pain levels showed a significant decrease from 4.95 ± 2.26 preoperatively to 2.27 ± 2.7 ( P  < .05) postoperatively. There was no significant difference in shoulder range of motion after surgery. The mean patient satisfaction was 72.9, with 65% (13/20) of patients reporting satisfaction levels ≥ 80%. Two patients did not report the resolution of their symptoms and required revision surgery., Conclusion: Arthroscopic treatment of scapulothoracic bursitis is a safe, reliable technique that is effective in providing symptomatic relief with a low rate of recurrence, with most patients reporting a significant reduction in periscapular pain., (© 2022 The Authors.)

There is a long tradition of incorporating patient-reported outcomes (PROs) into nursing research and practice. Classical Test Theory (CTT) has been the traditional approach used to develop and refine PROs. Item response theory (IRT) offers promise for addressing measurement problems that have been difficult to solve using CTT. This paper presents foundational concepts in IRT to illustrate how it can be used to improve the development and refinement of PRO measures, with emphasis on interpreting key IRT parameters., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Scope: Garcinia cambogia (G. cambogia) is known to have antiobesity effects. In this study, the therapeutic effects of G. cambogia on glucose homeostasis in obesity-induced diabetes are explored and the underlying mechanisms are investigated., Methods and Results: C2C12 myotubes are treated with G. cambogia; glucose uptake, intracellular Ca 2+ levels, and related alterations in signaling pathways are examined. High-fat diet (HFD)-fed mice are administered G. cambogia for 8 weeks; oral glucose tolerance is evaluated, and the regulation of identified targets of signaling pathways in quadriceps skeletal muscle are examined in vivo. G. cambogia increases glucose uptake in C2C12 myotubes and induces the upregulation of AMPK, ACC, and p38 MAPK phosphorylation. Notably, G. cambogia markedly elevates both intracellular Ca 2+ levels, activating CaMKII, a Ca 2+ -sensing protein, and TBC1D4-mediated GLUT4 translocation, to facilitate glucose uptake. Furthermore, high-glucose-induced inhibition of glucose uptake and signal transduction is reverted by G. cambogia. In an HFD-induced diabetes mouse model, G. cambogia administration results in significant blood glucose-lowering effects, which are attributed to the regulation of targets that have been identified in vitro, in quadricep skeletal muscle., Conclusion: These findings provide new insights into the mechanism by which G. cambogia regulates glucose homeostasis in obesity-induced diabetes., (© 2022 Wiley-VCH GmbH.)

Objectives: To investigate the relationship between cognitive performance and cognitive health appraisals across non-Hispanic White, non-Hispanic Black, and Hispanic older adults in the United States and to explore within-group variations by examining interactions between cognitive performance and background and health variables., Method: The sample ( N  = 3,099) included 2,260 non-Hispanic White, 498 non-Hispanic Black, and 341 Hispanic adults aged 65 or older, from the 2016-2017 Harmonized Cognitive Assessment Protocol. Regression models of cognitive health appraisals, indicated by self-rated cognitive health, were examined in the entire sample and in racial and ethnic subgroups to test direct and interactive effects of cognitive performance, indicated by the Mini-Mental State Examination (MMSE)., Results: The regression model for the entire sample showed direct effects of cognitive performance and race/ethnicity on cognitive health appraisals, as well as a significant interaction between cognitive performance and being non-Hispanic Black. Cognitive performance and cognitive health appraisals were positively associated in non-Hispanic Whites but not significantly associated in non-Hispanic Blacks. Our subsequent analysis within each racial/ethnic group showed that the effect of cognitive performance in non-Hispanic Blacks and Hispanics became either reversed or nonsignificant when background and health variables were considered. Modification by age or chronic medical conditions in each racial and ethnic group was also observed., Conclusion: Overall, these findings suggest that perceptions and appraisals of cognitive health vary by race and ethnicity and hold implications for how these differences should be considered in research and practice with diverse groups of older adults.

