The Impact of Social Vulnerability on Alcohol Consumption and Mortality: A 20-year Age, Sex-stratified Analysis from the Taiwan Longitudinal Study of Aging.

OBJECTIVE: This study aimed to use the Social Vulnerability Index (SVI) to encapsulate the complex and multidimensional nature of social determinants and their influence on alcohol intake and mortality in middle-aged and older individuals. DESIGN: Cohort study. SETTING AND PARTICIPANTS: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with 3945 study participants aged 50 years and older. METHODS: The TLSA questionnaire defined SVI (51 items including living conditions, social support, socially oriented activities of daily living, social engagement and leisure, empowerment of life, satisfaction about life, and socioeconomic status) and alcohol intake (behavior as well as type and frequency of alcohol intake). Multivariate Cox proportional hazard models were used to estimate the association between alcohol intake and mortality, stratified by sex and SVI groups. RESULTS: Men with high social vulnerability and high alcohol intake exhibit an elevated mortality risk [adjusted hazard ratio (aHR), 1.51; 95% CI, 1.01-2.24], whereas notably, women in similar social circumstances but with moderate alcohol intake face a quintupled mortality risk (>35 g/wk; aHR, 5.67; 95% CI, 2.37-13.61). The impact of alcohol and social vulnerability on mortality was more pronounced in men younger than 65. Among them, those with high social vulnerability and moderate (35-140 g/wk; aHR, 2.83; 95% CI, 1.50-5.36) to high (>140 g/wk; aHR, 2.24; 95% CI, 1.15-4.35) alcohol intake was associated with an increased risk of mortality. CONCLUSIONS AND IMPLICATIONS: Various factors throughout the life course of both men and women significantly impact the risk of all-cause mortality due to alcohol intake, underscoring the importance of social vulnerability as a determinant of both alcohol intake behavior and mortality risk.

Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 µg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (ß = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (ß = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (ß = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (ß = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (ß = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (ß = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls. CONCLUSIONS: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

RNA-Based Antipsoriatic Gene Therapy: An Updated Review Focusing on Evidence from Animal Models.

Psoriasis presents as a complex genetic skin disorder, characterized by the interaction between infiltrated immune cells and keratinocytes. Substantial progress has been made in understanding the molecular mechanisms of both coding and non-coding genes, which has positively impacted clinical treatment approaches. Despite extensive research into the genetic aspects of psoriasis pathogenesis, fully grasping its epigenetic component remains a challenging endeavor. In response to the pressing demand for innovative treatments to alleviate inflammatory skin disorders, various novel strategies are under consideration. These include gene therapy employing antisense nucleotides, silencing RNA complexes, stem cell therapy, and antibody-based therapy. There is a pressing requirement for a psoriasis-like animal model that replicates human psoriasis to facilitate early preclinical evaluations of these novel treatments. The authors conduct a comprehensive review of various gene therapy in different psoriasis-like animal models utilized in psoriasis research. The animals included in the list underwent skin treatments such as imiquimod application, as well as genetic and biologic injections, and the results of these interventions are detailed. Animal models play a crucial role in translating drug discoveries from the laboratory to clinical practice, and these models aid in improving the reproducibility and clinical applicability of preclinical data. Numerous animal models with characteristics similar to those of human psoriasis have proven to be useful in understanding the development of psoriasis. In this review, the article focuses on RNA-based gene therapy exploration in different types of psoriasis-like animal models to improve the treatment of psoriasis.

Intrinsic capacity and multimorbidity predicting incident disability-Insights from the I-Lan Longitudinal Aging Study.

