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Yi-Hua Wu,1 Jen-Wei Chou,1– 4 Hsiang-Chun Lai,5 Gin-Shen Su,1 Ken-Sheng Cheng,1,2 Tsung-Wei Chen6 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, China Medical University Hospital, Taichung, Taiwan; 3Taiwan Society of Inflammatory Bowel Disease, Taipei, Taiwan; 4Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan; 5Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 6Department of Pathology, Asia University Hospital, Taichung, TaiwanCorrespondence: Jen-Wei Chou Division of Gastroenterology and Hepatology, Department of Internal Medicine. China Medical University Hospital, No. 2, Yude Road, North District, Taichung 40447, TaiwanTel + 886-4-22052121 ext. 2220Fax +886-4-22023119Email codecol@yahoo.com.twBackground: Patients with hyperkalemia are commonly treated with Kayexalate or Kalimate. Both drugs are associated with some fatal gastrointestinal (GI) adverse events (AEs).Aim: To assess the clinical characteristics and outcomes of GI AEs induced by Kayexalate or Kalimate from published case reports.Methods: We conducted a systematic review of case reports of Kayexalate or Kalimate-induced GI AEs, from PubMed, Medline, Cochrane Library, Clinical Key, and Google Scholar databases (1948 to March 31, 2020). We analyzed the clinical characteristics, GI AEs, and risk factors of enrolled patients.Results: We identified 41 published articles describing 135 cases of GI AEs induced by Kayexalate (103 cases) or Kalimate (32 cases). The mean age of all patients was 55.5 years. Most patients were male (54.8%). As high as 55.6% preparations were administered with sorbitol whereas 44.4% preparations had no sorbitol. The average time causing GI AEs was 19.8 days. Colon was the most commonly affected site (76.3%). Drug crystals were histopathologically proven in 95.5% of the patients. Meanwhile, mortality was reported in 20.7%.Conclusion: Kayexalate or Kalimate, without or with sorbitol combination, may be related to fatal GI damage. Uremia, hypertension, and transplantation are predisposing factors. Clinicians should be careful in prescribing Kayexalate or Kalimate to patients.Keywords: gastrointestinal injury, hyperkalemia, Kayexalate, Kalimate

Primary Klebsiella pneumoniae liver abscess with metastatic complications is a globally emerging infectious disease and is the leading cause of liver abscess in Taiwan. Host immunity and bacterial virulence, especially of the capsular polysaccharide type, are important in determining clinical manifestations. Investigators retrospectively studied the K pneumoniae genotype and capsular serotype from patients with 37 strains of liver abscess; no correlation was noted with genotype, and many genetically different strains caused liver abscess. Although K pneumoniae is prevalent in patients with diabetes, it can attack healthy or alcoholic people as well. Additional studies are needed to explore the mechanisms of bacterial virulence and to optimize treatment strategies. Physicians should be alert to the illness and its complications. [ABSTRACT FROM AUTHOR]

SUMMARY A dermold cyst, arising from the posterior aspects of the prostate and seminal vesicles, and extending into the pelvis to masquerade as a full bladder, must be exceedingly rare. Ultrasound, computed tomography and especially magnetic resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI in particular was very useful in providing an anatomical road map for surgery. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) is considered a potential therapeutic instrument for Alzheimer's disease (AD) because it affects long-term synaptic plasticity through the processes of long-term potentiation and long-term depression, thereby improving cognitive ability. Nevertheless, the efficacy of tDCS in treating AD is still debated. Dorsal lateral prefrontal cortex is the main role in executive functions., Objective: We investigate the cognitive effects of tDCS on AD patients., Methods: Thirty mild AD patients aged 66-86 years (mean = 75.6) were included in a double-blind, randomized, sham-controlled crossover study. They were randomly assigned to receive 10 consecutive daily sessions of active tDCS (2 mA for 30 min) or a sham intervention and switched conditions 3 months later. The anodal and cathodal electrodes were placed on the left dorsal lateral prefrontal cortex and the right supraorbital area, respectively. Subjects underwent various neuropsychological assessments before and after the interventions., Results: The results showed that tDCS significantly improved Cognitive Abilities Screening Instrument scores, especially on the items of "concentration and calculation", "orientation", "language ability", and "categorical verbal fluency". Mini-Mental State Examination and Wisconsin Card Sorting Test scores in all domains of "concept formation", "abstract thinking", "cognitive flexibility", and "accuracy" also improved significantly after tDCS. For the sham condition, no difference was found between the baseline scores and the after-intervention scores on any of the neuropsychological tests., Conclusion: >: Using tDCS improves the cognition of AD patients. Further large size clinical trials are necessary to validate the data.