Background: As the population ages and more people are affected by multiple chronic conditions, the prevalence of Peripheral Neuropathy (PN) has also rapidly increased. This swift rise in PN leaves clinicians and patients challenged by a lack of consistent diagnosis and treatment guidelines., Purpose: To assist those affected by PN, it is imperative to understand the breadth of symptoms, experiences, and factors related to the quality of life. The primary aims of this study are to (1) characterize the symptoms of PN in a nationwide sample; (2) discern differences in symptom clusters, given perceived causes of PN; and (3) identify significant physiological symptoms related to the quality of life for people with PN., Methods: An online survey of people in online PN support groups. Participants were recruited primarily via an open request sent to recipients of web-based communications from nationally recognized online PN support groups. Inclusion criteria were as follows: Self-reported diagnosis of PN, ability to read English or Spanish, residence in the U.S., and age ≥ 18 years., Results: A total of 608 individuals with PN were included in the analysis. This sample represents 49 U.S. states and the District of Colombia; 221 were male and 387 female. Their disease severity and etiology were similar to previously reported information on this population, with 53.3% of respondents suffering from PN without a known cause. Among known causes, diabetes was the most common (19.6%), followed by chemotherapy (6.9%) and autoimmune diseases (3.6%). Factors affecting the quality of life among people with PN included lower extremity mobility, upper extremity mobility, sleep disturbance, depressive symptoms, and patient activation., Competing Interests: None of the authors disclose any conflicts of interest. The study was supported by one research grant from the Neuropathy Alliance of Texas and two grants from the National Institute of Nursing Research (P30, NR015335), the Center for Transdisciplinary Collaborative Research in Self-management Science at The University of Texas at Austin School of Nursing, and Precision Health Intervention Methodology Training in Self-Management of Multiple Chronic Conditions. (NIH/NR 1T32 NR019035). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other supporters.

Background: With the accelerated spread of COVID-19 and current shelter-in-place orders from many local governments, African American (AA) communities see to be more vulnerable as emerging data show disproportionate rates of infection and mortality among AAs across the nation., Objectives: In a sample of AA church members, to conduct a rapid community assessment during the early phase of the coronavirus disease 2019 pandemic., Methods: Our community-based participatory research team, partnering with the local AA church community and including trained lay health workers, conducted the assessment via telephone and online., Results: Although most participants reported high confidence regarding recommendations for physical distancing, more than 60% reported elevated anxiety and stress, and 10% indicated that they needed more information about staying healthy and safe during the pandemic., Conclusions: Community-based participatory research with lay health workers is an effective method to implement a community needs assessment, problem-solve with community members, and build community health infrastructure during a public health crisis.

Background: Apoptosis and autophagy are known to be correlated with the extent of damage in torn rotator cuffs, and there is no biological evidence for self-recovery or healing of the rotator cuff tear., Purpose: To establish in a rat model of partial- and full-thickness rotator cuff tears how a glycogen synthase kinase 3β (GSK-3β) inhibitor affects the expression of apoptotic and autophagic markers., Study Design: Controlled laboratory study., Methods: Twelve-week-old Sprague Dawley rats were divided into 3 groups (n = 16 per group). Group 1 acted as the control, with no treatment; group 2 received partial-thickness (right side) and full-thickness (left side) rotator cuff tears only; and group 3 received the same rotator cuff injuries, with GSK-3β inhibitor injected afterward. The tendons from each group were harvested 42 days after surgery. Evaluation of gene expression, immunohistochemistry, and TUNEL staining (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) were performed for the following markers: caspases 3, 8, and 9 as well as Bcl-2 (B-cell lymphoma 2); BAX (Bcl-2-associated X protein); beclin 1; p53; and GSK-3β; which represented apoptotic and autophagic reactions. Statistical analysis was performed using 1-way analysis of variance., Results: In the group 2 rats with partial- and full-thickness tears, there were significant increases in the mRNA levels (fold changes) of all 8 markers as compared with group 1 (control). All these increased markers showed significant downregulation by the GSK-3β inhibitor in partial-thickness tears. However, the response to the GSK-3β inhibitor in full-thickness tears was not as prominent as in partial-thickness tears. The number of TUNEL-positive cells in group 2 (partial, 35.08% ± 1.625% [mean ± SE]; full, 46.92% ± 1.319%) was significantly higher than in group 1 (18.02% ± 1.036%; P < .01) and group 3 (partial, 28.04% ± 2.607% [ P < .01]; full, 38.97% ± 2.772% [ P < .01]), and immunohistochemistry revealed increased expression of all the markers in group 2 as compared with control., Conclusion: The apoptotic and autophagic activity induced in a rat model of an acute rotator cuff tear was downregulated after treatment with a GSK-3β inhibitor, particularly with partial-thickness rotator cuff tears., Clinical Relevance: A GSK-3β inhibitor may be able to modulate deterioration in a torn rotator cuff., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Funding was received from the National Research Foundation of Korea (research grant to H.J.L.; 2017R1D1A1B0303672). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

