Toward Sustaining Web-Based Senior Center Programming Accessibility With and for Older Adult Immigrants: Community-Based Participatory Research Cross-Sectional Study.

BACKGROUND: During the COVID-19 pandemic, many community-based organizations serving Asian Americans pivoted to provide web-based care and social services. Asian American community leaders in the United States Pacific Northwest, including Asian Health & Service Center expressed that there are older immigrant adults who experienced backlash from discrimination, fear, and anxiety owing in part to anti-Asian hate and isolation, including from infection precautions. Pivoting supported staying safe from COVID-19 transmission and anti-Asian hate crimes. OBJECTIVE: This study aims to examine the readiness of diverse groups of older Asian American immigrant adults (Chinese, Koreans, and Vietnamese) to use a web-based senior center, including technology access and telehealth use, and to identify the psychosocial health impacts that a web-based senior center could be positioned to meet. METHODS: A community-based participatory research approach was used to conduct a cross-sectional survey study in an Asian-based health and service center in 2022. We selected surveys from the National Institutes of Health-supported PhenX Toolkit. Analyses were performed using R software. RESULTS: There was an 88.2% (216/245) response rate. Overall, 39.8% (86/216) of participants were Chinese, 25% (54/216) were Korean, and 24.5% (53/216) were Vietnamese. There were significant group differences in mobile data plans (P=.0005). Most had an unlimited mobile data plan (38/86, 44% Chinese; 39/54, 72% Koreans; 25/53, 47% Vietnamese). Significant group differences existed regarding whether they started using a new electronic device to communicate with friends or family after the COVID-19 outbreak (P=.0005); most were Korean participants (31/54, 57%). For written text and audio or video apps, most Chinese participants used WeChat (65/85, 76%; 57/84, 68%, respectively), most Koreans used KakaoTalk (49/54, 91%; 49/54, 91%, respectively), and most Vietnamese used Facebook Messenger for written text (32/50, 64%) and Apple Face Time (33/50, 66%) or Facebook Messenger (31/50, 62%) for audio or video. Significant group differences existed regarding whether to try telehealth (P=.0005); most Vietnamese expressed that they would never consider it (41/53, 77%). Significant group differences existed regarding how well they were able to concentrate (χ22=44.7; P<.0001); Chinese participants reported a greater inability (median 5, IQR 4-6). With regard to difficulties in life experiences (χ22=51; P<.0001), the median was 6 (IQR 5-7) for the Vietnamese group. Significant group differences existed in having had a family/household member's salary, hours, and contracts reduced (P=.0005) and having had a family/household member or friend fallen physically ill (P=.0005)-most Vietnamese (15/53, 28%) and Korean participants (10/53, 19%). CONCLUSIONS: To build an efficacious, web-based senior center with web-based care and social service options, more older adults need access to the internet and education about using technology-enabled communication devices. Addressing the unique psychosocial impacts of the COVID-19 pandemic on each group could improve health equity. The strength of the participating older adults was observed and honored.

Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function.

A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.73m2 (Cohort A) and 30-60 mL/min/1.73m2 (Cohort B). Eight subjects in Cohort A received a YHD1119 75 mg tablet (Y75T) and a YHD1119 150 mg tablet (Y150T) in each period, and eight subjects in Cohort B received a Y75T. Non-compartment analysis and population pharmacokinetic analysis using a one-compartment model with first-order elimination and first-order absorption with lag time were performed. Sixteen subjects completed the study. The geometric mean ratio (GMR) (90% confidence intervals [CI]) for maximum concentration (Cmax), and area under the concentration-time profile from 0 to the last measurable time (AUClast) after Y75T of Cohort B to those of Y75T of Cohort A were 1.2273 (1.0245-1.4701), and 2.4146 (1.8142-3.2138), respectively. The GMR (90% CI) for Cmax, and AUClast after Y75T of Cohort B to those of Y150T of Cohort A were 0.6476 (0.5229-0.8021), and 1.1471 (0.8418-1.5632), respectively. Simulated steady-steady pregabalin concentrations after once-daily Y75T dosing in subjects with eGFR 45 mL/min/1.73 m2 were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m2. The total pregabalin exposure of Y75T in patients with moderate renal impairment was comparable with that of Y150T in subjects with near-normal renal function. Trial Registration: ClinicalTrials.gov Identifier: NCT05012436.

