Association between clinical use of nifedipine and the risk of osteoporosis: a nationwide retrospective cohort study.

Nifedipine is one of the common calcium channel blockers (CCBs) for hypertension that induce peroxisome-proliferator-activated receptor γ coactivator 1-α, which is envisioned as a potential therapeutic target in bone disease. The findings of this retrospective cohort study suggest that patients who receive nifedipine may have a potential protective effect on osteoporosis in comparison to other CCBs. INTRODUCTION: Nifedipine was one L-type dihydropyridine calcium channel blocker (CCB) that can improve bone loss. However, epidemiological studies on the association between the use of nifedipine and osteoporosis risk are limited. Thus, this study aimed to evaluate the association between the clinical use of nifedipine and the risk of osteoporosis. METHODS: This retrospective cohort was conducted using the National Health Insurance Research Database of Taiwan from 2000 to 2013. The study includes 1225 patients receiving nifedipine (the exposed cohort) and 4900 patients receiving other CCBs (the comparison cohort). The primary outcome was the diagnosis of osteoporosis. The hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the association between the use of nifedipine and the risk of osteoporosis. RESULTS: Patients receiving nifedipine treatment had a reduced risk of osteoporosis as compared with those undergoing other CCB treatments (adjusted HR, 0.44; 95% CI, 0.37-0.53). Moreover, this inverse association is evident in both sexes and various age groups. CONCLUSIONS: This population-based cohort study demonstrated that nifedipine may have potential protective effect on osteoporosis compared with other CCBs. The clinical implications of the present study need further investigation.

Association between severity of dental caries and the risk of stroke.

OBJECTIVE: The relationship between dental caries and stroke remains inconclusive. The aim of this study is to investigate whether different severities of dental caries affect the risk of stroke. METHODS: This retrospective cohort study was conducted using the 2000-2013 Taiwan National Health Insurance Database. We selected 23,662 patients with advanced/severe dental caries and 23,662 patients with incipient/moderate dental caries between 2000 and 2006. These patients were followed to the occurrence of stroke or to the end of the study in 2013. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the Cox proportional hazards models were calculated to assess the association between severity of dental caries and the risk of stroke. RESULTS: The advanced/severe dental caries group had a significantly higher risk of stroke compared with incipient/moderate dental caries group (adjusted HR, 1.16; 95% CI, 1.03-1.31). Stratified analyses showed that advanced/severe dental caries was positively associated with the risk of ischemic stroke in patients aged ≥40 years and with the risk of hemorrhagic stroke in patients aged <40 years. CONCLUSION: There is a severity-dependent association between dental caries and stroke in an Asian population.

The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study.

BACKGROUND: The importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB. METHODS: This was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67). RESULTS: The loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan-Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups. CONCLUSIONS: The administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

The Long-Term Analgesic Effectiveness of Platelet-Rich Plasma Injection for Carpal Tunnel Syndrome: A Cross-Sectional Cohort Study.

OBJECTIVE: Interest in perineural platelet-rich-plasma (PRP) injections for the treatment of carpal tunnel syndrome (CTS) has increased in recent years. However, evidence supporting the long-term effectiveness of PRP is lacking. Therefore, the aim of our cross-sectional cohort study was to investigate the long-term results of PRP injections for CTS. METHODS: Eighty-one patients diagnosed with CTS of any grade who received a single PRP injection at least 2 years prior were enrolled. Through structured telephone interviews, all patients were asked of their post-injection outcomes compared to their pre-injection condition. Symptom relief ≥50%, compared to the pre-injection condition, was considered an effective outcome. Binary logistic regression was applied to analyze each baseline variable as a regressor for determining the prognostic outcome factors. RESULTS: In total, 70% of patients reported positive outcomes ≥2 years post-injection. Shorter duration of symptoms before treatment (odds ratio: 0.991; 95% confidence interval [CI] 0.983-0.999; P = .023) and lower electrodiagnostic severity of CTS were the main prognostic factors for an effective outcome (mild grade vs severe grade, odds ratio: 17.652; 95% CI 1.43-221.1; P = .025). Although there was a trend toward positive outcomes at longer follow-up durations (2-3 years vs 3-4 years vs 4-5 years), the difference was not statistically significant. CONCLUSIONS: A single perineural PRP injection has a long-term analgesic effect on CTS, especially in mild-to-moderate cases.

