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1.
J Phys Chem Lett ; 15(36): 9311-9318, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39235329

ABSTRACT

New perovskite materials of two-dimensional (2D) all-inorganic Ruddlesden-Popper (RP) perovskite Cs6Pb5I16 nanosheets were successfully obtained from the structural transformation of 2D PR-phase Cs7Pb6I19 nanosheets. The 2D RP-phase Cs6Pb5I16 perovskite nanosheets exhibited unique green emission with an emission wavelength of ∼500 nm. The crystal structure of the 2D RP-phase Cs6Pb5I16 perovskite nanosheets was determined by powder X-ray diffraction (XRD), high-resolution transmission electron microscopy, and atomic force microscopy. The time-dependent photoluminescence measurements and XRD spectra were used to observe the optical and structure transformations from 2D Cs7Pb6I19 (n = 6) to 2D Cs6Pb5I16 (n = 5) perovskites. The in situ XRD measurements confirmed that γ-phase CsPbI3 was released during the structural transformation. Moreover, temperature-dependent in situ XRD measurements were employed to examine the kinetic energy involved in the structural transformation from the n = 6 form to the n = 5 form. Specifically, an intermediate structure from n = 6 to n = 5 was also identified. Most importantly, 2D Cs6Pb5I16 (n = 5) was more structurally thermodynamically stable than 2D Cs7Pb6I19 (n = 6). This study provides an essential route for the discovery of new types of perovskite structures during structural transformation.

2.
Spine J ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39154948

ABSTRACT

BACKGROUND CONTEXT: Osteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated. PURPOSE: This study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment. STUDY DESIGN: Retrospective nationwide cohort study PATIENT SAMPLE: A total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures. OUTCOME MEASURES: The risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. METHODS: This is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their antiosteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. RESULTS: A total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16-2.32), 1.74 (95% CI, 1.25-2.42) and 1.53 (95% CI, 1.14-2.06). If osteoporotic fractures were divided into nonvertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54-1.88) for nonpersistent denosumab users, 1.64 (95% CI: 0.96-2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95-2.43) for nonpersistent bisphosphonate users. However, there was a significantly greater risk of nonvertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33-3.11), 1.80 (95% CI, 1.18-2.76) and 1.56 (95% CI, 1.06-2.27) for nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent users. Noteworthy, nonpersistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22-4.38). CONCLUSIONS: In terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or nonpersistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab.

3.
J Microbiol Immunol Infect ; 57(5): 739-748, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38816319

ABSTRACT

BACKGROUND: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations. METHODS: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected. RESULTS: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus. CONCLUSION: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.


Subject(s)
HIV Infections , Homosexuality, Male , Hypogonadism , Testosterone , Humans , Male , Taiwan/epidemiology , Adult , Hypogonadism/epidemiology , Hypogonadism/blood , Testosterone/blood , Prevalence , HIV Infections/complications , HIV Infections/epidemiology , Homosexuality, Male/statistics & numerical data , Middle Aged , Sex Hormone-Binding Globulin/analysis , Young Adult , Body Mass Index , Risk Factors
4.
Poult Sci ; 103(6): 103669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38603931

ABSTRACT

In the poultry industry, broiler and layer strains are genetically selected for different purposes (e.g., high meat-yield and high egg-production). Genetic selection for productivity can have unintended consequences on the behavioral repertoire of the birds, including aggression. Alongside the increasing societal concern regarding the welfare of animal in agriculture, the number of countries that are advocating the prohibition of using battery cages for laying hens has resulted in the transition and adoption of cage-free or free-range systems. Thus, both broiler and layer chickens are housed in large flocks rather than housed individually in cages. Housing birds in groups increases the opportunity for birds to engage in social behaviors, including aggression, that are used to establish social status. Aggressive interactions are associated with the risk of injury and the potential for a subordinate animal to have unmet needs (e.g., access to feed). The aim of this study was to characterize the relationships among aggressive behavior, neurobiology, and hormones during peck order establishment and social hierarchy stabilization of 2 divergently selected strains (meat- and egg-type chicken). Meat-type strains performed more male on male (P < 0.001), male on female (P < 0.0001), and female on female (P < 0.0001) non-reciprocal aggression behavior (NRA) than egg-type strains. Greater serum testosterone and estradiol concentrations in the weeks after the peck order establishment were observed in meat-type birds compared those in egg-type birds for both males and females (all P < 0.05). Greater (P < 0.05) cellular densities of androgen receptors, but not estrogen receptors, were observed in the hypothalamus of meat-type birds compared to egg-type birds. These findings suggest that greater sex hormone concentrations in the meat-type birds may be a consequence of genetic selection for rapid growth resulting in more sex hormones-induced aggressive behavior.