Urinary Profile of Endogenous Gamma-Hydroxybutyric Acid and its Biomarker Metabolites in Healthy Korean Females: Determination of Age-Dependent and Intra-Individual Variability and Identification of Metabolites Correlated With Gamma-Hydroxybutyric Acid.

Gamma-hydroxybutyric acid (GHB), used as a therapeutic and an illegal anesthetic, is a human neurotransmitter produced during gamma-aminobutyric acid (GABA) biosynthesis and metabolism. Potential biomarker metabolites of GHB intoxication have been identified previously; however, reference concentrations have not been set due to the lack of clinical study data. Urinary profiling of endogenous GHB and its biomarker metabolites in urine samples (n = 472) of 206 healthy females was performed based on differences in age and time of sample collection using liquid chromatography-tandem mass spectrometry following validation studies. The unadjusted and creatinine-adjusted urinary concentrations ranges were obtained after urinary profiling. The creatinine-adjusted concentrations of glutamic and succinic acids and succinylcarnitine significantly increased, whereas that of glycolic acid significantly decreased with advancing age. Significant inter-day variation of GABA concentration and intra-day variation of 3,4-dihydroxybutyric acid and succinylcarnitine concentrations were observed. The urinary concentrations of 2,4-dihydroxybutyric acid, succinic acid, and 3,4-dihydroxybutyric acid showed the highest correlation with that of GHB. Data from this study suggest population reference limits to facilitate clinical and forensic decisions related to GHB intoxication and could be useful for identification of biomarkers following comparison with urinary profiles of GHB-administered populations.

An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug.

Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and modelbased analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.

Leaf Carbon Export and Nonstructural Carbohydrates in Relation to Diurnal Water Dynamics in Mature Oak Trees.

Trees typically experience large diurnal depressions in water potential, which may impede carbon export from leaves during the day because the xylem is the source of water for the phloem. As water potential becomes more negative, higher phloem osmotic concentrations are needed to draw water in from the xylem. Generating this high concentration of sugar in the phloem is particularly an issue for the ∼50% of trees that exhibit passive loading. These ideas motivate the hypothesis that carbon export in woody plants occurs predominantly at night, with sugars that accumulate during the day assisting in mesophyll turgor maintenance or being converted to starch. To test this, diurnal and seasonal patterns of leaf nonstructural carbohydrates, photosynthesis, solute, and water potential were measured, and carbon export was estimated in leaves of five mature (>20 m tall) red oak (Quercus rubra) trees, a species characterized as a passive loader. Export occurred throughout the day at equal or higher rates than at night despite a decrease in water potential to -1.8 MPa at midday. Suc and starch accumulated over the course of the day, with Suc contributing ∼50% of the 0.4 MPa diurnal osmotic adjustment. As a result of this diurnal osmotic adjustment, estimates of midday turgor were always >0.7 MPa. These findings illustrate the robustness of phloem functioning despite diurnal fluctuations in leaf water potential and the role of nonstructural carbohydrates in leaf turgor maintenance.

Killers 2.0: NK cell therapies at the forefront of cancer control.

Natural killer (NK) cells are innate cytotoxic lymphocytes involved in the surveillance and elimination of cancer. As we have learned more and more about the mechanisms NK cells employ to recognize and eliminate tumor cells, and how, in turn, cancer evades NK cell responses, we have gained a clear appreciation that NK cells can be harnessed in cancer immunotherapy. Here, we review the evidence for NK cells' critical role in combating transformed and malignant cells, and how cancer immunotherapies potentiate NK cell responses for therapeutic purposes. We highlight cutting-edge immunotherapeutic strategies in preclinical and clinical development such as adoptive NK cell transfer, chimeric antigen receptor-expressing NK cells (CAR-NKs), bispecific and trispecific killer cell engagers (BiKEs and TriKEs), checkpoint blockade, and oncolytic virotherapy. Further, we describe the challenges that NK cells face (e.g., postsurgical dysfunction) that must be overcome by these therapeutic modalities to achieve cancer clearance.