OBJECTIVES: This longitudinal cohort study aimed to examine the effect of intrinsic capacity (IC) and multimorbidity on the development of new disabilities. METHODS: The study utilized data from 1,009 participants without disabilities from the I-Lan Longitudinal Aging Study. Multivariable logistic regressions were employed to assess the predictive capability of IC (ranging from 0 to 100) and multimorbidity for incident disability over a 7-year follow-up period. RESULTS: Both low IC (OR 4.9, 95 % CI 2.1-11.1, p < 0.001) and multimorbidity (OR 4.5, 95 % CI 2.2-9.2, p < 0.001) significantly predicted incident disability over the 7-year period. A one-point increase in IC reduced the risk of incident disability by 10 % (OR 0.9, 95 % CI 0.8-0.9, p < 0.001). Among IC subdomains, both better locomotion (OR 0.96, 95 % CI 0.94-0.99, p = 0.014) and psychology (OR 0.97, 95 %CI 0.94-1.00, p = 0.049) significantly reduced the risk of incident disability. Rapid declines in IC significantly predicted incident disability (OR 4.1, 95 % CI 1.8-9.3, p = 0.001), whereas the onset of new multimorbidity or changes in the number of chronic conditions did not demonstrate a significant association with incident disability. The interaction terms between IC and multimorbidity, both categorically (low IC * multimorbidity, p = 0.959) and numerically (IC (per point) * multimorbidity, p = 0.660) were all statistically insignificant. CONCLUSIONS: IC exhibited better predictive capacity for 7-year incident disability compared to multimorbidity, so health care services targeting older adults should adopt an integrated care approach that combines both function- and disease-centric strategies.

The anti-inflammatory activity of flavonoids and alkaloids from Sophora flavescens alleviates psoriasiform lesions: Prenylation and methoxylation beneficially enhance bioactivity and skin targeting.

The herb Sophora flavescens displays anti-inflammatory activity and can provide a source of antipsoriatic medications. We aimed to evaluate whether S. flavescens extracts and compounds can relieve psoriasiform inflammation. The ability of flavonoids (maackiain, sophoraflavanone G, leachianone A) and alkaloids (matrine, oxymatrine) isolated from S. flavescens to inhibit production of cytokine/chemokines was examined in keratinocytes and macrophages. Physicochemical properties and skin absorption were determined by in silico molecular modeling and the in vitro permeation test (IVPT) to establish the structure-permeation relationship (SPR). The ethyl acetate extract exhibited higher inhibition of interleukin (IL)-6, IL-8, and CXCL1 production in tumor necrosis factor-α-stimulated keratinocytes compared to the ethanol and water extracts. The flavonoids demonstrated higher cytokine/chemokine inhibition than alkaloids, with the prenylated flavanones (sophoraflavanone G, leachianone A) led to the highest suppression. Flavonoids exerted anti-inflammatory effects via the extracellular signal-regulated kinase, p38, activator protein-1, and nuclear factor-κB signaling pathways. In the IVPT, prenylation of the flavanone skeleton significantly promoted skin absorption from 0.01 to 0.22 nmol/mg (sophoraflavanone G vs. eriodictyol). Further methoxylation of a prenylated flavanone (leachianone A) elevated skin absorption to 2.65 nmol/mg. Topical leachianone A reduced the epidermal thickness in IMQ-treated mice by 47%, and inhibited cutaneous scaling and cytokine/chemokine overexpression at comparable levels to a commercial betamethasone product. Thus, prenylation and methoxylation of S. flavescens flavanones may enable the design of novel antipsoriatic agents.

Insulin-like growth factor 2 mRNA-binding protein 3 enhanced melanoma migration through regulation of AKT1 and RELA expression.

IMP-3 expression is a poor prognostic factor of melanomas and it promotes melanoma cell migration and invasion by a pathway modulating HMGA2 mRNA expression. We tried to identify other putative targets of IMP-3. We identified putative IMP-3-binding RNAs, including AKT1, MAPK3, RB1 and RELA, by RNA immunoprecipitation coupled with next-generation sequencing. IMP-3 overexpression increased AKT and RELA levels in MeWo cells. siRNAs against AKT1 and RELA inhibited MeWo/Full-length IMP-3 cell migration. IMP-3 knockdown of A2058 cells decreased AKT1 and RELA expression and lowered migration ability. Co-transfection of A2058 cells with AKT1- or RELA-expressing plasmids with IMP-3 siRNA restored the inhibitory effects of IMP-3 knockdown on migration. HMGA2 did not influence AKT1 and RELA expression in melanoma cells. Human melanoma samples with high IMP-3 levels also showed high HMGA2, AKT1 and RELA expression. Our results show that IMP-3 enhances melanoma cell migration through the regulation of the AKT1 and RELA axis.