Subject(s)
Aggression , Chickens , Animals , Chickens/physiology , Chickens/genetics , Male , Female , Behavior, Animal/physiology , Gonadal Steroid Hormones/metabolism
5.
Sci Rep ; 14(1): 2849, 2024 02 03.
Article in English | MEDLINE | ID: mdl-38310128

ABSTRACT

Low physical activity has been associated with poor prognosis in hemodialysis (HD) patients. Interventions to maintain healthy lifestyle in this population are important to reduce mortality. This study aimed to evaluate the effectiveness of digital health interventions (DHIs) for improving the physical activity and health-related quality of life (HRQoL) in HD patients. The 24-week prospective study enrolled 31 clinically stable HD patients. All participants were assigned home exercises and provided with wearable devices. Dietary and exercise information was uploaded to a health management platform. Suggestions about diet and exercise were provided, and a social media group was created. Physical performance testing was performed at baseline and during weeks 4, 8, 12, 16 and 24. HRQoL and nutritional status were evaluated. A total of 25 participants completed the study. After the interventions, the daily step count increased 1658 steps. The 10-time-repeated sit-to-stand test reduced by 4.4 s, the sit-to-stand transfers in 60 s increased 12 repetitions, the distance of six-minute walk test (6MWT) increased by 55.4 m. The mental health components and burden of kidney disease of the Kidney Disease Quality of Life survey, and subjective global assessment (SGA) scores improved. By Spearman correlation, the monthly step count correlated positively with 6MWT and SGA. DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients. The results outline a new model to promote healthy lifestyle behaviors in HD patients.


Subject(s)
Kidney Diseases , Quality of Life , Humans , Pilot Projects , Prospective Studies , Digital Health , Renal Dialysis/methods , Healthy Lifestyle
6.
J Formos Med Assoc ; 123(9): 968-974, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38307800

ABSTRACT

BACKGROUND: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. METHODS: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. RESULTS: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432-5p and miRNA-382-3p were upregulated in patients with abnormal SSS. CONCLUSION: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.


Subject(s)
Coronary Angiography , Coronary Artery Disease , Exosomes , MicroRNAs , Myocardial Perfusion Imaging , Humans , Female , Male , Aged , Middle Aged , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/physiopathology , MicroRNAs/blood , Multivariate Analysis
7.
Clin Pharmacol Ther ; 115(1): 147-157, 2024 01.
Article in English | MEDLINE | ID: mdl-37926942

ABSTRACT

Biological plausibility suggests that fluoroquinolones may lead to mitral valve regurgitation or aortic valve regurgitation (MR/AR) through a collagen degradation pathway. However, available real-world studies were limited and yielded inconsistent findings. We estimated the risk of MR/AR associated with fluoroquinolones compared with other antibiotics with similar indications in a population-based cohort study. We identified adult patients who initiated fluoroquinolones or comparison antibiotics from the nationwide Taiwanese claims database. Patients were followed for up to 60 days after cohort entry. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of MR/AR comparing fluoroquinolones to comparison antibiotics after 1:1 propensity score (PS) matching. All analyses were conducted by type of fluoroquinolone (fluoroquinolones as a class, respiratory fluoroquinolones, and non-respiratory fluoroquinolones) and comparison antibiotic (amoxicillin/clavulanate or ampicillin/sulbactam, extended-spectrum cephalosporins). Among 6,649,284 eligible patients, the crude incidence rates of MR/AR ranged from 1.44 to 4.99 per 1,000 person-years across different types of fluoroquinolones and comparison antibiotics. However, fluoroquinolone use was not associated with an increased risk in each pairwise PS-matched comparison. HRs were 1.00 (95% CI, 0.89-1.11) for fluoroquinolones as a class, 0.96 (95% CI, 0.83-1.12) for respiratory fluoroquinolones, and 0.87 (95% CI, 0.75-1.01) for non-respiratory fluoroquinolones, compared with amoxicillin/clavulanate or ampicillin/sulbactam. Results were similar when fluoroquinolones were compared with extended-spectrum cephalosporins (HRs of 0.96, 95% CI, 0.82-1.12, HR, 1.05, 95% CI, 0.86-1.28, and HR, 0.88, 95% CI, 0.75-1.03, respectively). This large-scale cohort study did not find a higher risk of MR/AR with different types of fluoroquinolones in the adult population.