Background: Idiopathic mesenteric phlebosclerosis is a rare condition with unclear pathogenesis. This study aimed to investigate the clinical features, diagnostic modalities, treatments, and outcomes of idiopathic mesenteric phlebosclerosis patients in Taiwan., Methods: Idiopathic mesenteric phlebosclerosis patients diagnosed by the typical characteristic of tree-like mesenteric venous calcifications on plain abdominal radiography or computed tomography between January 1992 and July 2021 were retrospectively analyzed., Results: Totally, 36 idiopathic mesenteric phlebosclerosis patients were enrolled (50% females; mean age, 61.6 years). Among the included patients, 26 (72.2%) and 10 (27.7%) were symptomatic and asymptomatic, respectively. Abdominal pain (61.1%) accounted for the majority of all symptoms, followed by fever, diarrhea, and bloody stools. Our results showed that 83.3% of patients had at least 1 risk factor, whereas 16.6% of patients had none. Moreover, among the included patients, 36.1%, 44.4%, 50.0%, 38.8%, and 8.3% had cardiovascular disease, chronic renal disease, cancer, chronic liver disease, and diabetes mellitus, respectively. Our findings showed 94.4% of patients were diagnosed via abdominal computed tomography and plain abdominal radiography, whereas 5.6% of patients were diagnosed via plain abdominal radiography. The ascending colon was the most commonly involved site (100%). Our findings showed that 91.6% of patients experienced good recovery after conservative treatment, except for the 3 who died of sepsis and respiratory failure. By contrast, 8.3% of idiopathic mesenteric phlebosclerosis patients underwent colectomy. The average follow-up duration was 62.5 months., Conclusions: Idiopathic mesenteric phlebosclerosis remains a rare disease in Taiwan. Plain abdominal radiography and computed tomography can be utilized for establishing a definite diagnosis. Conservative treatment is usually adequate for most patients, with surgical treatment only indicated for severe cases.

Introduction: Cecal intubation may be unsuccessful by conventional colonoscopy in some patients. Single-balloon-assisted colonoscopy (SBC) and cap-assisted colonoscopy (CAC) were studied to solve this problem. There was no head-to-head comparison between them., Methods: We conducted a randomized study from 2018 to 2021 to compare cecal intubation rate of SBC and CAC in patients with previous incomplete conventional colonoscopy. We recruited patients with incomplete conventional colonoscopy in two hospitals in Hong Kong. Patients were randomized into SBC group and CAC group in 1:1 ratio. In the case of failure in cecal intubation by allocated method, alternative modality would be performed as rescue., Results: Forty-four patients were recruited. Cecal intubation rate was superior in SBC group (22/22, 100%) than CAC group (16/22, 72.7%) (P = 0.02). No difference in cecal intubation time, polyp detection rate, and diagnostic gain in area not examined previously. SBC induced less discomfort (modified Gloucester comfort score 2.14 vs 2.63, P = 0.03) with use of comparable amount of midazolam and fentanyl as CAC. For patients failed cecal intubation by CAC, all (n = 6) were rescued successfully by SBC. Body weight, body mass index (BMI), and waist circumference were greater in rescue subgroup. More patients were obese (BMI ≥ 25 kg/m) in rescue subgroup (67% vs 19%). None in rescue subgroup had history of successful cecal intubation by conventional colonoscopy (0% vs 56%, P = 0.046). However, we failed to demonstrate significant association in multivariate analysis owing to small sample size. No adverse event was noted., Conclusion: SBC is superior to CAC in cecal intubation in patients with previous incomplete conventional colonoscopy., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Acute respiratory distress syndrome (ARDS) is characterized by acute-onset rapid-deteriorating inflammatory lung injury. Although the preservation of spontaneous breathing may have physiological benefits in oxygenation, increasing evidence shows that vigorous spontaneous breathing may aggravate lung injury (i.e., patient self-inflicted lung injury). Increased lung stress and pendelluft, which is defined as intrapulmonary gas redistribution without a significant change in tidal volume, are important mechanisms of patient self-inflicted lung injury. The presence of pendelluft may be considered a surrogate marker of vigorous inspiratory effort, which can cause the dependent lung to overstretch. In this review, we summarized three major methods for electrical impedance tomography-based pendelluft monitoring. Future studies are warranted to compare and validate the different methods of pendelluft estimation in patients with ARDS.

