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Monitoring drinking water quality is essential to protect people's health and wellbeing. In the United States, the Safe Drinking Water Information System (SDWIS) database records the occurrence of a drinking water violation regulation in public water systems. A notable shortcoming of SDWIS is the lack of the contaminant concentration level about the allowable maximum contaminant threshold. In this study, we take advantage of both the SDWIS violation database and the contaminants sampling database at the state level to examine the drinking water quality of all kinds of drinking water systems in detail. We obtained sampling data (i.e., the concentration level of contaminants) of public water systems (PWSs) in Tennessee and explored the statistical distribution of contaminant concentration data in relation to the enforceable maximum regulatory contaminant level). We use both SDWIS violation records and actual concentrations of contaminants from the sampling data to study the factors that influence the drinking water quality of PWSs. We find that different types of violations were more frequent in (1) specific geological regions, (2) counties with PWSs that serve a larger population (10,000 to 100,000 people), and (3) places with abundant surface water, such as near a lake or major river. Additionally, the distribution of measured concentrations for many contaminants was not smooth but was punctuated by discontinuities at selected levels, such as at 50% of the maximum contaminant level. Such anomalies in the sampling data do not indicate violations, but more investigation is needed to determine the reasons behind the punctuated changes., Competing Interests: Declaration of competing interest The authors declare none.

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism., Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Aims: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS)., Methods and Results: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission., Conclusions: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive., Objectives: This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers., Methods: Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions., Results: Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients., Conclusions: Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The present study aimed to determine the prognostic impact of resting heart rate (HR) and systolic blood pressure (SBP) in takotsubo syndrome (TTS)., Methods and Results: Patients from the International Takotsubo Registry with complete data on HR and SBP were enrolled. We analysed all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) in tertiles of HR (<77 b.p.m., 77-94 b.p.m., >94 b.p.m.) and SBP (<119 mmHg, 119-140 mmHg, >140 mmHg). In addition, linear splines with interactions between HR and SBP were analysed. The risk of all-cause mortality was higher in the second HR tertile (1.89, 1.15-3.10; P = 0.012) and the third HR tertile (3.01, 1.90-4.79; P < 0.001) than in the first tertile. Similar effects were observed for MACCE. Low SBP was related to an increased risk of all-cause mortality (P < 0.001) and MACCE (P = 0.002). In a multivariable analysis of all-cause mortality, at HR >70 b.p.m., every 1 b.p.m. increase in HR was associated with a 1.7% increase (P < 0.001), and every 1 mmHg increase in SBP up to 130 mmHg was associated with a 2% risk reduction (P < 0.001). The risk of all-cause mortality thus was particularly elevated when low SBP occurred together with high HR., Conclusions: High HR and low SBP are associated with an increased risk of all-cause mortality in TTS. HR reduction might be worthy of being investigated as a therapeutic strategy for this condition and high HR and low SBP can be used to evaluate risk in this acute presentation of TTS., Clinical Trial Registration: ClinicalTrials.gov NCT01947621., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Aims: Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage., Methods and Results: Patients with TTS were recruited from the International Takotsubo Registry ( www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96-0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of ≥50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score ≤31 were diagnosed as ACS, ∼95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87-0.93)., Conclusion: The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity., Trial Registration: NCT0194762., (© 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: To explore the factors influencing cognitive functions in patients with childhood and adolescence-onset schizophrenia., Methods: The clinical data of 78 patients with childhood and adolescence-onset schizophrenia who met with the criteria of ICD-10 for schizophrenia were retrospectively reviewed. The cognitive functions were evaluated by the Chinese Wechsler Intelligence Scale for Children (C-WISC), the Wisconsin Card Sorting Test (WCST), digit span backward and P300. The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS)., Results: The patients with a lower education level or earlier onset of age had a longer P3 latency at the P300Fz area. The patients with a higher parental education level had higher scores of full intelligence quotient (FIQ), verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), conceptual level and completed categories of WCST and backward numeric order reciting. The patients with higher PANSS negative subscale scores had lower scores of FIQ, VIQ, PIQ, completed categories and conceptual level of WCST and backward numeric order reciting. The patients with a longer stabilization time had higher backward numeric order reciting scores., Conclusions: The severity of negative symptoms of the patients and the educational level of their parents are major factors influencing cognitive functions in patients with childhood and adolescence-onset schizophrenia.