Adult abuse and poor prognosis in Taiwan, 2000-2015: a cohort study.

BACKGROUND: To investigate the risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, self-inflicted injury, and mortality after adult violence from 2000 to 2015 in Taiwan. METHODS: This study used data from National Health Insurance Research Database (NHIRD) on outpatient, emergency, and inpatient visits for two million people enrolled in the National Health Insurance (NHI) from 2000 to 2015. The case study defined ICD-9 diagnosis code N code 995.8 (abused adult) or E code E960-E969 (homicide and intentional injury of another). It analyzed first-time violence in adults aged 18-64 years (study group). 1:4 ratio was matched with injury and non-violent patients (control group). The paired variables were sex, age (± 1 year), pre-exposure to the Charlson comorbidity index, and year of medical treatment. Statistical analysis was conducted using SAS 9.4 and Cox regression for data analysis. RESULTS: In total, 8,726 individuals experienced violence (case group) while34,904 did not experienced violence (control group) over 15 years. The prevalence of poor prognosis among victims of violence was 25.4/104, 31.3/104, 10.5/10,4 and 104.6/104 for schizophrenic disorders, psychotic disorders, suicide or self-inflicted injury and mortality, respectively. Among adults, the risks of suicide or self-inflicted injury, schizophrenic disorders, psychotic disorders, and mortality after exposure to violence (average 9 years) were 6.87-, 5.63-, 4.10-, and 2.50-times (p < 0.01), respectively, compared with those without violence. Among males, the risks were 5.66-, 3.85-, 3.59- and 2.51-times higher, respectively, than those without violence (p < 0.01), and they were 21.93-, 5.57-, 4.60- and 2.46-times higher than those without violence (p < 0.01) among females. CONCLUSION: The risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, or self-inflicted injury and mortality after adult violence was higher than in those who have not experienced a violent injury. Adults at the highest risk for violent suicide or self-inflicted injuries due to exposure to violent injuries -males were at risk for schizophrenia and females were at risk for suicide or self-inflicted injuries. Therefore, it is necessary for social workers and medical personnel to pay attention to the psychological status of victims of violence.

Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer.

The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar's test were used for group comparisons, and Kaplan-Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38-7.73 for RFS, HR = 2.35 and 95% CI = 1.17-4.71 for PFS, HR = 4.32 and 95% CI = 1.8-10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07-5.08 for RFS, HR = 2.42 and 95% CI = 1.19-4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

The Epidemiology of Entamoeba histolytica Infection and Its Associated Risk Factors among Domestic and Imported Patients in Taiwan during the 2011-2020 Period.

Background and Objectives: Amebiasis remains an important public health problem worldwide, and immigration and increased international travel have affected incident disease cases. This study assesses the prevalence of Entamoeba histolytica in Taiwan between 2011 and 2020 by analyzing data from surveillance programs conducted by the Centers for Disease Control of Taiwan (TCDC) on laboratory-confirmed cases. Materials and Methods: The E. histolytica infection-related data reported to the National Infectious Diseases Statistics System at the TCDC from 1 January 2011 to 31 December 2020 were collected, including age, gender, place of residence, and the geographic season of exposure for each case. Results: In total, 3066 cases with E. histolytica infections were included in our analysis. Among them, 1735 (57%) cases were imported, and 1331 (43%) were locally acquired. The average annual incidence rate of E. histolytica infections in Taiwan between 2011 and 2020 was 10.6 and 16.1 per 1,000,000 patients. There were statistical differences in gender, age group, and place of residence (p < 0.001) by the source distribution of cases. Also, these differences were found every year (p < 0.05). There were statistical differences in gender and age group (p < 0.001) by place of residence (p < 0.001). The only difference between the distribution of cases and age group was in gender (p < 0.001). Eight patients with amebiasis died, and the fatality rate was 0.3% (8/3066), of whom 75% (6/8) were male, and 75% (6/8) were over 45 years old. This study demonstrates that multiple linear regression analysis shows positive associations between NO2 concentration and amebiasis cases (B value = 2.569, p = 0.019), O3 concentration and amebiasis cases (B value = 0.294, p = 0.008), and temperature and amebiasis cases (B value = 1.096, p = 0.046). Conclusions: This study is the first report of confirmed E. histolytica cases from TCDC surveillance data between 2011 and 2020. This study showed the importance of long periods, air pollutants, and geographically comprehensive analysis for estimating the effect of amebiasis transmission in Taiwan's populations.