Objective: Moderate and severe behavioral and psychological symptoms of dementia (BPSD) often need medical treatment to improve symptoms. Agomelatine is a selective melatonergic (MT1/MT2) agonist that has normalizing effects on disturbed circadian rhythms and disrupted sleep-wake cycles. Its activity of 5HT-2C receptor antagonism is associated with lessening depression and anxiety and increasing slow-wave sleep. Based on past clinical records and current findings it suggests that agomelatine can improve BPSD for patients. This retrospective cohort study was designed to compare the BPSD before and after using agomelatine., Methods: Records of dementia cases who had ever received agomelatine treatment for BPSD in a general hospital setting during the past 2.5 years were identified and reviewed. Scores from before and after 3 months of treatment with agomelatine were collected for Neuropsychiatric Inventory (NPI), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) to compare and analyze the difference of psychological and behavioral symptoms pre- and post-agomelatine used., Results: Records of 144 cases of dementia with BPSD who had ever used agomelatine from January 2015 to June 2017 were collected. All of the 112 cases had BPRS and CGI scores, of which 75 cases had additional NPI scores. Among these 112 cases, the BPRS and CGI scores were significantly improved in all types of dementia. NPI scores indicated that the use of agomelatine alleviated obvious symptoms and decreased overall distress, especially in the depression/poor mood, anxiety, and sleep/night behavior., Conclusion: It is consistent with an effective result of agomelatine in improving BPSD.

Aorto-right-atrial fistula is an uncommon condition with an unclear pathogenesis. We present the case of a 3-year-old girl with a giant omphalocele repaired days after birth and incidentally discovered with a celiacomesenteric trunk-to-right atrium fistula. Three-dimensional reconstruction CT unveiled its anatomical pattern, and the fistula was successfully closed using a Amplatzer vascular plug II percutaneously.

Fast radio bursts (FRBs) are cosmic sources emitting millisecond-duration radio bursts. Although several hundreds FRBs have been discovered, their physical nature and central engine remain unclear. The variations of Faraday rotation measure and dispersion measure, due to local environment, are crucial clues to understanding their physical nature. The recent observations on the rotation measure of FRB 20201124A show a significant variation on a day time scale. Intriguingly, the oscillation of rotation measure supports that the local contribution can change sign, which indicates the magnetic field reversal along the line of sight. Here we present a physical model that explains observed characteristics of FRB 20201124A and proposes that repeating signal comes from a binary system containing a magnetar and a Be star with a decretion disk. When the magnetar approaches the periastron, the propagation of radio waves through the disk of the Be star naturally leads to the observed varying rotation measure, depolarization, large scattering timescale, and Faraday conversion. This study will prompt to search for FRB signals from Be/X-ray binaries., (© 2022. The Author(s).)