Subject(s)
Aortic Valve , Fluoroquinolones , Adult , Humans , Fluoroquinolones/adverse effects , Cohort Studies , Sulbactam , Anti-Bacterial Agents/adverse effects , Amoxicillin-Potassium Clavulanate Combination , Ampicillin , Cephalosporins
8.
Eur J Med Res ; 28(1): 347, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37715216

ABSTRACT

BACKGROUND: It is common to support cardiovascular function in critically ill patients with extracorporeal membrane oxygenation (ECMO). The purpose of this study was to identify patients receiving ECMO with a considerable risk of dying in hospital using machine learning algorithms. METHODS: A total of 1342 adult patients on ECMO support were randomly assigned to the training and test groups. The discriminatory power (DP) for predicting in-hospital mortality was tested using both random forest (RF) and logistic regression (LR) algorithms. RESULTS: Urine output on the first day of ECMO implantation was found to be one of the most predictive features that were related to in-hospital death in both RF and LR models. For those with oliguria, the hazard ratio for 1 year mortality was 1.445 (p < 0.001, 95% CI 1.265-1.650). CONCLUSIONS: Oliguria within the first 24 h was deemed especially significant in differentiating in-hospital death and 1 year mortality.


Subject(s)
Extracorporeal Membrane Oxygenation , Random Forest , Adult , Humans , Hospital Mortality , Oliguria , Algorithms
9.
J Formos Med Assoc ; 122 Suppl 1: S92-S100, 2023.
Article in English | MEDLINE | ID: mdl-37574339

ABSTRACT

BACKGROUND: Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). RESULTS: There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02-1.13), p = 0.0114 for those ages 70-79 years old; HR = 1.11 (1.06-1.17), p < 0.0001 for those ages ≥80 years) and mortality (HR = 1.18 (1.14-1.22), p < 0.0001 for those ages 70-79; HR = 1.20 (1.16-1.23), p < 0.0001) within 3 years post incident fracture; meanwhile, consuming fewer medical resources in the national insurance healthcare system. (Increment cost = -16011.2 NTD, p = 0.0248 for those ages 70-79; Increment cost = -17257.9 NTD, p = 0.0032 for those ages ≥80 years) CONCLUSION: Overall, under Taiwan's national health insurance, the use of AOMs is cost-saving, especially in the population aged ≥70 years. The finding of this research was valuable for policymakers in considering healthcare policy promotion and resource allocation in the future.

10.
J Formos Med Assoc ; 122 Suppl 1: S55-S64, 2023.
Article in English | MEDLINE | ID: mdl-37302970

ABSTRACT

BACKGROUND: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. METHODS: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. RESULTS: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. CONCLUSION: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.


Subject(s)
Bone Density Conservation Agents , Osteoporosis , Humans , Bone Density Conservation Agents/therapeutic use , Bone Density Conservation Agents/adverse effects , Alendronate/therapeutic use , Cohort Studies , Denosumab/therapeutic use , Zoledronic Acid/therapeutic use , Taiwan , Motivation , Medication Adherence , Osteoporosis/drug therapy , Retrospective Studies
11.
J Formos Med Assoc ; 122 Suppl 1: S36-S44, 2023.
Article in English | MEDLINE | ID: mdl-37280138

ABSTRACT

BACKGROUND: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. METHODS: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies. RESULTS: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018. CONCLUSION: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number.