Enhancing Intrinsic Capacity and Related Biomarkers in Community-Dwelling Multimorbid Older Adults Through Integrated Multidomain Interventions: Ancillary Findings From the Taiwan Integrated Geriatric (TIGER) Trial.

OBJECTIVE: This study aimed to evaluate the efficacy of integrated multidomain interventions and primary health care on intrinsic capacity (IC) and related biomarkers. DESIGN: An ancillary analysis from the Taiwan Integrated Geriatric Care (TIGER) study: a randomized controlled trial. SETTING AND PARTICIPANTS: A total of 398 community-dwelling older adults aged ≥65 years with ≥3 chronic conditions. METHODS: Participants were randomized into the 12-month pragmatic multidomain intervention or usual care groups. The primary outcome was the change in IC and its subdomains (locomotion, cognition, vitality, psychological, and sensory) at baseline and 3-, 6-, 9-, and 12-month follow-ups. Generalized linear mixed models were used to evaluate the multidomain intervention effects on these changes. RESULTS: The intervention arm had greater improvement in IC than the usual care arm (overall difference 1.5; 95% CI 0.5-2.5; P = .005), mainly from subdomains of locomotion (overall difference 1.4; 95% CI 0.5-2.4; P = .004) and cognition (2.9; 95% CI 2.1-3.7; P < .001). Changes in neutrophil-to-lymphocyte ratio (NLR -2.4; 95% CI -3.9 to -0.8, P = .003), serum levels of albumin (35.1; 95% CI 23.1-47.2; P < .001), dehydroepiandrosterone sulfate (DHEA-S 2.8; 95% CI 1.9-3.8; P < .001), free androgen index (FAI 1.5; 95% CI 1.1-1.9; P < .001), and vitamin D (4.0; 95% CI 2.0-6.1; P < .001) were associated with changes in IC over time. CONCLUSIONS AND IMPLICATIONS: The incorporation of multidomain interventions into primary health care significantly enhanced IC over the 12-month program. Changes in NLR, FAI, and serum levels of albumin, DHEA-S, vitamin D were associated with changes in IC over time. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03528005.

Anatomic mapping of acral melanocytic nevi and acral lentiginous melanomas among Taiwanese patients: A retrospective cohort study.

BACKGROUND: The early diagnosis of acral lentiginous melanoma (ALM) contributes to clinical outcomes since ALM can be mistaken for acral melanocytic nevus (AMN). ALM occurrence is reported to correlate with stress-bearing areas, which may assist in differential diagnoses. Our objective is to evaluate the distribution patterns of ALMs and AMNs on the palms and soles among Taiwanese patients. METHODS: A retrospective analysis was performed by reviewing the charts of 1400 patients diagnosed with benign and malignant pigmented lesions confirmed after excisional biopsy at our institution between 2000 and 2022 in Taiwan. Correlations between lesions and clinicopathological factors were analyzed. RESULTS: 309 AMNs and 177 ALMs were included. Mechanical stress was significantly associated with plantar ALMs (weight-bearing area: 92.65 %, arch: 7.35 %, P < 0.001). Significant differences in the distribution patterns were observed for plantar ALMs compared with all AMNs (P < 0.001) and non-atypical AMNs (P < 0.001), but were not observed between palmar AMNs and ALMs. CONCLUSION: Plantar ALMs were most commonly observed on the weight-bearing areas of the soles, distinct from the distribution of all AMNs and of non-atypical AMNs. The distribution features and anatomic mapping of ALMs may facilitate the early clinical diagnosis of ALM.

The Entanglement of Li Capping and Deposition: An Operando Optical Microscopy Study.