Objectives: To evaluate the Mental Health Youth Ambassador Programme between 2016 and 2019 in terms of participants' improvement in attitudes towards individuals with depression or psychosis., Methods: This anti-stigma programme was provided to secondary students (form 3 and above) and comprised three levels. Level 1 involved attending lectures about mental health; level 2 and level 3 involved social contact with persons-in-recovery. Students' attitudes towards those with depression and those with psychosis were assessed at baseline and after completion of each level of programme using the Chinese version of the Social Distance Scale., Results: Only 25 students who were assessed at all four time points were included in analysis. The mean Social Distance Scale scores for attitudes towards depression and psychosis improved significantly across all time points. Specifically, significant improvement occurred after completion of level 2 and level 2 but not after completion of level 1., Conclusion: Social contact with people with mental illness (rather than attending lectures about mental health) contributed significantly to the improvement in students' attitude towards depression and psychosis. With the positive preliminary results, the Mental Health Youth Ambassador Programme should be extended to more students., Competing Interests: AKY Chan was the Mental Health Youth Ambassador Taskforce Convener. TTY Yeung, JSC Xiong, and SKW Chan were Taskforce members. Other authors have no conflicts of interest to disclose.

Negative symptoms, particularly the motivation and pleasure (MAP) deficits, are associated with impaired social functioning in patients with schizophrenia (SCZ). However, previous studies seldom examined the role of the MAP on social functioning while accounting for the complex interplay between other psychopathology. This network analysis study examined the network structure and interrelationship between negative symptoms (at the "symptom-dimension" and "symptom-item" levels), other psychopathology and social functioning in a sample of 269 patients with SCZ. The psychopathological symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Positive and Negative Syndrome Scale (PANSS). Social functioning was evaluated using the Social and Occupational Functioning Assessment Scale (SOFAS). Centrality indices and relative importance of each node were estimated. The network structures between male and female participants were compared. Our resultant networks at both the "symptom-dimension" and the "symptom-item" levels suggested that the MAP factor/its individual items were closely related to social functioning in SCZ patients, after controlling for the complex interplay between other nodes. Relative importance analysis showed that MAP factor accounted for the largest proportion of variance of social functioning. This study is among the few which used network analysis and the CAINS to examine the interrelationship between negative symptoms and social functioning. Our findings supported the pivotal role of the MAP factor to determine SCZ patients' social functioning, and as a potential intervention target for improving functional outcomes of SCZ., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sarcopenia is a wild chronic disease among elderly people. Although it does not entail a life-threatening risk, it will increase the adverse risk due to the associated unsteady gait, fall, fractures, and functional disability. The import factors in diagnosing sarcopenia are muscle mass and strength. The examination of muscle mass must be carried in the clinic. However, the loss of muscle mass can be improved by rehabilitation that can be performed in non-medical environments. Electronic impedance myography (EIM) can measure some parameters of muscles that have the correlations with muscle mass and strength. The goal of this study is to use machine learning algorithms to estimate the total mass of thigh muscles (MoTM) with the parameters of EIM and body information. We explored the seven major muscles of lower limbs. The feature selection methods, including recursive feature elimination (RFE) and feature combination, were used to select the optimal features based on the ridge regression (RR) and support vector regression (SVR) models. The optimal features were the resistance of rectus femoris normalized by the thigh circumference, phase of tibialis anterior combined with the gender, and body information, height, and weight. There were 96 subjects involved in this study. The performances of estimating the MoTM used the regression coefficient ( r 2 ) and root-mean-square error (RMSE), which were 0.800 and 0.929, and 1.432 kg and 0.980 kg for RR and SVR models, respectively. Thus, the proposed method could have the potential to support people examining their muscle mass in non-medical environments.