Subject(s)
Bone Density Conservation Agents , Fractures, Bone , Osteoporosis , Osteoporotic Fractures , Male , Humans , Female , Aged , Bone Density Conservation Agents/therapeutic use , Taiwan , Osteoporosis/drug therapy , Fractures, Bone/drug therapy , Alendronate/therapeutic use , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control
12.
J Formos Med Assoc ; 122 Suppl 1: S45-S54, 2023.
Article in English | MEDLINE | ID: mdl-37271714

ABSTRACT

BACKGROUND: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. METHODS: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. RESULTS: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018. CONCLUSION: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas.


Subject(s)
Bone Density Conservation Agents , Osteoporosis , Humans , Taiwan , Urbanization , Osteoporosis/drug therapy , Alendronate/therapeutic use , Ibandronic Acid/therapeutic use , Bone Density Conservation Agents/therapeutic use
13.
J Formos Med Assoc ; 122 Suppl 1: S21-S35, 2023.
Article in English | MEDLINE | ID: mdl-37208247

ABSTRACT

BACKGROUND: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. METHODS: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). RESULTS: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%-2.91% and 2.08%-1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. CONCLUSION: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

14.
J Biomed Sci ; 30(1): 13, 2023 Feb 19.
Article in English | MEDLINE | ID: mdl-36803854

ABSTRACT

BACKGROUND: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. METHODS: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. RESULTS: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. CONCLUSIONS: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.


Subject(s)
Carrier Proteins , Hyperkalemia , Hypertension , Hypoaldosteronism , Animals , Humans , Mice , Aldosterone , Aluminum Oxide , Blood Pressure , Genome-Wide Association Study , Homeostasis , Hyperkalemia/complications , Hypoaldosteronism/complications , Potassium , Renin/genetics , Carrier Proteins/genetics , Carrier Proteins/physiology
15.
Clin Gastroenterol Hepatol ; 21(2): 424-434.e5, 2023 02.
Article in English | MEDLINE | ID: mdl-35131346

ABSTRACT

BACKGROUND & AIMS: Data regarding the long-term evolution of estimated glomerular filtration rate (eGFR) in patients receiving antiviral treatment for hepatitis C virus are limited. METHODS: A total of 1987 patients with eGFR ≥15 mL/min/1.73m2 who received interferon or direct-acting antiviral treatment were prospectively enrolled in this cohort study. The eGFR was assessed biannually by the Chronic Kidney Disease Epidemiology Collaboration equation from the time point of sustained virologic response (SVR12). Multivariate generalized estimated equation was used to assess the association between the factors of interest and evolution of eGFR following antiviral treatment. Multivariate Cox regression analysis was used to assess the relative risk of end-stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m2. RESULTS: Patients who achieved SVR12 (adjusted slope coefficient difference: 2.36 mL/min/1.73 m2/year; 95% confidence interval [CI], 1.50 to 3.32; P < .001) were associated with eGFR improvement, compared with those who did not achieve SVR12. Among patients who achieved SVR12, the eGFR evolution was comparable (adjusted slope coefficient difference: 0.31 mL/min/1.73m2/year; 95% CI, -0.34 to 0.96; P = .35) in those treated with interferon or direct-acting antiviral. The incidence rates of ESRD in patients who achieved and did not achieve SVR12 were 0.06 per 100 person-years and 0.37 per 100 person-years. Patients who achieved SVR12 were associated with a lower risk of ESRD (adjusted hazard ratio, 0.24; 95% CI, 0.05-0.68; P = .021). CONCLUSIONS: The long-term eGFR evolution and risk of ESRD are significantly improved in patients who achieve SVR12 with anti- hepatitis C virus treatment.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Kidney Failure, Chronic , Humans , Antiviral Agents/therapeutic use , Hepacivirus , Glomerular Filtration Rate/physiology , Cohort Studies , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C/complications , Hepatitis C/drug therapy , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/complications , Interferons/therapeutic use
16.
Front Pharmacol ; 13: 869804, 2022.
Article in English | MEDLINE | ID: mdl-36176438