Dendrite growth and low Coulombic efficiency impede the practical application of Li-metal batteries. As such, monitoring Li deposition and stripping in real-time is crucial to understanding the fundamental lithium growth kinetics. This work presents an operando optical microscopic technique that enables precise current density control and quantification of Li layer properties (i.e., thickness and porosity) to study Li growth in various electrolytes. We discover the robustness and porosity of the remaining capping layer after the Li stripping process as the critical features governing the subsequent dendrite propagation behavior, resulting in distinct capping and stacking phenomena that affect Li growth upon cycling. While dendrite propagation quickly occurs through the fracture of the fragile Li capping layer, uniform Li plating/stripping can be facilitated by the compact and robust capping layer even at high current densities. This technique can be extended to evaluate dendrite suppression treatments in various metal batteries, providing in-depth information on metal growth mechanisms.

Study on the Application of Nitrogen-Doped Holey Graphene in Supercapacitors with Organic Electrolyte.

We present a facile low-cost method to produce nitrogen-doped holey graphene (N-HGE) and its application to supercapacitors. A composite of N-HGE and activated carbon (AC) was used as the electrode active material in organic-electrolyte supercapacitors, and the performances were evaluated. Melamine was mixed into graphite oxide (GO) as the N source, and an ultra-rapid heating method was used to create numerous holes during the reduction process of GO. X-ray photoelectron spectra confirmed the successful doping with 2.9-4.5 at.% of nitrogen on all samples. Scanning electron micrographs and Raman spectra revealed that a higher heating rate resulted in more holes and defects on the reduced graphene sheets. An extra annealing step at 1000 °C for 1 h was carried out to further eliminate residual oxygen functional groups, which are undesirable in the organic electrolyte system. Compared to the low-heating-rate counterpart (N-GE-15), N-HGE boosted the specific capacity of the supercapacitor by 42 and 22% at current densities of 0.5 and 20 A/g, respectively. The effects of annealing time (0.5, 1, and 2 h) at 1000 °C were also studied. Longer annealing time resulted in higher capacitance values at all current densities due to the minimized oxygen content. Volumetric specific capacitances of 49 and 24 F/cm3 were achieved at current densities of 0.5 and 20 A/g, respectively. For the high-power-density operation at 31,000 W/kg (or 10,000 W/L), an energy density as high as 11 Wh/kg (or 3.5 Wh/L) was achieved. The results indicated that N-HGE not only improved the conductivity of the composite supercapacitors but also accelerated ion transport by way of shortened diffusion paths through the numerous holes all over the graphene sheets.

Intrinsic capacity differs from functional ability in predicting 10-year mortality and biological features in healthy aging: results from the I-Lan longitudinal aging study.

This study aimed to explore the biological features and mortality risk of intrinsic capacity (IC) and functional ability (FA). Based on data from 1839 participants from the I-Lan Longitudinal Aging Study, multivariable Cox proportional hazard models were used to evaluate the predictive ability of IC (range 0-100) and FA (range 0-100) on 10-year mortality. Of 2038 repeated measurements for IC within a 7-year observational period, multivariable logistic regression was used to compare biological features of participants with maintained, improved and rapidly deteriorated IC. A 1-point increased IC value was associated with a 5% (HR 0.95, 95% CI 0.93-0.97, p < 0.001) decrease in mortality risk. Low IC (HR 1.94, 95% CI 1.39-2.70, p < 0.001) was associated with higher mortality risk. Hyperglycemia (OR 1.40, 95% CI 1.09-1.81, p = 0.010), low serum levels of DHEA-S (OR 3.33, 95% CI 1.32-8.41, p = 0.011), and high serum levels of C-reactive protein (OR 1.45, 95% CI 1.05-2.00, p = 0.023) were associated with low IC at baseline. Low serum levels of DHEA-S (middle tertile OR 1.84, 95% CI 1.15-2.95, p = 0.012; lowest tertile OR 2.25, 95% CI 1.34-3.77, p = 0.002) and vitamin D deficiency (OR 1.82, 95% CI 1.02-3.27, p = 0.044) were associated with rapid deterioration of IC. IC and FA predicted 10-year mortality, whereas chronic inflammation, hyperglycemia, and low DHEA-S were associated with low IC status. Low DHEA-S and vitamin D deficiency may be considered as potential biomarkers of rapid IC declines, which implies underlying biological mechanisms of healthy aging.