To support the implementation of genome-based precision medicine, we developed machine learning models that predict the recurrence of patients with gynecologic cancer in using immune checkpoint inhibitors (ICI) based on clinical and pathologic characteristics, including Lynch syndrome-related screening markers such as immunohistochemistry (IHC) and microsatellite instability (MSI) tests. To accomplish our goal, we reviewed the patient demographics, clinical data, and pathological results from their medical records. Then we identified seven potential characteristics (four MMR IHC [ MLH1, MSH2, MSH6, and PMS2 ], MSI, Age 60, and tumor size). Following that, predictive models were built based on these variables using six machine learning algorithms: logistic regression (LR), support vector machine (SVM), naive Bayes (NB), random forest (RF), gradient boosting (GB), and extreme gradient boosting (EGB) (XGBoost). The experimental results showed that the RF-based model performed best at predicting gynecologic cancer recurrence, with AUCs of 0.818 and 0.826 for the 5-fold cross-validation (CV) and 5-fold CV with 10 repetitions, respectively. This study provides novel and baseline results about predicting the recurrence of gynecologic cancer in patients using ICI by using machine learning methods based on Lynch syndrome-related screening markers.

Background: The age of adolescents' sexual initiation is decreasing worldwide. Early sexual initiation has been reported to affect social, physical, and mental health, but little is known about the relationship between the timing of sexual initiation and suicidal ideation., Purpose: This study was designed to identify the association between the timing of sexual initiation and suicidal ideation by gender., Methods: This cross-sectional study used data from South Korea's Youth Health Behavior Online Survey for 2016. Data on first- to 12th-grade students (N = 10,810) were analyzed using descriptive statistics, χ2 tests, and hierarchical logistic regression., Results: The results revealed a significant relationship between early sexual initiation and suicidal ideation among both boys and girls. This relationship remained significant after controlling for confounding variables that are known to affect suicidal ideation, including perceived stress, hopelessness, school grades, and sociodemographic characteristics. The risk of suicidal ideation was higher among students who first experienced sex in earlier grades (before the ninth grade) and was also higher in girls than in boys., Conclusions/implications for Practice: Health providers should be aware of the potentially higher risk of suicidal behavior among adolescents after early sexual initiation. Given the extreme sensitivity and vulnerability of this target population, a multidisciplinary school- or community-based intervention program to promote the mental health of affected individuals and the general student population is warranted., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Hepatotoxicity is one of the most frequently observed adverse effects resulting from exposure to a xenobiotic. For example, in pharmaceutical research and development it is one of the major reasons for drug withdrawals, clinical failures, and discontinuation of drug candidates. The development of faster and cheaper methods to assess hepatotoxicity that are both more sustainable and more informative is critically needed. The biological mechanisms and processes underpinning hepatotoxicity are summarized and experimental approaches to support the prediction of hepatotoxicity are described, including toxicokinetic considerations. The paper describes the increasingly important role of in silico approaches and highlights challenges to the adoption of these methods including the lack of a commonly agreed upon protocol for performing such an assessment and the need for in silico solutions that take dose into consideration. A proposed framework for the integration of in silico and experimental information is provided along with a case study describing how computational methods have been used to successfully respond to a regulatory question concerning non-genotoxic impurities in chemically synthesized pharmaceuticals.