ABSTRACT

Background: Both sodium glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have cardiovascular protective effects in patients with type 2 diabetes mellitus. However, the comparative risk of GLP-1RA versus SGLT-2i for major adverse limb events remains unknown. Materials and methods: We studied a nationwide cohort involving 123,048 diabetes patients 20-100 years of age who initiated a SGLT-2i or GLP-1RA during 2012 and 2017. The patients in the two groups were matched by propensity score (PS), and incidence rates for hospitalization for major adverse limb events, critical limb ischemia (CLI) and lower extremity amputation (LEA), were assessed. Cox proportional hazards regression was applied to estimate hazard ratios (HRs) between patients receiving SGLT-2i as compared with GLP-1RA. The modification effects of age, a history of established cardiovascular disease, and chronic kidney disease were examined. In addition, use of dipeptidyl peptidase-4 inhibitor (DPP-4i) was chosen as a second active comparator. Results: After PS-matching, a total of 13,378 SGLT-2i and 13,378 GLP-1RA initiators were identified. Use of SGLT-2i was not associated with an increased risk for hospitalization for CLI and LEA, either compared with GLP-1RA (HR, 1.13; 95% CI, 0.77-1.65 and 1.27; 95% CI, 0.63-2.55, respectively) or compared with DPP-4i use (HR, 1.06; 95% CI, 0.75-1.50 and HR, 0.80; 95% CI, 0.42-1.53, respectively). Although the study was underpowered to explore potential effect modification, a trend of higher risks for LEA was noted among SGLT-2i users with cardiovascular disease as compared with either GLP-1RA or DPP-4i. Conclusion: Use of SGLT-2i was not associated with higher risks for hospitalization for CLI and LEA as compared with reference drugs. Further large-scale studies are needed for a precise risk estimation.

17.
Mater Horiz ; 9(9): 2433-2442, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-35848594

ABSTRACT

Two-dimensional (2D) all-inorganic Ruddlesden-Popper (RP) perovskite Cs7Pb6I19 nanosheets (NSs) were successfully developed for the first time by employing a structural recrystallization process with additional passivation of small organic sulfide molecules. The structure of Cs7Pb6I19 NSs is confirmed by powder X-ray diffraction measurements, atomically-resolved STEM measurements and atomic force microscopy (AFM) studies. Cs7Pb6I19 NSs with a specific n value of 6 exhibits unique absorption and emission spectra with intense excitons at 560 nm due to quantum confinement effects in 2D perovskite slabs. The formation mechanisms of 2D Cs7Pb6I19 NSs and 3D γ-CsPbI3 phases were investigated by in situ photoluminescence (PL) spectroscopy and the activation energies of their formation reactions were calculated to be 151 kJ mol-1 and 95.3 kJ mol-1, respectively. The phase stability of 2D Cs7Pb6I19 NSs can be maintained at temperatures below 14 °C for more than 4 weeks. The overall results indicate that 2D Cs7Pb6I19 NSs demonstrate unique optical properties and structural stability compared with other 3D perovskite materials. We have opened a new path to the future discovery of 2D perovskite structures with metastable phases by using this recrystallization method and the assistance of sulfur-derived organic molecules.