Human Papillomavirus and Risk of Colorectal Cancer: An Analysis of Nationwide Claims Data.

Background and Objectives: Although human papillomavirus (HPV) is a major etiology of cervical and anogenital cancers, whether it is associated with colorectal carcinogenesis is yet undetermined. Materials and Methods: The longitudinal association of HPV infection with colorectal cancer (CRC) was evaluated using 2000-2013 data from a nationwide Taiwanese claims database. In this retrospective cohort study, 358 patients with primary HPV diagnoses (HPV-infected cohort) and 1432 patients without such a diagnosis (HPV-uninfected cohort) were recruited between 2000 and 2006. Both cohorts were followed up to identify CRC incidences from 2006 to 2013. Hazard ratios (HRs) and their 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to estimate the association between HPV and CRC risk. Results: The HPV-infected cohort had a significantly higher cumulative incidence of CRC than the HPV-uninfected cohort. The presence of HPV was associated with an increased risk of CRC (adjusted HR, 1.63; 95% CI, 1.02-3.62). Furthermore, the significant HPV-CRC risk association was evident in both sexes. Conclusions: This population-based cohort study reveals longitudinal evidence that HPV is associated with an increased risk of CRC. Further studies are required to verify the role of HPV in colorectal carcinogenesis.

Association between gastroesophageal reflux disease and colorectal cancer risk: a population-based cohort study.

PURPOSE: Several studies have investigated the association between gastroesophageal reflux disease (GERD) and colorectal cancer (CRC) risk, but the presented scientific results are highly debatable. This study examined the longitudinal association between GERD and CRC in an Asian population. METHODS: A retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. The study cohort comprised 45,828 individuals with newly diagnosed GERD (the GERD cohort) and 229,140 age, sex, and date of enrollment-matched patients without GERD (the comparison cohort) from 2000 to 2006. The primary outcome was the incidence of CRC. To estimate the effect of GERD on the risk of CRC, the Cox proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 785 newly diagnosed CRC patients in the 45,828 patients with GERD. Relatively, there were 2375 incident CRC cases in 229,140 patients without GERD. The incidence rate of CRC for the GERD cohort (17.60 per 10,000 person-years) was significantly higher than the corresponding incidence rate for the comparison cohort (10.22 per 10,000 person-years). After adjustment for confounders, GERD was associated with a significantly increased risk of CRC (adjusted HR,1.76; 95% CI, 1.62-2.90). Of note, a significant association between GERD and CRC risk was evident in both genders. CONCLUSIONS: In conclusion, this nationwide population-based cohort study supports the hypothesis that GERD was associated with a significantly increased risk of CRC. Our findings warrant still further investigation of the underlying mechanisms related to carcinogenic effect of GERD on colorectal carcinoma.