Objectives: Inspired by the notion of double jeopardy positing the dual disadvantage in the coexistence of different sources of vulnerability, the present study examined health risks posed by social and linguistic isolation in older Korean Americans., Design: A cross-sectional study, using a four-cell classification to compare isolation types (no isolation, social isolation only, linguistic isolation only, and dual isolation) and to examine their impacts on physical (self-rated health), mental (mental distress), and cognitive (cognitive performance) health., Setting and Participants: Data are from the Study of Older Korean Americans survey of Korean immigrants aged 60 or older (n = 2032), conducted in five states in the United States (California, New York, Texas, Hawaii, and Florida)., Measurement: Social isolation was indexed by the Lubben Social Network Scale-6; linguistic isolation, by a question on English-speaking ability. Physical, mental, and cognitive health were indicated by a single-item self-rating of health, the Kessler Psychological Distress Scale 6, and the Mini-Mental State Examination, respectively., Results: The dual-isolation group exhibited notable sociodemographic and health disadvantages. The odds of having fair/poor health, mental distress, and cognitive impairment were 2.21-3.17 times higher in the dual-isolation group than in the no-isolation group., Conclusion: Our findings confirm that both social relationships and language proficiency are key elements for older immigrants' social connectedness and integration, the deprivation of which puts them at heightened risk in multiple dimensions of health., (© 2021 The American Geriatrics Society.)

The ICH M7 (R1) guideline recommends the use of complementary (Q)SAR models to assess the mutagenic potential of drug impurities as a state-of-the-art, high-throughput alternative to empirical testing. Additionally, it includes a provision for the application of expert knowledge to increase prediction confidence and resolve conflicting calls. Expert knowledge, which considers structural analogs and mechanisms of activity, has been valuable when models return an indeterminate (equivocal) result or no prediction (out-of-domain). A retrospective analysis of 1002 impurities evaluated in drug regulatory applications between April 2017 and March 2019 assessed the impact of expert review on (Q)SAR predictions. Expert knowledge overturned the default predictions for 26% of the impurities and resolved 91% of equivocal predictions and 75% of out-of-domain calls. Of the 261 overturned default predictions, 15% were upgraded to equivocal or positive and 79% were downgraded to equivocal or negative. Chemical classes with the most overturns were primary aromatic amines (46%), aldehydes (45%), Michael-reactive acceptors (37%), and non-primary alkyl halides (33%). Additionally, low confidence predictions were the most often overturned. Collectively, the results suggest that expert knowledge continues to play an important role in an ICH M7 (Q)SAR prediction workflow and triaging predictions based on chemical class and probability can improve (Q)SAR review efficiency., (Copyright © 2021. Published by Elsevier Inc.)

Guided by the models of health assessment and social determinants of health, we examined predictors of self-rated physical, mental, oral, and cognitive health of older Korean immigrants. Data came from the Study of Older Korean Americans (SOKA; N = 2,061, Mean age = 73.2). Multivariate regression models of self-ratings of health were tested with health indicators (both domain-specific and other health indicators including chronic disease, functional disability, mental distress, problems with teeth or gums, and cognitive function) and sociocultural factors (acculturation, social network, and ethnic community social cohesion). For self-rated physical, mental, and oral health, indicators specific to the targeted domain played a primary role, with those of other health domains playing a secondary role. Acculturation and social network were significant predictors of all four measures. Findings highlight the importance of holistic health assessment that considers a wide range of health domains as well as sociocultural contexts.

Objectives: The gap between mental health needs and service use in racial/ethnic minorities continues to be a major public health concern. Focusing on older Korean immigrants, the present study examined linkages among mental distress, self-rated mental health (SRMH), and the use of professional mental health services. We hypothesized that SRMH would play a mediating role in the relationship between mental distress and the use of professional mental health services., Method: Using data from the Study of Older Korean Americans (SOKA; N  = 2,150, Mean age = 73.4), the direct and indirect effect models were tested., Results: Nearly 30% of the sample fell within the category of experiencing mental distress, but only a small proportion (5.7%) had used professional mental health services. Supporting our hypothesis, the pathway from mental distress to the use of professional mental health services was influenced by an individual's subjective perception of mental health status: the indirect effect of mental distress on service use through SRMH (.04 [.01]) was significant (bias-corrected 95% confidence interval for the indirect effect = .02, .06)., Conclusion: The findings of this study not only contribute to our understanding of help-seeking processes in a group at high mental health risk but also suggest avenues to promote their use of mental health services.