Transitions in Frailty and 4-Year Mortality Risk in Taiwan Longitudinal Study on Aging.

OBJECTIVES: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed. METHODS: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively. RESULTS: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index). CONCLUSIONS AND IMPLICATIONS: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings.

Operando X-ray Studies of Ni-Containing Heteropolyvanadate Electrode for High-Energy Lithium-Ion Storage Applications.

Ni-containing heteropolyvanadate, Na6[NiV14O40], was synthesized for the first time to be applied in high-energy lithium storage applications as a negative electrode material. Na6[NiV14O40] can be prepared via a facile solution process that is suitable for low-cost mass production. The as-prepared electrode provided a high capacity of approximately 700 mAh g-1 without degradation for 400 cycles, indicating excellent cycling stability. The mechanism of charge storage was investigated using operando X-ray absorption spectroscopy (XAS), X-ray diffraction (XRD), transition X-ray microscopy (TXM), and density functional theory (DFT) calculations. The results showed that V5+ was reduced to V2+ during lithiation, indicating that Na6[NiV14O40] is an insertion-type material. In addition, Na6[NiV14O40] maintained its amorphous structure with negligible volume expansion/contraction during cycling. Employed as the negative electrode in a lithium-ion battery (LIB), the Na6[NiV14O40]//LiFePO4 full cell had a high energy density of 300 W h kg-1. When applied in a lithium-ion capacitor, the Na6[NiV14O40]//expanded mesocarbon microbead full cell displayed energy densities of 218.5 and 47.9 W h kg-1 at power densities of 175.7 and 7774.2 W kg-1, respectively. These findings reveal that the negative electrode material Na6[NiV14O40] is a promising candidate for Li-ion storage applications.

Clinical efficacy of oligonol® supplementation on metabolism and muscle health in middle-aged and older adults: A double-blinded randomized controlled trial.

BACKGROUND: Oligonol® is a low-molecular-weight polyphenol that has biological effects on metabolism in animals. However, little is known about its roles in muscle function and muscle quality in middle-aged and older adults. METHODS: 120 participants were enrolled for study based on 1:1 randomization. Participants in the intervention group were provided 200 mg oligonol® prepared as capsules, and 200 mg placebo (dextrin) was provided in control group. RESULTS: Data from 103 participants (52 in the intervention group and 51 in the control group) were available for analysis. The mean age of all participants was 64.0 ± 8.2 years, and two-thirds of the participants were females. Baseline demographic characteristics, functional assessment, laboratory data and muscle parameters were similar between groups. Hip circumference decreased (p = 0.009) during the study period, and the 6-m walking speed increased (p = 0.001) in women in the intervention group. In contrast, 6-m walking speed, 6-min walking distance and handgrip strength were significantly improved in men in the intervention group, but increased total body fat percentage (p = 0.038) and decreased mid-thigh cross-muscle area (CMA) (p = 0.007) were observed in the control group. Compared to the control group, the 12-week interval change in the percentage of mid-thigh CMA was maintained in men in the intervention group but was significantly decreased in the control group (p = 0.03, 95% CI:0.002-0.05). CONCLUSIONS: Oligonol supplementation (200 mg per day) significantly improved physical performance and muscle mass in men. Further studies are needed to confirm the potential favorable effects of oligonol® supplementation.

Antiperistaltic effect and safety of L-menthol for esophagogastroduodenoscopy in the elderly with contraindication to hyoscine-N-butylbromide.