One-Year Efficacy of Platelet-Rich Plasma for Moderate-to-Severe Carpal Tunnel Syndrome: A Prospective, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To assess the therapeutic effect of platelet-rich plasma (PRP) for moderate-to-severe carpal tunnel syndrome (CTS). DESIGN: A prospective, randomized, double-blinded, controlled trial (1-year follow-up). SETTING: Outpatient of local medical center settings. PARTICIPANTS: Patients (N=26) who were diagnosed with bilateral moderate-to-severe CTS (total 52 wrists) were included. For each patient, one wrist was randomized into either the PRP or control group and the contralateral wrist of the same patient was allocated to another group. Twenty-four patients were included in the final data analysis. INTERVENTIONS: The wrists in the PRP group received a single ultrasound-guided dose of PRP injection (3.5mL), and the control group received a single ultrasound-guided injection with normal saline (3.5mL). MAIN OUTCOME MEASURES: The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores were used as the primary outcome. Secondary outcomes encompassed the cross-sectional area of the median nerve and electrophysiological study. Assessments were conducted prior to injection and 1, 3, 6, and 12 months postinjection. RESULTS: Compared to the control group, the PRP group exhibited significant improvements in BCTQ severity scores at all time points, BCTQ functional scores at the sixth month, and cross-sectional area at the 12th month postinjection (P<.0125). CONCLUSIONS: A single dose of ultrasound-guided perineural PRP injection can provide therapeutic effect for 1 year postinjection.

Outcome predictors of platelet-rich plasma injection for moderate carpal tunnel syndrome.

INTRODUCTION: Platelet-rich plasma (PRP) injection is effective for mild-to-moderate carpal tunnel syndrome (CTS), and physicians have been using PRP injections to treat CTS. However, the predictive factors of PRP injections have not been evaluated. This retrospective study sought to identify the predictive factors of PRP injections in patients with moderate CTS. METHODS: Seventy-one patients with moderate CTS receiving single PRP injections were enrolled. The outcomes at the third- and sixth-month postinjection visits were categorised into good and poor groups according to the following: (1) good outcome, with visual analogue scale (VAS) score decrease ≧50% and (2) poor outcome, with VAS score decrease <50% of preinjection scores. Significant variables between groups were entered into a binary logistic regression to determine the predictive factors. RESULTS: The baseline body weight (BW), distal motor latency (DML), sensory nerve conduction velocity (SNCV), and cross-sectional area (CSA) of the median nerve were significantly different between the groups in the third month. The odds ratios (ORs) of all features were significant, except for SNCV (BW, OR: 0.911; P = .016; DML, OR: 0.383; P = .028; CSA, OR: 0.694; P = .003), and they remained significant in the sixth month (BW, OR: 0.909; P = .004; DML, OR: 0.530; P = .011; CSA, OR: 0.828; P = .032). CONCLUSION: Lower BW, DML, and CSA values of the median nerve predict better outcomes after perineural injection of PRP for moderate CTS at the 3- and 6-month follow-ups.

Positive association of Parkinson's disease with ankylosing spondylitis: a nationwide population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson's disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. METHODS: A population-based matched cohort study was performed using data from the 2000-2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. RESULTS: This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p < .001). Particularly, AS cohort to non-AS cohort relative risk of PD significantly increased for the patients aged below 49 and above 65 years (aHR 4.70, p < .001; aHR 1.69, p < .001, respectively) and the patients with and without comorbidities (aHR 1.61, p < .001; aHR 2.71, p < .001, respectively). Furthermore, NSAID use was associated with lower risk of PD (aHR 0.69, p < .05). However, the risk of PD was higher (aHR 2.40, p < .01) in patients with AS receiving immunosuppressants than in those not receiving (aHR 1.70, p < .001). CONCLUSIONS: Patients with AS had an increased risk of PD which might be related to underlying chronic inflammation. Further research is required to elucidate the underlying mechanism.

Apolipoprotein B Level and the Apolipoprotein B/Apolipoprotein A-I Ratio as a Harbinger of Ischemic Stroke: A Prospective Observation in Taiwan.