Background: The incidence of breast cancer among South Korean women, a historically low-risk population, has increased over the past 3 decades, with marked changes in socioeconomic environment by birth cohort., Objectives: We investigated associations between breast cancer risk and reproductive factors as well as the impact of birth cohort in those associations., Method: This was a cross-sectional study of data from the Korea National Health and Nutrition Examination Survey for 2013-2016. Data from 10 012 parous women 30 years or older were analyzed using descriptive statistics and Cox multivariate regression after adjusting for socioeconomic status, educational level, occupation, and birth cohort., Results: Of the reproductive factors considered-age at menarche, number of pregnancies, age at first birth, age at last birth, breastfeeding duration, and use of oral contraceptives-only age at menarche was associated with breast cancer risk. Higher educational level, not having an occupation, and younger birth cohort were also associated with increased risk of breast cancer, with birth cohort the strongest of these impact factors., Conclusion: Whereas the relationship between reproductive factors and breast cancer risk was relatively weak, birth cohort was the most important risk factor for breast cancer., Implications for Practice: The results provide a basis and a rationale for developing birth cohort-based clinical guidelines for breast cancer prevention and early detection, treatment, and survivorship. These findings should also be useful to researchers in other countries experiencing rapid changes in breast cancer incidence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To examine predictors of membership in discordant groups identified by subjective and objective measures of cognitive function. Methods: Participants in the Study of Older Korean Americans ( N = 2046) were classified according to their subjective cognitive ratings ( excellent / very good / good vs. fair / poor ) and Mini-Mental State Examination scores (normal cognition vs. cognitive impairment), yielding two discordant groups: (1) positive ratings but cognitive impairment and (2) negative ratings but normal cognition. Logistic regression models examined how the discordant group membership was associated with personal resources. Results: Among those with positive cognitive ratings, the odds of belonging to the discordant group were associated with low personal resources (advanced age and lower levels of education, acculturation, and knowledge about Alzheimer's disease). However, an opposite pattern was observed among those with negative ratings. Discussion: The pattern of discordance suggests ways to promote early detection of cognitive impairment and close the gap in cognitive health care.

While free thiols in monoclonal antibodies (mAbs) have been extensively characterized by in vitro studies to probe its effect on antibody function and stability, their in vivo biotransformation has not been comprehensively studied. In this study, a panel of five recombinant IgG1 mAbs with elevated free thiols in the VH, VL, and CH2 domains were intravenously administered into Wistar rats. In vivo biotransformation of thirty-five free thiol sites in total (7 disulfide pairs in VL, CL, VH, CH1, HH, CH2, CH3 domains across the 5 mAbs) were monitored using a denaturing differential isotopic tagging procedure on immunopurified timepoints followed by LC-MS of tryptic digests. The free thiol levels in two VH domain and one CH2 domain disulfide sites decreased in vivo following first order kinetics. Free thiol levels of the remaining 32 sites were remarkably stable in vivo. Further analytical characterization highlighted a positive association between a free thiol's solvent accessibility and a free thiol's reoxidation propensity. The data and discussion presented here shed valuable insights into the in vivo fate of free thiols in several recombinant IgG1s and its implications for free thiols as a product quality attribute in therapeutic mAb products., (Copyright © 2021 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the therapeutic effect of local photothermal (PT) heating on suppression of stent-induced granulation tissue formation in mouse colon., Materials and Methods: A gold nanoparticle (GNP)-coated self-expandable metallic stent (SEMS) was prepared using a two-step synthesis process for local PT heating under near-infrared laser irradiation. Twenty-four mice were randomly divided into two groups of 12 and subjected to SEMS placement in the colon. Group A received a GNP-coated SEMS without local heating and Group B received a GNP-coated SEMS and underwent local heating at 55°C after SEMS placement. The therapeutic effect of local heating was assessed by comparing the histopathological, immunohistochemical, and endoscopic results., Results: Four mice were excluded because of stent migration (n = 3, group B) or death (n = 1, group A). Stent-induced granulation tissue-related variables were significantly lower in group B than in group A (p < 0.001). In vivo endoscopic images, 4 weeks after stent placement, showed granulation tissue formation over the wire mesh in group A and relatively good patency of the stented colon with no definite irregularities in group B. There was more vascular endothelial growth factor (VEGF) positivity in group A than in group B., Conclusion: Local PT heating suppresses granulation tissue formation after stent placement in mouse colon., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The present study examined factors associated with the preference for patient-provider ethnic concordance in Asian Americans. Design: With data drawn from the 2015 Asian American Quality of Life Survey ( N  = 2535), a logistic regression model of the preference for patient-provider ethnic concordance was tested with demographic (age, gender, ethnicity, marital status, education), health and access (chronic medical conditions, self-rated health, health insurance coverage), immigration-related (place of birth, length of stay in the US, English proficiency, acculturation), and adverse experience (perceived discrimination, communication problems in healthcare settings) variables. Results: Over half (52.4%) of those in the sample preferred to be treated by a healthcare provider from their own ethnic background. In a multivariate model, the odds for preferring ethnic concordance were 1.52-1.64 times higher among individuals in earlier stages of immigration, language acquisition, and acculturation. Individuals who had experienced communication problems in healthcare settings presented 3.74 times higher odds for preferring ethnic concordance than did counterparts without such experience. Conclusions: The results emphasized the value of paying attention to patient-provider concordance when treating Asian Americans either relatively new to the country or who have had previous problems communicating with health professionals. The findings also provide implications for improving workforce diversity in healthcare delivery and medical education.

