Analyzing genomic variation in cultivated pumpkins and identification of candidate genes controlling seed traits.

Pumpkins are important vegetable crops widely grown worldwide, and seeds are considered a popular nutraceutical food and an excellent source of protein, oil, and vitamins. Seed size is one of the most important targets for commercial breeding in Cucurbita species; studies have shown that pumpkin seed size variation has a similar trend with fruit size, shape, and seed yield. However, few studies have been conducted to identify genetic loci controlling seed-related traits in cultivated pumpkins. This study analyzed the genomic characteristics of pumpkin breeding materials of 321 Cucurbita accessions collected worldwide, including Cucurbita moschata, Cucurbita maxima, and Cucurbita pepo, using extensive single nucleotide polymorphisms obtained from the genotyping-by-sequencing method, significant genetic variations were identified within and between Cucurbita species. Four major cultivar fruit types were further revealed in C. moschata species, and significant differentiation patterns were detected in several chromosomal regions. A total of 15 significant loci associated with pumpkin seed traits were mapped through a genome-wide association approach; 32 genes previously reported to be associated with seed size regulation in Arabidopsis and Oryza sativa were located in the intervals defined by linkage disequilibrium. Through this study, we gained a deep understanding of the genomic variation distribution across Cucurbita species. The available genetic resources and the associated genetic contents could be used in commercial pumpkin breeding and will facilitate molecular marker-assisted selection in pumpkin seed trait improvement.

The effect of joint involvement of nurse and physician in hospice care on terminal cancer patients on do-not-resuscitate orders signed by surrogates.

OBJECTIVES: Patients with terminal cancer often experience physical and mental distress. Signing a do-not-resuscitate order (DNR) is crucial to protect against invalid treatment. This study aims to explore the effect of hospice shared care intervention by medical staff on the completion of a DNR-S (DNR order signed by surrogates) for patients with terminal cancer. METHOD: The cross-sectional study in this research involved secondary analysis of data from the 2011-2015 clinical cancer case management database of a medical center in central Taiwan. Those with a DNR order signed by patients (DNR-P) or DNR-S before the hospice shared care consultation were excluded from this study; a total of 1,306 patients with terminal cancer were selected. RESULTS: This study demonstrated that the percentage of DNR-S after consultation involving both nurse and physician was 75.4%. With other variables controlled, the number of DNR-Ss after consultation with a nurse was significantly lower [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.42-0.75] and that of DNR-Ss after consultation involving both nurse and physician was significantly higher (OR = 1.35, 95% CI = 1.01-1.79), than that of DNR-Ss after consultation with only the physician. SIGNIFICANCE OF RESULTS: Joint involvement of the nurse and physician in hospice care provides sufficient information to patients and family with terminal cancer about their condition and enhances doctor-patient communication. This effectively assists patients with terminal cancer and their family members in making the major decision of signing a DNR, alleviates the concerns of patients and family members about signing a DNR, and reduces terminal cancer patients' pain at the end of life to ensure that they die in peace and dignity.

Correlational Study of Emotional Stress, Pain, and the Presence of Inpatient Companions for Cancer Inpatients during the COVID-19 Pandemic.

The outbreak of COVID-19 poses an immense global threat. Visitors to hospitalized patients during a pandemic might themselves be carriers, and so hospitals strictly control patients and inpatient companions. However, it is not easy for cancer patients to adjust the times of their medical treatment or to suspend treatment, and the impact of the pandemic on cancer inpatients and inpatient companions is relatively high. The objectives for this investigation are to study the correlations among emotional stress, pain, and the presence of inpatient companions in cancer patients during the COVID-19 pandemic. This study was a retrospective descriptive study. The participants were cancer inpatients and inpatient companions in a medical center in Taiwan. The data for this study were extracted from cross-platform structured and normalized electronic medical record databases. Microsoft Excel 2016 and SPSS version 22.0 were used for analysis of the data. In all, 75.15% of the cancer inpatients were accompanied by family, and the number of hospitalization days were 7.87 ± 10.77 days, decreasing year by year, with statistical significance of p < 0.001. The daily nursing hours were 12.94 ± 10.76, and the nursing hours decreased year by year, p < 0.001. There was no significant difference in gender among those who accompanied the patients, but there were statistical differences in the length of hospitalization, nursing hours, and pain scores between those with and without inpatient companions, with p < 0.001. The inpatient companions were mostly family members (78%). The findings of this study on cancer patient care and inpatient companions should serve as an important basis for the transformation and reform of the inpatient companion culture and for epidemic prevention care in hospitals.