Background: The variations in ABO blood groups are reported to be associated with multiple disorders, including ulcerative colitis (UC). We aimed to investigate the distribution of ABO blood groups in UC patients and explore its impact on disease severity., Methods: We retrospectively collected 129 UC patients diagnosed at our hospital between January 2000 and November 2019. Clinical characteristics, ABO blood groups, and operation rates were analyzed., Results: The mean diagnostic age of patients was 38.97 years. Males accounted for the majority of all patients (62.8%). Of 129 patients, 43 (33.3%) were blood type O, 41 (31.8%) were blood type A, 38 (29.5%) were blood type B, and 7 (5.4%) were blood type AB. Although our patients had higher ratio of blood type A comparing our general population, there was no statistically significant association of ABO blood types distribution between these two groups (p = 0.1906). In the subgroup analysis, there were no significant difference of disease locations and operation rates between different ABO blood groups. Furthermore, blood type A patients had higher serum hemoglobin (Hb) levels compared to blood type O patients (13.31 g/dL vs. 12.30 g/dL, p = 0.0347). Blood type A patients had lower serum erythrocyte sedimentation rate (ESR) levels compared to blood type O patients (12.46 mm/hour vs. 21.5 mm/hour, p = 0.0288). Blood type O had higher serum ESR levels compared to non-O groups (p = 0.0228). In the ABO blood groups and mean diagnostic age (≤ 40 years or > 40 years), there were no statistically significant difference between these two age groups, p = 0.5515., Conclusions: Our results showed ABO blood groups are not associated with UC in spite of a higher ratio of blood type A in our patients. Blood type O patients had higher serum ESR levels; however, blood type A patients had higher Hb levels., Competing Interests: The authors have declared that no competing interests exist.

Background: The earlier detection of dementia is needed as cases increase yearly in the aging populations of Taiwan and the world. In recent years, the global internet usage rate has gradually increased among older people. To expand dementia screening and provide timely medical intervention, a simple self-administrated assessment tool to assist in easily screening for dementia is needed., Objective: The two-part goal of this pilot study was, first, to develop a Game-Based Cognitive Assessment (GBCA) tool, and then, to evaluate its validity at early screening for patients with cognitive impairment., Method: The researchers recruited 67 patients with neurocognitive disorders (NCDs) and 57 healthy controls (HCs). Each participant underwent the GBCA and other clinical cognitive assessments (CDR, CASI, and MMSE), and filled out a questionnaire evaluating their experience of using the GBCA. Statistical analyses were used to measure the validity of the GBCA at screening for degenerative dementia., Results: The average GBCA scores of the HC and NCD groups were 87 (SD = 7.9) and 52 (SD = 21.7), respectively. The GBCA correlated well with the CASI (r2 = 0.90, p < 0.001) and with the MMSE (r2 = 0.92, p < 0.001), indicating concurrent validity. The GBCA cut-off of 75/76 corresponded to measurements of sensitivity, specificity, and area under curve of 85.1%, 91.5%, and 0.978, respectively. The positive predictive value was 91.9%, and the negative predictive value was 84.4%. The results of the user-experience questionnaire for the HC and NCD groups were good and acceptable, respectively., Conclusion: The GBCA is an effective and acceptable tool for screening for degenerative dementia.