AIM: Prospective studies indicate that apolipoprotein (apo) measurements predict coronary heart disease risk. However, few population-based follow-up studies have addressed the predictive value of apo measurements in stroke risk. The aims of the present study were to analyze the predictive ability of apo measurements in the risk of ischemic stroke. METHODS: Serum apo A-I and apo B levels and calculated apo B/apo A-I ratio were measured at baseline in 2002 in a cohort of 4,204 participants who were followed for a mean of 4.61 years for a stroke event. RESULTS: After adjustment for potential confounders, a significantly stepwise increase in the incidence rate of stroke across quartiles of both apo B and the apo B/apo A-I ratio was evident in both genders and across age-groups. The predictive ability of apo B to detect ischemic stroke was comparable with that of the apo B/apo A-I ratio. Furthermore, both apo B and the apo B/apo A-I ratio were better predictors of the risk of ischemic stroke than total cholesterol (TC), low-density lipoprotein cholesterol, and the TC/high-density lipoprotein cholesterol ratio. CONCLUSIONS: This cohort study demonstrates that apo B and the apo B/apo A-I ratio were a significant risk predictor of stroke. Furthermore, the predictive ability of apo B and the apo B/apo A-I ratio in stroke risk was better than routine clinical lipid measurements. Thus, measurements of apolipoproteins have superior clinical utility over traditional lipid measurements in identifying subjects at risk for ischemic stroke.

Risk factors for complications of percutaneous ultrasound-guided renal biopsy in children.

BACKGROUND: Percutaneous ultrasound-guided renal biopsy (PURB) is an invasive but essential procedure in establishing the histologic diagnosis of pediatric renal diseases. Large studies which describe PURB complications and its contributory risk factors are scarce in the pediatric literature. METHODS: Patients who underwent real-time PURB from September 2011 to August 2017 were retrospectively reviewed. Data pertaining to clinical characteristics, histologic diagnosis and biopsy-related complications were collected. In addition, the risk factors for complications were also analyzed. RESULTS: Overall, 183 patients (109 females) were enrolled and 201 biopsies were obtained. The mean age was 14.4 ± 13.7 years. Over 98% of the biopsies were considered adequate in quality. The major complications were perirenal hematoma requiring blood transfusion (4 cases, 2.0%), followed by perirenal abscess (1 case, 0.5%) and arteriovenous fistula (1 case, 0.5%). All patients recovered without sequelae after treatment. Hypertension, low estimated glomerular filtration rate (eGFR) and anemia were more common in patients with complication than in those without. Further logistic regression model analysis demonstrated that eGFR <30 ml/1.73m2/min was an independent risk factor for major complications. CONCLUSIONS: Perirenal hematoma needing blood transfusion is the most common major complication for children undergoing renal biopsy. Low eGFR is an independent risk factor for major complications. Early recognition and timely treatment should be delivered to children with renal function impairment accordingly.

The Effectiveness of Platelet-Rich Plasma and Radial Extracorporeal Shock Wave Compared with Platelet-Rich Plasma in the Treatment of Moderate Carpal Tunnel Syndrome.

OBJECTIVES: To evaluate the combination effect of platelet-rich plasma (PRP) and extracorporeal shock wave therapy (ESWT) for moderate carpal tunnel syndrome (CTS), compared with PRP alone. DESIGN: A randomized, double-blinded, placebo-controlled trial. SETTING: A single medical center in Taiwan. PATIENTS: Patients diagnosed with moderate CTS. INTERVENTIONS: All subjects were administered one dose of ultrasound-guided PRP injection at baseline. After two weeks, one session of rESWT was completed in the intervention group, whereas the control group received one session of sham rESWT. Evaluations were performed at baseline and one, three, and six months post-PRP injection. OUTCOME MEASURES: The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) was measured as the primary outcome. Electrophysiological study and cross-sectional area (CSA) of the median nerve were used as secondary outcomes. RESULTS: All 40 enrolled subjects (male/female: 4/36) completed the study, resulting in an analysis of 32 wrists per group (total: N = 64 wrists). Compared with the control group, the intervention group did not show statistically significantly superior outcomes, except in BCTQs at one month (mean change ± SE = -11.47 ± 1.18 vs -7.06 ± 1.26, P = 0.013) and distal motor latency at three months (mean change ± SE = -0.59 ± 0.09 vs -0.30 ± 0.09, P = 0.031). CONCLUSIONS: Combined PRP and one-session rESWT was not superior to PRP alone in treating moderate CTS. Further studies with multiple sessions of ESWT and longer follow-up periods are needed to verify the clinical efficacy of ESWT.