Prevention of needle-stick injury among nurses in an acute ward of a hospital: a best practice implementation project.

OBJECTIVES: This evidence implementation project aimed to identify barriers leading to needle-stick injuries (NSIs) and to develop implementation strategies to prevent NSIs in the acute ward of a hospital in central Taiwan. INTRODUCTION: The incidence rate of NSIs was 5.6% in the acute ward of a hospital in Taiwan. NSIs commonly occur during the drawing of blood, intravenous insertion, needle recapping, or performing any procedure involving sharp medical devices. NSIs are critical occupational risks among healthcare workers, possibly leading to transmission of infectious diseases, especially blood-borne viruses, such as HIV, hepatitis B, and hepatitis C. METHODS: A clinical audit was undertaken using the JBI Practical Application of Clinical Evidence System (PACES) and the Getting Research into Practice (GRiP) approach. Five audit criteria that represented best practice recommendations for prevention of NSIs were used. Baseline data were collected from 177 nurses in five acute wards, followed by the implementation of multiple strategies during a 20-week period of the project. Both baseline and postimplementation audits were undertaken to determine changes in practice. RESULTS: According to the pre-audit concerning the use of safety-engineered injection devices and safe use and disposal of needles, there was 14-15% compliance, which indicated poor compliance with current best-practice criteria. Following the project implementation, the nursing staff were educated about the well tolerated use and disposal of sharps and the improved compliance rate ranged from 40 to 96.6%, with safety needle use increasing from 16 to 95.5%, safety needle operation procedure awareness increasing from 14 to 96%, needles not recapped after use increasing from 47 to 85%, and placing used needles in the sharps collection box increasing from 75 to 80%. CONCLUSION: This article suggests that standardized puncture prevention education and training enhanced nurses' awareness in the acute ward.

Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study.

PURPOSE: Pathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC. METHODS: Patients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals. RESULTS: There were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan-Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1-2) or advanced T stage (T3-4). CONCLUSIONS: Pathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.

Comparison of Two Quantitative PCR-Based Assays for Detection of Minimal Residual Disease in B-Precursor Acute Lymphoblastic Leukemia Harboring Three Major Fusion Transcripts.

Two quantitative PCR (qPCR)-based methods, for clonal immunoglobulin or T-cell receptor gene (Ig/TCR) rearrangements and for fusion transcripts, are widely used for the measurement of minimal residual disease (MRD) in patients with B-precursor acute lymphoblastic leukemia (ALL). MRD of bone marrow samples from 165 patients carrying the three major fusion transcripts, including 74 BCR-ABL1, 54 ETV6-RUNX1, and 37 TCF3-PBX1, was analyzed by using the two qPCR-based methods. The correlation coefficient of both methods was good for TCF3-PBX1 (R2 = 0.8088) and BCR-ABL1 (R2 = 0.8094) ALL and moderate for ETV6-RUNX1 (R2 = 0.5972). The concordance was perfect for TCF3-PBX1 ALL (97.2%), substantially concordant for ETV6-RUNX1 ALL (87.1%), and only moderate for BCR-ABL1 ALL (70.6%). The discordant MRD, positive for only one method with a difference greater than one log, was found in 4 of 93 samples (4.3%) with ETV6-RUNX1, 31 of 245 samples (12.7%) with BCR-ABL1, and none of TCF3-PBX1 ALL. None of the eight non-transplanted patients with BCR-ABL1-MRD (+)/Ig/TCR-MRD (-) with a median follow-up time of 73.5 months had hematologic relapses. Our study showed an excellent MRD concordance between the two qPCR-based methods in TCF3-PBX1 ALL, whereas qPCR for Ig/TCR is more reliable in BCR-ABL1 ALL.

Antibody Watch: Text mining antibody specificity from the literature.