Objective: To investigate the effect of parent training combined with methylphenidate treatment on family relationships in children with attention deficit/hyperactivity disorder (ADHD)., Methods: Fifty-nine parents of children with ADHD under methylphenidate treatment participated in a modified 5-week training program. The intervention effect was evaluated using the Conners Parent Symptom Questionnaire, ADHD Rating Scale-IV Home Version (ADHD-RS-IV Home Version), Caregiver Strain Questionnaire, Parent-Child Relationship Self-rating Scale and Piers-Harris Children's Self-Concept Scale. Parents also completed the training satisfaction survey before and after the intervention., Results: After the 5-week parent training, compared with the baseline values, total scores of Conners Parent Symptom Questionnaire and scores of conduct problems and anxiety significantly decreased, and scores of attention deficit, hyperactivity, impulsivity and oppositional defiant behaviors of ADHD-RS-IV Home Version, and Caregiver Strain Questionnaire total scores were all significantly decreased (P<0.05), while total scores of the Parent-Child Relationship Self-Rating Scale and Piers-Harris Children's Self-Concept Scale were significantly increased (P<0.05)., Conclusions: Modified 5-week parent training program may improve parent-child relationship and reduce parenting stress in ADHD families.

Objective: To compare resting-state functional magnetic resonance imaging (fMRI) findings of children with attention-deficit hyperactivity disorder (ADHD) and normal children, and to investigate the possible mechanism of brain dysfunction in children with ADHD., Methods: Resting-state fMRI was performed on 18 children who met the DSM-IV diagnostic criteria for ADHD (ADHD group) and 18 normal children (control group) matched for age, sex, IQ, degree of education and handedness. The two groups were compared in terms of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo)., Results: Compared with the control group, the ADHD group had decreased ALFF in the bilateral posterior lobes of the cerebellum and the left side of the pons, increased ALFF in the right precentral gyrus, decreased ReHo in the left medial frontal gyrus, right superior frontal gyrus, and left precuneus, and increased ReHo in the left anterior lobe of the cerebellum, left caudate nucleus, right parahippocampal gyrus, left precentral gyrus, and right middle frontal gyrus., Conclusions: In resting state, children with ADHD have decreased brain activity in some regions, including the cerebellum and frontal cortex, compared with normal children, which supports the hypothesis of dysfunctional fronto-cerebellar circuits in ADHD.

Objective: To investigate influential factors for the tendency to medicate and medication compliance in children with attention deficit hyperactivity disorder (ADHD)., Methods: A total of 188 children aged from 5 to 16 years, who were initially diagnosed with ADHD according to DSM-IV criteria, were included in the study. They underwent symptom assessment and cognitive function test. The compliance of methylphenidate treatment was evaluated., Results: Patients with better emotional state, and fewer oppositional and hyperactive behaviors and those who had a family history of psychiatric diseases and who obtained lower scores in the number cancellation test (NCT), were more prone to medication and/or exhibited better medication compliance. Logistic regression analysis showed that fewer oppositional and hyperactive behaviors and lower NCT scores were the predictive factors for a higher tendency to medicate, and a better emotional state was the predictive factor for better medication compliance. Patients of predominantly inattentive type were more prone to medication and showed better medication compliance, as compared with those of combined type. Gender, age and symptom severity were not associated with the tendency to medicate and/or medication compliance., Conclusions: There is a need to enhance medication compliance in children with ADHD who have hyperactive, impulsive and oppositional behaviors, and to improve their long-term social functions.