Utility of apolipoprotein measurements in predicting incident type 2 diabetes: A Chinese cohort study.

BACKGROUND/PURPOSE: There is conflicting data regarding the utility of measuring apolipoproteins in addition to traditional lipid measures in risk assessment of cardiometabolic diseases. The aim of this study was to determine whether apolipoprotein measurements can improve the ability to predict the future development of type 2 diabetes beyond what is possible based on traditional type 2 diabetes risk factors and clinical routine lipid measurements. METHODS: A total of 4,223 Chinese adults without diabetes were followed for a mean duration of 5.42 years. The hazard ratios (HRs) with 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to analyze the longitudinal associations of apolipoprotein B (apo B), apolipoprotein A-I (apo A-I), and the apo B/apo A-I ratio with the risk of type 2 diabetes. Further, the analysis of the area under receiver operating characteristics curves (AUC) was performed to test the predictive value of apolipoprotein measurements. RESULTS: After adjusting for potential confounders, the HRs of diabetes consistently showed an increasing trend across both the apo B and the apo B/apo A-I ratio quartiles (p for trend = 0.004). In analyses of AUC, the predictive ability for type 2 diabetes risk for the apo B and the apo B/apo A-I ratio was superior to that of routine lipid and lipoprotein measurements. CONCLUSION: Apolipoprotein measurements significantly predict diabetes risk in an Asian population. Furthermore, the predictive ability of apo B alone to detect diabetes was comparable with that of the apo B/apo A-I ratio and better than the routine lipid measurements.

NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer.

Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified NKX6.1 hypermethylation as a promising marker and demonstrated that the NKX6.1 gene functions as a metastasis suppressor through the epigenetic regulation of the epithelial-to-mesenchymal transition (EMT) in cervical cancer. More recently, we have demonstrated that NKX6.1 methylation is related to the chemotherapy response in colorectal cancer (CRC). Nevertheless, the biological function of NKX6.1 in the tumorigenesis of CRC remains unclear. In this study, we showed that NKX6.1 suppresses tumorigenic and metastatic ability both in vitro and in vivo. NKX6.1 represses cell invasion partly through the modulation of EMT. The overexpression of NKX6.1 enhances chemosensitivity in CRC cells. To further explore how NKX6.1 exerts its tumor-suppressive function, we used RNA sequencing technology for comprehensive analysis. The results showed that differentially expressed genes (DEGs) were mainly related to cell migration, response to drug, transcription factor activity, and growth factor activity, suggesting that these DEGs are involved in the function of NKX6.1 suppressing cancer invasion and metastasis. Our results demonstrated that NKX6.1 functions as a tumor suppressor partly by repressing EMT and enhancing chemosensitivity in CRC, making it a potential therapeutic target.

Release parameters during progressive degeneration of dopamine neurons in a mouse model reveal earlier impairment of spontaneous than forced behaviors.