Background: Electrical impedance tomography (EIT) can be used for continuous monitoring of pulmonary ventilation. However, no proper method has been developed for the separation of pulmonary ventilation and perfusion signals and the measurement of the associated ventilation/ perfusion (V/Q) ratio. Previously, various methods have been used to extract these components; however, these have not been able to effectively separate and validate cardiac- and pulmonary- related images., Aims: This study aims at validating and developing a novel method to separate cardiac- and pulmonary- related components based on the EIT simulation field of view and to simultaneously reconstruct the individual images instantly., Methods: Our approach combines the advantages of the principal component analysis (PCA) and processes that originally measure EIT data instead of handling a series of EIT images, thus introducing the empirical mode decomposition (EMD). The PCA template functions for cardiacrelated imaging and intrinsic mode functions (IMFs) of EMD for lung-related imaging are then adapted to input signals., Results: The proposed method enables the separation of cardiac- and lung-related components by adjusting the proportion of the key components related to lung imaging, which are the fourth component (PC4) and the first component (IMF1) in PCA- and EMD-based methods, respectively. The preliminary results on the application of the method to real human EIT data revealed the consistently better performance and optimal computation compared with previous methods., Conclusion: This study proposes a novel method for applying EIT to evaluate the best time of V/Q matching on the cardiovascular and respiratory systems; this aspect can be investigated in future research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aim: Meckel's diverticulum (MD) is a common congenital abnormality of the gastrointestinal (GI) tract. Although a few patients with MD present symptoms, preoperative diagnosis of MD is a clinical challenge because of its endoscopic inaccessibility. The aim of the present study was to investigate patients with MD diagnosed by double-balloon enteroscopy (DBE) in Taiwan., Methods: We conducted a retrospective study in a tertiary referral center in middle Taiwan. The clinical characteristics, endoscopic features, histopathological findings, treatment methods, and outcomes of patients with MD diagnosed by DBE were analyzed., Results: A total of 14 male patients with MD diagnosed by DBE were enrolled. The mean age of all patients was 32.3 years. GI bleeding (78.6%) accounted for the major indication of DBE, followed by abdominal pain and Crohn's disease follow-up. The mean distance between the ileocecal valve and MD was 68.9 cm. The average length of 12 patients with surgically resected MD was 5.2 cm. The diagnostic yields of the other modalities excepting DBE are as follows: capsule endoscopy, 50%; Meckel's scan, 11.1%; computed tomography, 16.7%; small bowel series, 0%; and angiography, 33.3%. MD presented as a large ostium in 13 patients (92.9%), a small ostium in 1 patient (7.1%), and bleeding signs in 10 patients (71.4%). Twelve patients (85.7%) underwent surgical treatment and 2 patients (14.3%) received conservative treatment. Heterotopic gastric tissue was identified in 4 patients (28.6%)., Conclusion: The present study showed that DBE is a more powerful modality in detecting MD than the other conventional modalities in Taiwan., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. It is characterized by massive tumor cell death leading to metabolic derangements and multiple organ failure. It is a rare complication of hepatocellular carcinoma (HCC) with only a few cases have been reported in the literature to date. We collected and summarized published case reports of tumor lysis syndrome in patients with HCC. We also reported one additional case who developed TLS after sorafenib therapy and wrote a clinical vignette. A comprehensive and current search for relevant articles was conducted in Medline and EMbase through May 2018. A systematic review was performed following the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).  A total of 28 cases of TLS associated with HCC were enrolled in our review. The median age of included cases was 55.5 years with a male to female ratio of 25:3. The two most common attributed factors of TLS were transcatheter arterial chemoembolization (TACE) (12 cases, 42.9 %) and sorafenib (nine cases, 32.1%). Among enrolled cases, the diameter of the largest tumor was 12 cm. Regarding Barcelona Clinic Liver Cancer (BCLC) staging, seven cases were at least stage A (22.6%), 11 cases were at least stage B (35.5%), and 10 cases were at least stage C (32.3%). The median time of onset of TLS was three days. As for uric acid-lowering agents, nine cases (32.1%) used allopurinol and four cases (14.3%) used rasburicase. Ten cases (35.7%) did not specify the medication prescribed. The overall mortality rate of this cohort was 67.9%. Compared with patients developing TLS following TACE, patients who had TLS following sorafenib therapy had a later onset of TLS (two days versus seven days, p < 0.001) and a more advanced stage of HCC (p = 0.002). There was a trend toward increased mortality of patients in the sorafenib group in comparison with those in the TACE group (77.8% versus 41.7%, p = 0.18). The results of this current review suggest that TLS rarely occurs in HCC but carries significantly higher mortality compared to TLS occurring in hematologic malignancies. It may occur shortly after TACE or with a delayed onset following sorafenib therapy. Considering the kaleidoscope of novel therapies and diverse pathogenesis of HCC, it is crucial for clinicians to recognize the clinicolaboratory derangements suggestive of TLS and initiate appropriate management. The present review highlights the need for clinicians to consider TLS within differentials when caring for patients with HCC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Chou et al.)