Antibodies are widely used reagents to test for expression of proteins and other antigens. However, they might not always reliably produce results when they do not specifically bind to the target proteins that their providers designed them for, leading to unreliable research results. While many proposals have been developed to deal with the problem of antibody specificity, it is still challenging to cover the millions of antibodies that are available to researchers. In this study, we investigate the feasibility of automatically generating alerts to users of problematic antibodies by extracting statements about antibody specificity reported in the literature. The extracted alerts can be used to construct an "Antibody Watch" knowledge base containing supporting statements of problematic antibodies. We developed a deep neural network system and tested its performance with a corpus of more than two thousand articles that reported uses of antibodies. We divided the problem into two tasks. Given an input article, the first task is to identify snippets about antibody specificity and classify if the snippets report that any antibody exhibits non-specificity, and thus is problematic. The second task is to link each of these snippets to one or more antibodies mentioned in the snippet. The experimental evaluation shows that our system can accurately perform the classification task with 0.925 weighted F1-score, linking with 0.962 accuracy, and 0.914 weighted F1 when combined to complete the joint task. We leveraged Research Resource Identifiers (RRID) to precisely identify antibodies linked to the extracted specificity snippets. The result shows that it is feasible to construct a reliable knowledge base about problematic antibodies by text mining.

Early Screening of Risk for Multidrug-Resistant Organisms in the Emergency Department in Patients With Pneumonia and Early Septic Shock: Single-Center, Retrospective Cohort Study.

OBJECTIVES: Pneumonia is the fourth leading cause of death globally, with rapid progression during sepsis. Multidrug-resistant organisms (MDROs) are becoming more common with some healthcare-associated pneumonia events. Early detection of MDRO risk improves the outcomes; however, MDROs risk in pneumonia with sepsis is unknown. This study investigated the disease outcomes of pneumonia with septic shock in patients admitted in the emergency department (ED) intensive care unit (ICU), a population with a high prevalence of MDROs, after early screening of MDROs risk. METHODS: In this retrospective cohort study, patients with pneumonia and early septic shock (n = 533) admitted to the ED at the Taipei Tzu Chi Hospital from 2013 to 2019 were selected. The study population was divided into four subgroups after the MDROs risk and screening procedure were completed within 1 or 6 h of admission. ICU mortality and multidrug antibiotic therapy were compared. RESULTS: The high-risk MDROs groups had higher percentage of P aeruginosa than the low-risk group. Furthermore, the appropriate ED first antibiotics were higher in the 1-h subgroup than in the 6-h subgroup of the high-risk MDROs group. In multivariate analysis, the 6-h high-risk MDROs group had an adjusted odds ratio of 7.191 (95% CI: 2.911-17.767, P < 0.001) and 2.917 (95% CI: 1.456-5.847, P = 0.003) for ICU mortality and multidrug therapy in the ICU, respectively, after adjusting for other confounding factors. CONCLUSIONS: MDRO screening within 1 h is recommended following admission of patients with pneumonia and early septic shock in the ED, especially in areas with a high prevalence of MDROs.

Pain prevalence in hospitalized patients at a tertiary academic medical center: Exploring severe persistent pain.

OBJECTIVE: The pain prevalence of inpatients is not a well-studied medical issue in Asia. We have aimed to evaluate pain prevalence and characterize those patients who have suffered from severe, persistent pain. METHODS: We investigated pain prevalence using a quota sampling from 19 general wards during the year 2018. Using a structured questionnaire, eight interviewers visited patients at an age ≥ 20 years, and who had been staying in general wards for ≥ 3 days. Those patients were excluded if they were unable to respond to the interview questions. If they reported pain during hospitalization, the maximum pain level and the duration of pain suffered in the past 24 hours were assessed. Care-related pain was also surveyed. RESULTS: A total of 1,034 patients (M/F, 537/497) completed the survey. Amongst them, 719 patients (69.5%) experienced pain, with moderate and severe pain levels being 27.3% and 43%, respectively. Surgery was considered as it related to pain, including significantly severe pain. The top 3 care-related pain causes were needle pain, wound dressing, and change in position/chest percussion. Change in position/chest percussion and rehabilitation were associated with severe, persistent pain. CONCLUSIONS: Pain is common in approximately 70% of inpatients, with surgery being associated with severe pain. Mobilization and rehabilitation may lead to severe, persistent pain. The periodic study of pain prevalence is essential in order to provide precise pain management.

Changes in Glucose Metabolism after Adrenalectomy or Treatment with a Mineralocorticoid Receptor Antagonist for Primary Aldosteronism.