Fusarium asiaticum and F. graminearum are the primary causal agents of Fusarium head blight (FHB) of wheat in China. Carbendazim (a benzimadazole fungicide, MBC), has been extensively used for the control of FHB, resulting in severe MBC resistance in China. This article presents the baseline sensitivity of F. asiaticum and F. graminearum isolates from Anhui Province of China to fungicides pyraclostrobin (a quinone outside inhibitor) and epoxiconazole (a sterol demethylation inhibitor). In the presence of salicylhydroxamic acid, the 50% effective concentration (EC 50 ) values for pyraclostrobin in inhibiting mycelial growth of the 126 F. asiaticum isolates and 63 F. graminearum isolates were 0.012 to 0.135 μg/ml and 0.010 to 0.105 μg/ml, and the EC 50 values for pyraclostrobin in inhibiting conidium germination of the F. asiaticum and F. graminearum populations were 0.047 to 0.291 and 0.042 to 0.255 μg/ml, respectively. The EC 50 values for epoxiconazole in inhibiting mycelial growth of the F. asiaticum and F. graminearum populations were 0.12 to 0.95 and 0.16 to 0.93 μg/ml, respectively. All of the baseline sensitivity curves were unimodal. This study also suggested that there was no cross-resistance between MBC and pyraclostrobin or epoxiconazole. In the protective and curative tests, pyraclostrobin and epoxiconazole applied at 200 and 300 μg/ml exhibited over 75% protective and curative control efficacy in all treatments. In field trials, both pyraclostrobin and epoxiconazole at 225 g a.i./ha provided over 80% efficacy in 2010 and 2011 at both sites where MBC resistance occurred, suggesting excellent activity against FHB. Interestingly, integrated use of pyraclostrobin + epoxiconazole applied at 150 + 150 g a.i./ha provided over 85% efficacy at both sites in 2010 and 2011. Pyraclostrobin and epoxiconazole should be good alternatives to MBC for the control of FHB, and integrated use of these two fungicides might achieve greater efficacy.

Background: Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC., Methods: Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations., Results: Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05)., Conclusions: These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.

Objective: To scan for mutations of polycystic kidney disease 1 gene (PKD1) in Chinese population in order to find some features about Chinese patients and a better approach to detect mutations., Methods: Twenty-five PKD-affected individuals from twenty-one unrelated genealogies and sixteen controls participated in the study. Thirty-five blood samples and six tissues were obtained after receiving informed consent and were in accordance with institutional ethical guidelines. Genomic DNA was isolated from peripheral blood using standard procedures. PCR amplification of genomic DNA was performed to generate the aimed fragments. Amplified fragments were analyzed by denaturing gradient gel electrophoresis (DGGE). A GC clamp was attached to the 5' primer. After that, the abnormal fragments were sequenced on freshly amplified specific PCR products with the dideoxynucleotide chain termination method. Sequencing was performed for all samples to evaluate DGGE., Results: Aimed fragments of exons 44 and 45 were amplified. DGGE detected eleven abnormal PCR fragments. Two novel mutations were identified by sequencing, included one nonsense mutation (C12217T) and one frameshift (12431delCT). In addition, one polymorphism (A50747C) was identified. The mutation detection rate is 8% in our study., Conclusion: Two novel pathogenic mutations were detected, including one nonsense mutation (C12217T) and one frameshift (12431delCT).

A comparative retrospective study with follow-up survey was performed on 75 male bladder cancer patients, in order to investigate the relation between bladder carcinoma and bladder-neck obstruction, and effect of combined surgical treatment for both lesion on the recurrence of bladder cancer. All the bladder cancers were confirmed by cystoscopy and histopathological examination. The pathological findings included: 69 cases of transitional cell carcinoma, 5 cases of squamous cell carcinoma and 1 case of adenocarcinoma. All patients were treated by partial cystectomy and followed-up by cystoscopy and urine exfoliative cytologic examination. Thirty patients (group I) who had bladder cancer and bladder-neck obstruction received simultaneous partial cystectomy and cystauchenotomy were compared to 21 patients (group II) who had both lesions but received partial cystectomy only, and to 24 patients (group III) who had bladder cancer only and underwent partial cystectomy. Evaluation of recurrence of bladder cancer in each group showed that recurrence occurred in 6 patients (20%) in group I, 10 patients (47.1%) in group II, and 4 patients (16.6%) in group III. The data showed that partial cystectomy combined with cystauchenotomy in patients with bladder cancer accompanied by bladder-neck obstruction significantly decreased the postoperative recurrence of tumor in comparison with the group treated by partial cystectomy alone. It is suggested that the presence of bladder-neck obstruction may exert some effects on the genesis and postoperative recurrence of bladder cancer.