Objective: To illustrate the efficacy and safety profile of double-balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) using a short enteroscope in patients with surgically altered anatomy., Methods: A retrospective study was performed to review the endoscopic outcomes of patients undergoing DBE-assisted ERCP for biliary diseases in Tuen Mun and Pok Oi hospitals in Hong Kong SAR, China from December 2015 to December 2020., Results: Altogether 46 DBE-assisted ERCP procedures were performed in 37 patients. The enteroscopic success rate, defined as reaching the papilla or bilioenteric anastomosis, was 95.7% (95% confidence interval [CI] 85.2%-99.5%), which was significantly lower in patients with intact stomach than in those who had a previous gastrectomy (67% vs 100%, P = 0.014). The diagnostic ERCP success rate, defined as performance in an informative cholangiogram, was 84.1% (95% CI 69.9%-93.4%) in cases where it was attempted. Intended biliary therapeutic interventions were successfully performed in 76.1% (95% CI 61.2%-87.4%) of all procedures. Adverse events were reported in six (13.0%) procedures (95% CI 4.9%-26.3%), including the micro-perforation of the intestine in two (4.3%) patients with prior Roux-en-Y gastrectomy, three (6.5%) of acute cholangitis and one (2.2%) of acute pancreatitis. All adverse events were managed successfully using conservative methods except in one case of micro-perforation, which required a laparotomy., Conclusions: DBE-assisted ERCP using a short enteroscope is a promising technique for managing biliary diseases in patients with surgically altered anatomy. It must be performed to avoid perforation, particularly in patients with a Roux-en-Y reconstruction., (© 2021 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Visual and empirical assessments do not enable the early detection of wound deterioration or necroses. No suitable objective indicator for predicting poor wound-healing is currently available. We used infrared thermography to determine the association between wound temperature and pressure-wound healing. We examined patients with grades 2-4 pressure ulcers from a medical center in southern Taiwan and recorded the temperatures of the wound bed, periwound, and normal skin using infrared thermographic cameras. A total of 50 pressure ulcers and 248 infrared-thermography temperature records were analyzed. Normal skin temperature was not related to pressure ulcer wound healing. In a multivariate analysis, higher malnutrition universal-screening-tool scores were associated with poor wound-healing ( p = 0.020), and higher periwound-temperature values were associated with better wound-healing ( p = 0.028). In patients who had higher periwound-skin temperature than that of the wound bed, that result was also associated with better wound-healing ( p = 0.002). Wound-bed and periwound temperatures differed significantly with the grade of the pressure ulcer, and a high periwound temperature was positively correlated with wound healing. Infrared thermography can objectively serve as indicators for assessing pressure-ulcer healing.

Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fu, Cheng, Chen, Xu, Chen, Tian, Xu, Sun, Neoh, Dai, Han and Jin.)

Objective: Electrical impedance tomography (EIT) is a non-invasive technique that constitutes a promising tool for real-time imaging and long-term monitoring of the ventilation distribution at bedside. However, clinical monitoring and diagnostic evaluations depend on various methods to assess ventilation-dependent parameters useful for ventilation therapy. This study develops an automatic, robust, and rapidly accessible method for lung segmentation that can be used to define appropriate regions-of-interest (ROIs) within EIT images., Approach: To date, available methods for patients with defected lungs have the disadvantage of not being able to identify lung regions because of their poor ventilation responses. Furthermore, the challenges related to the identification of lung areas in EIT images are attributed to the low spatial resolution of EIT. In this study, a U-Net-based automatic lung segmentation model is used as a postprocessor to transform the original EIT image to a lung ROI image and refine the inherent conductivity distribution of the original EIT image. The trained U-Net network is capable of performing an automatic segmentation of conductivity changes in EIT images without requiring prior information., Main Results: The experimental design of this study was based on a finite element method (FEM) phantom used to assess the feasibility and effectiveness of the proposed method, and evaluation of the trained models on the test dataset was performed using the Dice similarity coefficient (DSC) and the mean absolute error (MAE). The FEM experimental results yielded values of 0.0065 for MAE, and values >0.99 for DSC in simulations., Significance: The use of a deep-learning-based approach attained automatic and convenient segmentation of lung ROIs into distinguishable images, which represents a direct benefit for regional lung ventilation-dependent parameter extraction and analysis. However, further investigations and validation are warranted in real human datasets with different physiology conditions with CT cross-section dataset to refine the suggested model.