BACKGROUND: Data on the effects of excess aldosterone on glucose metabolism are inconsistent. This study compared the changes in glucose metabolism in patients with primary aldosteronism (PA) after adrenalectomy or treatment with a mineralocorticoid receptor antagonist (MRA). METHODS: Overall, 241 patients were enrolled; 153 underwent adrenalectomy and 88 received an MRA. Fasting glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and homeostatic model assessment of ß-cell function (HOMA-ß) were compared between the treatment groups after 1 year. Plasma aldosterone concentration (PAC) and factors determining HOMA-IR and PAC were evaluated. RESULTS: No baseline differences were observed between the groups. Fasting insulin, HOMA-IR, and HOMA-ß increased in both groups and there were no significant differences in fasting glucose following treatment. Multiple regression analysis showed associations between PAC and HOMA-IR (ß=0.172, P=0.017) after treatment. Treatment with spironolactone was the only risk factor associated with PAC >30 ng/dL (odds ratio, 5.2; 95% confidence interval [CI], 2.7 to 10; P<0.001) and conferred a 2.48-fold risk of insulin resistance after 1 year compared with surgery (95% CI, 1.3 to 4.8; P=0.007). CONCLUSION: Spironolactone treatment might increase insulin resistance in patients with PA. This strengthened the current recommendation that adrenalectomy is the preferred strategy for patient with positive lateralization test. Achieving a post-treatment PAC of <30 ng/dL for improved insulin sensitivity may be appropriate.

Differential diagnosis of atypical encephalopathy in critical care: a case report.

BACKGROUND: A lower level of consciousness is a common presentation in critical care, with many different causes and contributory factors, of which more than one may be present concurrently. CASE PRESENTATION: We described a woman with poorly controlled diabetes and steroid-dependent asthma who presented in a deep coma. She was found to have Streptococcus intermedius bacteremia and pyogenic ventriculitis that originated from right middle lobe pneumonia. Also, multiple small parenchymal lesions were observed on brain magnetic resonance imaging and increased protein concentration was noted in cerebral spinal fluid. Initially, her coma was thought to be due to diabetic ketoacidosis and septic encephalopathy. However, her lowered level of consciousness was disproportionate to either diabetic ketoacidosis or septic encephalopathy, and her clinical course was not as expected for these two conditions. Treatment with antibiotic, corticosteroid and antihelminthic drugs was administered resulting in improving consciousness. The Streptococcus intermedius pneumonia progressed to form a large cavity that needed an early surgical lobectomy and resulted in the unexpected diagnosis of chronic cavitary pulmonary aspergillosus. CONCLUSIONS: In critical care, a lowered level of consciousness may have many etiologies, and critical care clinicians should be familiar with the signs and symptoms of all possible causes to enable prompt diagnosis and appropriate treatment.

The Needs and Utilization of Long-Term Care Service Resources by Dementia Family Caregivers and the Affecting Factors.

This study was to evaluate the utilization of long-term care service resources by caregivers of patients with dementia (PWD) and to determine affecting factors. In this cross-sectional study, a total of 100 dyads were enrolled and caregivers responded to the questionnaires. We found 40% of caregivers not using any care resources. Between those caregivers using and not-using care resources, we found differences (p < 0.05) in their health status and living conditions; the difference (p < 0.05) was also found in patients' behavior and psychological symptoms of dementia (BPSD). The frequency of BPSD (OR = 1.045, p = 0.016, 95% CI = 1.001-1.083) and the living conditions (OR = 3.519, p = 0.007, 95% CI = 1.414-8.759) were related to their use of care resources. Particular BPSDs, such as anxiety or restlessness, throwaway food, aggressive behavior, tearing of clothes, and sexual harassment of patients were related to the caregivers' use of care resources (p < 0.01). Health professionals have to evaluate the patients' BPSD and identify the caregivers' essential needs. Individualized medical care and BPSD-related care resources should be provided for patients and caregivers for taking off their care burden and improving patient care.

Cultural Impact on the Intention to Use Nursing Information Systems of Nurses in Taiwan and China: Survey and Analysis.

BACKGROUND: Nursing workforce shortage has emerged as a global problem. Foreign nurse importation is a popular strategy to address the shortage. The interactions between nursing staff on either side of the Taiwan Strait continue to increase. Since both nurses in Taiwan and nurses in China have adopted nursing information systems to improve health care processes and quality, it is necessary to investigate factors influencing nursing information system usage in nursing practice. OBJECTIVE: This study examined the effects of cultural and other related factors on nurses' intentions to use nursing information systems. The findings were expected to serve as an empirical base for further benchmarking and management of cross-strait nurses. METHODS: This survey was conducted in two case hospitals (one in Taiwan and one in China). A total of 880 questionnaires were distributed (n=440 in each hospital). RESULTS: The results showed effort expectancy had a significant effect on the intention to use nursing information systems of nurses in China (P=.003) but not nurses in Taiwan (P=.16). CONCLUSIONS: Findings suggest nursing managers should adopt different strategies to motivate cross-strait nurses to use nursing information systems. Promoting effort expectancy is more likely to motivate nurses in China than in Taiwan. This discrepancy is probably due to the less hierarchical and more feminine society in Taiwan.