Health authorities require that suitable stability of the drug substance be shown in relevant materials of construction. ICH Q1A(R2) explicitly states that "stability studies should be conducted on drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distribution". Stainless steel containers are commonly used for the long-term storage of frozen bulk drug substances (DSs). Hastelloy®-based metal containers are sometimes used due to their higher corrosion resistance and significantly lower iron content to mitigate the potential corrosion-related risks associated with high salt formulations. Despite their benefits, we have found that elevated temperature stability studies in small scale Hastelloy® containers can lead to degradation that is not representative of degradation under typical storage conditions relevant to the manufacturing process. We provide evidence for an oxidation-induced aggregation mechanism that is based on Fenton chemistry with peroxide being supplied by the autoxidation of polysorbate at stress temperatures. Further, variation in the rates of iron leaching between individual small scale containers is shown to be the cause of the variable rates of degradation through strong correlations between leached iron levels and the extents of oxidation and aggregation. The addition of a metal chelator or the removal of polysorbate from the formulation mitigates the oxidation and the non-representative behavior. Extended characterization by LC-MS and 18 O labeled peptide mapping shows that a significant portion of the aggregate formed under these conditions is covalently crosslinked and that the predominant covalent species is either a dityrosine or tyrosine-tryptophan crosslink between an Fc peptide and a Fab peptide. This report is the first time either of these two crosslinks have been reported for antibodies with detailed analytical characterization. Because the behavior observed in these studies is not representative of degradation under typical storage conditions relevant to the manufacturing process, this study demonstrates that small scale stress studies in metal containers should be performed with caution and that extended incubation times can lead to non-representative degradation mechanisms., (Copyright © 2020. Published by Elsevier Inc.)

Background: As the U.S. population grows older and more diverse, self-management needs are increasingly complicated. In order to deliver effective personalized interventions to those suffer from chronic conditions social determinants of health must be considered. Therefore, psychosocial phenotyping holds strong promise as a tool for tailoring interventions based on precision health principles., Purpose: To define psychosocial phenotyping and develop a research agenda that promotes its integration into chronic disease management as a tool for precision self-management interventions., Methods: Since psychosocial phenotyping is not yet used in interventions for self-management support, we conducted a literature review to identify potential phenotypes for chronic disease self-management. We also reviewed policy intervention case reports from the Centers for Medicare and Medicaid Services to examine factors related to social determinants of health in people with chronic illnesses. Finally, we reviewed methodological approaches for identifying patient profiles or phenotypes., Results: The literature review revealed areas within which to collect data for psychosocial phenotyping that can inform personalized interventions. The findings of our exemplar cases revealed that several environmental or key SDOH such as factors realted with economic stability and neighborhood environment have been closely linked with the success of chronic disease management interventions. We elucidated theory, definitions, and pragmatic conceptual boundaries related to psychosocial phenotyping for precision health., Conclusions: Our literature review with case example analysis demonstrates the potential usefulness of psychosocial phenotyping as a tool to enhance personalized self-management interventions for people with chronic diseases, with implications for future research., Competing Interests: None., (AJTR Copyright © 2021.)