Hyoscine-N-butylbromide (HBB) is the most used antiperistaltic agent during esophagogastroduodenoscopy (EGD). However, almost half of the elderly have a contraindication to HBB. We aimed to evaluate L-menthol's antiperistaltic effect and safety for EGD in the elderly with contraindication to HBB. This prospective, randomized, double-blind, placebo-controlled study screened 86 elderly patients (≥ 65 years old) scheduled to undergo EGD, and 52 of them with contraindication to HBB were enrolled. The participants were randomized to receive L-menthol (n = 26) or a placebo (n = 26), which was locally sprayed on the gastric antrum endoscopically. The proportion of patients with no or mild peristalsis after medication and at the end of EGD was significantly higher in the L-menthol group (76.9%) than in the placebo group (11.5%, p < 0.001). L-Menthol administration significantly reduced peristaltic grade, improved contraction parameters, and eased intragastric examination relative to the placebo (p < 0.001, respectively). Hemodynamic changes, adverse events, and discomfort levels of patients were similar between the two groups. L-Menthol is an effective and safe alternative antiperistaltic medication for EGD in elderly patients with contraindication to HBB. Further large, randomized trials are required to clarify whether L-menthol can lead to better detection yield in the elderly.Clinical trial registration: The study was registered at ClinicalTrials.gov (NCT04593836).

Six-year transition of physio-cognitive decline syndrome: Results from I-Lan Longitudinal Aging Study.

OBJECTIVES: To explore associations between PCDS, incident dementia and mortality risk and evaluate the potential of its reversibility. METHODS: 963 participants from the I-Lan Longitudinal Aging Study were followed up for 6 years for analysis. A subsample of 513 participants was invited to participate 3 years earlier. The 1.5 standard deviation lower age- and education-matched norms of neuropsychiatric assessments determined cognitive impairment. Weakness and slowness were defined by the Asian Working Group for Sarcopenia 2019. PCDS was defined as cognitive impairment plus mobility impairment, i.e., weakness and/or slowness. RESULTS: The prevalence of PCDS was 19.0% among 1709 participants aged 63.5 ± 9.0 years (from 50 to 90 years) and increased with age (14.7% in people aged 50-64 years, 19.5% in people aged 65-74 years, 36.7% in people aged 75-84 years and 45.5% in people aged ≥ 85 years, p for trend <0.001). 13.6% and 8.3% of participants had improved PCDS conditions in 513 participants at 3-year and in 963 participants at 6-year assessments. Of 118 participants with PCDS at baseline,36 (30.5%) returned to non-PCDS in 6 years. Being female and having good nutrition were potential associated factors. During the mean follow-up period of 5.9 ± 0.9 years, 182 deaths occurred in the 10,065 person-years. PCDS could predict the 6-year risk of mortality (HR 1.56, 95% CI 1.02-2.39, p = 0.012) and 6-year incident dementia (OR 3.42, 95% CI: 1.41-8.29, p = 0.007). CONCLUSIONS: PCDS significantly predict 6-year mortality and 6-year incident dementia. Reversibility of PCDS made it as an optimal target for intervention and prevention.

Arsenic in Drinking Water and Incidences of Leukemia and Lymphoma: Implication for Its Dual Effects in Carcinogenicity.

Arsenic in drinking water has been recognized as carcinogenic to humans and can cause solid cancers of lung, urinary bladder, and skin. Positive associations have also been reported between arsenic ingestion and cancers of kidney, liver and prostate. Nevertheless, arsenic trioxide has been used successfully in the treatment of acute promyelocytic leukemia. Therefore, arsenic might play different roles in the carcinogenesis of solid cancers and hematologic malignancies. The relationship between arsenic in drinking water and the incidences of hematologic malignancies has not been fully investigated. We established a cohort of Taiwanese population and assorted 319 townships of Taiwan into two exposure categories using 0.05 mg/L as the cutoff. Then, we linked these data to the Taiwan Cancer Registry and computed standardized incidence ratios (SIRs) of lymphoma and leukemia by sex, exposure category and time period. The trend of changes in the SIRs over time was assessed, from 1981-1990 to 1991-2000 and then to 2001-2010. We found that in both lymphoma and leukemia, the higher exposure category was associated with lower SIRs in both men and women. In terms of time trends, the SIRs in both lymphoma and leukemia showed increasing trends in both sexes, while exposure to arsenic in drinking water decreased over time. The arsenic level in drinking water was negatively associated with the incidences of lymphoma and leukemia in both men and women. This study supports the dual effects of arsenic on carcinogenesis, with a potential protective effect against hematologic malignancies.