18.
Chin J Physiol ; 65(3): 109-116, 2022.
Article in English | MEDLINE | ID: mdl-35775529

ABSTRACT

Spasticity measured using clinical scales, such as the modified Ashworth scale (MAS), may not sufficiently evaluate the effectiveness of therapeutic interventions and predict prognosis. This study aimed to compare changes in H-reflex excitability in the spastic and unimpaired upper and lower limbs of patients with acute and chronic stroke. We also investigated the relationship between the degree of spasticity as assessed by the MAS and motor neuron pool excitability with by analyzing H-reflex excitability. Sixty adult patients with a first-ever stroke were recruited for this study. MAS scores were recorded in the post-stroke upper and lower limb muscles. H-reflexes and M-responses of the bilateral flexor carpi radialis and soleus were tested by stimulating the median and tibial nerves. The results showed that both the ratio of the maximal size of the H-reflex (Hmax) to the maximal size of the M-response (Mmax) and the ratio of the developmental slope of H-reflex (Hslp) to that of the M-responses (Mslp) were significantly higher on the spastic side than on the unimpaired side for the upper and lower limbs. In contrast, the ratio of the threshold of the H-reflex (Hth) to the threshold of the M-response (Mth) only showed significant differences between the two sides in the upper limbs. The Hslp/Mslp paretic/non-paretic ratio was increased in patients with MAS scores of 2 or 3 compared to MAS scores of 1 for both the upper and lower limbs, whereas the Hmax/Mmax paretic/non-paretic ratio showed significant differences between MAS scores of 2 or 3 and 1 only in the upper limbs. Moreover, in either the spastic or unimpaired sides, there were no significant differences in any of the three motoneuron pool excitability parameters, Hmax/Mmax, Hslp/Mslp, and Hth/Mth, between the shorter chronicity (time post-stroke ≤6 months) and longer chronicity groups (time post-stroke >6 months) for both the upper and lower limbs. These results suggest that Hslp/Mslp could be a potential neurophysiological indicator for evaluating the degree of spasticity in both the upper and lower limbs of patients with hemiplegia. The MAS and Hslp/Mslp characterize clinical and neurophysiologic spasticity, respectively, and could be used as an integrated approach to evaluate and follow up post-stroke spasticity.


Subject(s)
Muscle Spasticity , Stroke , Adult , Humans , Motor Neurons , Muscle Spasticity/diagnosis , Muscle Spasticity/etiology , Stroke/complications , Upper Extremity
19.
Nanomaterials (Basel) ; 12(11)2022 May 26.
Article in English | MEDLINE | ID: mdl-35683671

ABSTRACT

Various types of 2D organic-inorganic perovskite solar cells have been developed and investigated due to better electron transport behavior and environmental stability. Controlling the formation of phases in the 2D perovskite films has been considered to play an important role in influencing the stability of perovskite materials and their performance in optoelectronic applications. In this work, Lewis base urea was used as an effective additive for the formation of 2D Ruddlesden-Popper (RP) perovskite (BA)2(MA)n-1PbnI3n+1 thin film with mixed phases (n = 2~4). The detailed structural morphology of the 2D perovskite thin film was investigated by in situ X-ray diffraction (XRD), grazing-incidence small-angle X-ray scattering (GISAXS) and photoluminescence mapping. The results indicated that the urea additive could facilitate the formation of 2D RP perovskite thin film with larger grain size and high crystallinity. The 2D RP perovskite thin films for solar cells exhibited a power conversion efficiency (PCE) of 7.9% under AM 1.5G illumination at 100 mW/cm2.

20.
Clin Transplant ; 36(11): e14746, 2022 11.
Article in English | MEDLINE | ID: mdl-35751454

ABSTRACT

BACKGROUND: Mechanical circulatory support (MCS) has been widely utilized in critically ill cardiac transplant candidates. Few studies have investigated the impact of duration of MCS before heart transplantation (HTx) on long-term patient survival. METHODS: A retrospective HTx database was reviewed between 2009 and 2019. Patients who did not or did undergo MCS before HTx were categorized into two groups: (1) A (did not) and (2) B (did), respectively. A receiver operating characteristic (ROC) curve was plotted to assess the cutoff level of MCS duration before HTx in evaluating 5-year survival. RESULT: A total of 270 HTx patients (group A: 120, group B: 150) were analyzed. Group B patients had a higher percentage of blood type O, a higher incidence of resuscitation, a shorter listing duration, and a higher likelihood of having United Network for Organ Sharing (UNOS) 1A status than group A. The ROC curve revealed 24 days as a good cut-off level for determining the best MCS before HTx timing. Group B was categorized into two subgroups: (1) B1 (MCS < 24 days, n = 65) and (2) B2 (MCS > 24 days, n = 85). B2 had a higher incidence of cardiopulmonary resuscitation (CPR), hemodialysis, longer waiting time after MCS, and better ventricular assist device implantation than B1. However, the survival curves showed that B1 outcomes were significantly worse than in groups A and B2. Groups A and B2 had similar survival curves without an increased incidence of infection. CONCLUSION: The preliminary data demonstrated that a longer duration of MCS may be associated with better outcomes than urgent HTx.


Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Humans , Retrospective Studies , Treatment Outcome , Time Factors , Heart Failure/surgery
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