Occupational, Transport, Leisure-Time, and Overall Sedentary Behaviors and Their Associations with the Risk of Cardiovascular Disease among High-Tech Company Employees.

This study examined the associations of overall and domain-specific (i.e., occupational, transport, and leisure-time) sedentary behaviors with cardiovascular disease (CVD) risk factors among high-tech company employees in Taiwan. A total of 363 participants employed at high-tech companies (mean age ± standard deviation: 37.4 ± 7.2 years) completed a questionnaire administered by email regarding their overall, occupational, transport, and leisure-time sedentary behaviors. Self-reported data of height and weight, blood pressure, blood sugar, and total cholesterol levels were also collected in 2018. An adjusted binary logistic regression model was employed in the analysis. After adjusting for sociodemographic variables, high-tech company employees who used a computer (or Internet) for more than 2 h per day during their leisure time were more likely to have CVD risk factors (odds ratio: 1.80; 95% confidence interval: 1.08-3.00). No significant associations with CVD risk factors were detected for total sedentary time, occupational sitting, television viewing time, and transport-related sitting. Despite the nature of cross-sectional design in this study, our findings may have considerable implications for intervention designers and policymakers of Taiwan. Developing effective strategies for limiting leisure-time computer use should be considered for the prevention of CVD among high-tech company employees.

Adrenalectomy Completely Cured Hypertension in Patients With Familial Hyperaldosteronism Type I Who Had Somatic KCNJ5 Mutation.

CONTEXT: Familial hyperaldosteronism type I (FH-I) or glucocorticoid-remediable aldosteronism (GRA) is caused by unequal crossing over of the steroid 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. Somatic KCNJ5 mutations have not been reported in patients with GRA; therefore, the appropriate treatment and prognosis of such concurrent cases remain unknown. CASE DESCRIPTION: Two siblings of a Taiwanese family with GRA were found to have adrenal adenomas and somatic KCNJ5 mutations. Complete clinical cure was achieved after unilateral adrenalectomy. Furthermore, the conversion site of the chimeric gene was identified by direct sequencing. CONCLUSIONS: We report the coexistence of a somatic KCNJ5 mutation and GRA. Patients with GRA whose blood pressure management develops resistance to glucocorticoid treatment could therefore benefit from a lateralization test. The promising outcomes after unilateral adrenalectomy presented in this report offer new perspectives for further research into various PA subtypes.

Are Older Adults without a Healthy Diet Less Physically Active and More Sedentary?

Few studies on older populations consider several energy balance-related behaviors together. This cross-sectional study compared subjectively and objectively measured physical activity (PA) and sedentary behavior (SB) patterns between older adults with and without a healthy diet. We recruited 127 community-dwelling older Taiwanese adults (69.9 ± 5.0 years); data were collected during April and September 2018. Objectively measured total PA, moderate-to-vigorous PA, light PA, step count, total sedentary time, duration of sedentary bouts, number of sedentary bouts, and number of sedentary breaks were assessed using activity monitors. Subjectively measured PA and SB were measured using the International Physical Activity Questionnaire and Sedentary Behavior Questionnaire for Older Adults. Chi-square tests and independent sample t-tests were performed. For subjective measures, older adults without a healthy diet spent significantly less total leisure time on PA and more leisure sitting time than those with a healthy diet. For objective measures, older adults without a healthy diet spent less time on light PA and had a higher total sedentary time, duration of sedentary bouts, times of sedentary bouts, and times of sedentary breaks than those with a healthy diet. Regardless of the use of objective or subjective measurements, older adults without a healthy diet engaged in a more inactive and sedentary lifestyle. These findings have implications for health promotion practitioners in designing tailored interventions.

Risk of severe erectile dysfunction in primary hyperaldosteronism: A population-based propensity score matching cohort study.