To determine the role of reduced dopaminergic transmission for declines of forced versus spontaneous behavior, we used a model of Parkinson's disease with progressive degeneration of dopamine (DA) neurons, the MitoPark mouse. Mice were subjected to rotarod tests of motor coordination, and open field and cylinder tests for spontaneous locomotor activity and postural axial support. To measure DA release in dorsal striatum and the shell of Nucleus Accumbens (NAc), we used ex vivo fast-scan cyclic voltammetry in 6- to 24-week-old mice. To determine decline of DA transporter function, we used 18FE-PE2I positron emission tomography. We show here that fast-scan cyclic voltammetry is a sensitive tool to detect evoked DA release dysfunction in MitoPark mice and that electrically evoked DA release is affected earlier in nigrostriatal than mesolimbic DA systems. DA reuptake was also affected more slowly in NAc shell. Positron emission tomography data showed DA uptake to be barely above detection levels in 16- and 20-week-old MitoPark mice. Rotarod performance was not impaired until mice were 16 weeks old, when evoked DA release in striatum had decreased to ≈ 40% of wild-type levels. In contrast, impairment of open field locomotion and rearing began at 10 weeks, in parallel with the initial modest decline of evoked DA release. We conclude that forced behaviors, such as motivation not to fall, can be partially maintained even when DA release is severely compromised, whereas spontaneous behaviors are much more sensitive to impaired DA release, and that presumed secondary non-dopaminergic system alterations do not markedly counteract or aggravate effects of severe impairment of DA release. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Correlation between kidney transplantation and colorectal cancer in hemodialysis patients: A nationwide, retrospective, population-based cohort study.

BACKGROUND: Kidney transplantation (KT) correlates with an increased risk of developing several malignancies; however, the risk of colorectal cancer (CRC) after KT remains debatable and has been marginally explored. Hence, in this nationwide, retrospective, population-based cohort study, we aimed to examine the correlation between KT and CRC in a large-scale population-based Chinese cohort. METHODS: We identified a total of 3739 regular hemodialysis patients undergoing KT (exposed cohort) and 42,324 hemodialysis patients not undergoing KT (non-exposed cohort) between 2000 and 2008 from Taiwan's National Health Insurance Research Database (NHIRD). Both cohorts were followed up from January 1, 2000, to the date of CRC diagnosis, death, or the end of 2013. Using Kaplan-Meier method, we measured the cumulative incidence of CRC in each cohort. Furthermore, Cox proportional hazards models were used to compute hazards ratios (HRs) and 95% confidence intervals (CIs) to estimate the correlation between KT and CRC in hemodialysis patients. RESULTS: The Kaplan-Meier analysis revealed that the cumulative incidence of CRC was significantly higher in the exposed cohort than in the non-exposed cohort (log-rank test, P < 0.001). After adjusting for potential confounders, the exposed cohort exhibited a significantly increased risk of CRC compared with the non-exposed cohort (adjusted HR, 1.34; 95% CI, 1.11-1.62). CONCLUSIONS: Hemodialysis patients undergoing KT have a significantly higher risk of CRC than those not undergoing KT. Cancer should continue to be a primary focus of prevention during KT.

O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.

Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression. Using transcriptomic analysis of prostate cancer data sets, histopathologic examination of clinical specimens, and in vivo experiments of xenograft models, we reveal in this study a coordinated increase in glycan-binding protein, galectin-4, specific glycosyltransferases of core 1 synthase, glycoprotein- N-acetylgalactosamine 3-ß-galactosyltransferase 1 (C1GALT1) and ST3 beta-galactoside α-2,3-sialyltransferase 1 (ST3GAL1), and resulting mucin-type O-glycans during the progression of CRPC. Furthermore, galectin-4 engaged with C1GALT1-dependent O-glycans to promote castration resistance and metastasis by activating receptor tyrosine kinase signaling and cancer cell stemness properties mediated by SRY-box 9 (SOX9). This galectin-glycan interaction up-regulated the MYC-dependent expression of C1GALT1 and ST3GAL1, which altered cellular mucin-type O-glycosylation to allow for galectin-4 binding. In clinical prostate cancer, high-level expression of C1GALT1 and galectin-4 together predict poor overall survival compared with low-level expression of C1GALT1 and galectin-4. In summary, MYC regulates abnormal O-glycosylation, thus priming cells for binding to galectin-4 and downstream signaling, which promotes castration resistance and metastasis.-Tzeng, S.-F., Tsai, C.-H., Chao, T.-K., Chou, Y.-C., Yang, Y.-C., Tsai, M.-H., Cha, T.-L., Hsiao, P.-W. O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.