Risk stratification and cost-effectiveness analysis of adult patients receiving extracorporeal membrane oxygenation.

RATIONALE, AIMS, AND OBJECTIVES: A more effective allocation of critical care resources is important as the cost of intensive care increases. A model has been developed to predict the probability of in-hospital death among patients who received extracorporeal membrane oxygenation (ECMO). Cost-effectiveness analyses (CEA) were performed regarding the relationship between hospitalization expenses and predicted survival outcomes. METHODS: Adult patients who received ECMO in a medical center in Taiwan (2005-2016) were included. A logistic regression model was applied to a spectrum of clinical measures obtained before and during ECMO institutions to identify the risk variables for in-hospital mortality. CEA were reported as a predictive risk in quintiles and defined as the cost of each quality-adjusted life-year (QALY). The distribution of the cost-effectiveness ratio (CER) was measured by the ellipse and acceptability curve methods. RESULTS: A total of 919 patients (659 males, mean age: 53.7 years) were enrolled. Ten variables emerged as significant predictors of in-hospital death. The area under the receiver operating characteristic curve was 0.75 (95% confidence interval: 0.72-0.79). In-hospital and total follow-up times were 40,366 and 660,205 person-days, respectively. The total in-hospital expense was $31,818,701 USD and the total effectiveness was 1687.3 QALY. For the lowest to the highest risk quintile, the mean mortality risks were 0.30, 0.48, 0.61, 0.75, and 0.88, and mean adjusted CER were $24,230, $43,042, $54,929, $84,973, and $149,095 per QALY, respectively. CONCLUSIONS: The efficient allocation of limited and costly resources is most important when one is forced to decide between groups of critically ill patients. The current analyses of ECMO outcomes should assist in identifying candidates with the greatest prospect for survival while avoiding futile treatments.

Risk factors for lymphatic and hematogenous metastasis after diagnosis of cutaneous Melanoma in Taiwan.

BACKGROUND: Risk factors of lymphatic and hematogenous metastasis in cutaneous melanoma remained unclear in Asian population. This study aimed to identify clinical and histopathological factors to predict metastatic pathways in cutaneous melanoma in Taiwan. METHODS: A total of 247 patients diagnosed as stage I and II melanoma, followed at National Taiwan University Hospital were included in this retrospective study from 1980 to 2020. Kaplan-Meier curves and Cox proportional hazards regression were utilized to identify risk factors. RESULTS: During a median follow-up of 143 months, 48 (19.4%) and 62 (25.1%) patients developed lymphatic and hematogenous metastasis respectively. In the univariate analysis, age> 70 years, greater Breslow thickness, ulceration, neurotropism, and NRAS mutation were significant risk factors for lymphatic metastasis in all subtypes of melanoma. Age >70 years, head and neck location, thickness, ulceration, higher mitotic rate, neurotropism, and NRAS mutation were significant predictors of hematogenous metastasis in all subtypes. In the multivariate analysis, greater thickness (HR for 2.0-4.0 mm, 4.5; p = .009 and HR for >4.0 mm, 5.7; p = .003) retained its significance as an independent risk factor for lymphatic metastasis in all subtypes of melanoma. Thickness (HR for >4.0 mm, 5.7; p < .001) and ulceration (HR, 2.5; p = .001) were independent risk factors for hematogenous metastasis. CONCLUSION: Risk factors of metastasis not only differ between lymphatic and hematogenous pathways, but also differ between ethnics and melanoma subtypes. Better understanding the behavior of cutaneous melanoma may help guide further treatments and follow-up plans.