BACKGROUND: An elevated plasma aldosterone level has been reported as an independent risk factor for severe erectile dysfunction in men. The aim of this study was to explore whether primary hyperaldosteronism patients experience erectile dysfunction after targeted treatment. METHODS: We conducted a population-based cohort study of men with newly identified primary hyperaldosteronism/aldosterone-producing adenoma from January 1, 1997, to December 31, 2009. Men with essential hypertension and normotension were matched to the primary hyperaldosteronism group according to propensity score matching. RESULTS: We identified 1,067 men with primary hyperaldosteronism (mean age, 46.7 ± 12.8 years) and matched them with the same number of men with essential hypertension or normotension. During the mean follow-up interval of 5.4 years, the incident rates of total erectile dysfunction were 5.7, 3.9, and 3.1 per 1,000 person-years for the primary hyperaldosteronism, essential hypertension, and normotension groups, respectively. Men with primary hyperaldosteronism exhibited a higher risk of erectile dysfunction compared with men with normotension (competing risks hazard ratio, 1.83), and no difference was seen in comparison with men who have essential hypertension. After adrenalectomy, men who have primary hyperaldosteronism had a higher risk of exhibiting severe erectile dysfunction compared with men who have essential hypertension (competing risks hazard ratio, 2.44) or normotension (competing risks hazard ratio, 2.90). CONCLUSION: Men with primary hyperaldosteronism reported a higher incidence of severe erectile dysfunction than normotension controls despite targeted treatment. The risk of severe erectile dysfunction increased after men who have primary hyperaldosteronism underwent adrenalectomy. This result raises the possibility of severe erectile dysfunction after adrenalectomy and calls for a prospective large-scale study of men who have aldosterone-producing adenoma regarding their erectile function both before and after adrenalectomy.

Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus.

Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening ARR in PA patients with diabetes. The study enrolled consecutive patients and they underwent ARR testing at screening. Then the diagnosis of PA was confirmed from the Taiwan Primary Aldosteronism Investigation registration dataset. Generalized additive model smoothing plot was used to validate the performance of screening ARR in PA patients with or without diabetes. During this study period, 844 PA patients were confirmed and 136 (16.0%) among them had diabetes. Other 816 patients were diagnosed with essential hypertension and used as the control group and 89 (10.9%) among them had diabetes. PA patients with diabetes were older and had a longer duration of hypertensive latency, higher systolic blood pressure and lower glomerular filtration rate than those PA patients without diabetes. The cut-off value of ARR in the generalized additive model predicting PA was 65 ng/dL per ng/mL/h in diabetic patients, while 45 ng/dL per ng/mL/h in non-diabetic patients. There was a considerable prevalence of diabetes among PA patients, which might be capable of interfering with the conventional screening test. The best cut-off value of ARR, more than 65 ng/dL per ng/mL/h in PA patients with diabetes, was higher than those without diabetes.

miRNA-203 Modulates Aldosterone Levels and Cell Proliferation by Targeting Wnt5a in Aldosterone-Producing Adenomas.

Context: The aberrant expression or alternation of miRNA in the pathogenesis of aldosterone-producing adenomas (APAs) is still largely unknown. Objective: We investigated the role of miRNA-203 (screened from miRNA microarrays) and elucidated its effects on the Wnt/ß-catenin pathway regarding aldosterone production and cell proliferation in APAs. Methods: miR-203 expression was upregulated or downregulated by transfecting miR-203 mimics or inhibitors into primary APA cells, the human adrenocortical cell line HAC15, and C57BL/6 mice. In vitro and biochemical data were correlated with the respective clinical parameters of APAs to evaluate their clinical importance. Results: The expression of miR-203 in human APA samples was significantly lower than that of peritumor adrenal samples. Tumoral miR-203 abundance correlated negatively with both plasma aldosterone level and tumor size in patients with APAs. miR-203 inhibitors increased aldosterone production and cell proliferation in HAC15 cells, and restoration of expression via miR-203 mimics showed decreased cell proliferation and aldosterone hypersecretion in APA cell cultures. In vivo selective inhibition of miR-203 via intra-adrenal injection of miR-203 inhibitors in mice led to a substantial increase in systolic blood pressure and plasma aldosterone levels. Additionally, the dual-luciferase reporter assay demonstrated that WNT5A is a direct target of miR-203. Furthermore, plasma Wnt5a levels in adrenal vein sampling were helpful in differentiating tumor localization, and preoperative plasma Wnt5a levels predicted the cure of hypertension after adrenalectomy. Conclusion: We have demonstrated that attenuated miR-203 expression in APAs increases aldosterone production and the tumorigenesis of adrenal cells by activating the Wnt5a/ß-catenin pathway.