Purpose . Work performance is closely related to one's attention level. In this study, a brain-computer interface (BCI) device suitable for office usage was chosen to quantify the individual's attention levels. Methods . A BCI system was adopted to interface brainwave signals to a coffee maker via three ascending levels of laser detectors. The preliminary test with this prototype was to characterize the attention level through the collected coffee amount. Here, the preliminary testing was comparing the correlation between the attention level and the participants' cumulative grade point average (CGPA) and scores from the 21-item depression, anxiety, and stress scale (DASS-21) and the attentional control scale (ACS) using ordinal regression. It was assumed that a greater CGPA would generate a greater attention level. Result . The generated coffee amount from the BCI system had a significant positive correlation with the CGPA ( p  = 0.004), mild depression ( p  = 0.019) and mild and extremely severe anxiety ( p  = 0.044 and p  = 0.019, respectively) and a negative correlation with the ACS score ( p  = 0.042). Conclusion . This simple and cost-effective prototype has the potential to enable everyone to know their immediate attention level and predict the possible correlation to their mental state.

Electrical impedance tomography (EIT) is widely used for bedside monitoring of lung ventilation status. Its goal is to reflect the internal conductivity changes and estimate the electrical properties of the tissues in the thorax. However, poor spatial resolution affects EIT image reconstruction to the extent that the heart and lung-related impedance images are barely distinguishable. Several studies have attempted to tackle this problem, and approaches based on decomposition of EIT images using linear transformations have been developed, and recently, U-Net has become a prominent architecture for semantic segmentation. In this paper, we propose a novel semi-Siamese U-Net specifically tailored for EIT application. It is based on the state-of-the-art U-Net, whose structure is modified and extended, forming shared encoder with parallel decoders and has multi-task weighted losses added to adapt to the individual separation tasks. The trained semi-Siamese U-Net model was evaluated with a test dataset, and the results were compared with those of the classical U-Net in terms of Dice similarity coefficient and mean absolute error. Results showed that compared with the classical U-Net, semi-Siamese U-Net exhibited performance improvements of 11.37% and 3.2% in Dice similarity coefficient, and 3.16% and 5.54% in mean absolute error, in terms of heart and lung-impedance image separation, respectively., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The positive end-expiratory pressure (PEEP) level with best respiratory system compliance (Crs) is frequently used for PEEP selection in acute respiratory distress syndrome (ARDS) patients. On occasion, two similar best Crs (where the difference between the Crs of two PEEP levels is < 1 ml/cm H 2 O) may be identified during decremental PEEP titration. Selecting PEEP under such conditions is challenging. The aim of this study was to provide supplementary rationale for PEEP selection by assessing the global and regional ventilation distributions between two PEEP levels in this situation., Methods: Eight ARDS cases with similar best Crs at two different PEEP levels were analyzed using examination-specific electrical impedance tomography (EIT) measures and airway stress index (SIaw). Five Crs were measured at PEEP values of 25 cm H 2 O (PEEP 25 ), 20 cm H 2 O (PEEP 20 ), 15 cm H 2 O (PEEP H ), 11 cm H 2 O (PEEP I ), and 7 cm H 2 O (PEEP L ). The higher PEEP value of the two PEEPs with similar best Crs was designated as PEEP upper , while the lower designated as PEEP lower ., Results: PEEP H and PEEP I shared the best Crs in two cases, while similar Crs was found at PEEP I and PEEP L in the remaining six cases. SIaw was higher with PEEP upper as compared to PEEP lower (1.06 ± 0.10 versus 0.99 ± 0.09, p = 0.05). Proportion of lung hyperdistension was significantly higher with PEEP upper than PEEP lower (7.0 ± 5.1% versus 0.3 ± 0.5%, p = 0.0002). In contrast, proportion of recruitable lung collapse was higher with PEEP lower than PEEP upper (18.6 ± 4.4% versus 5.9 ± 3.7%, p < 0.0001). Cyclic alveolar collapse and reopening during tidal breathing was higher at PEEP lower than PEEP upper (34.4 ± 19.3% versus 16.0 ± 9.1%, p = 0.046). The intratidal gas distribution (ITV) index was also significantly higher at PEEP lower than PEEP upper (2.6 ± 1.3 versus 1.8 ± 0.7, p = 0.042)., Conclusions: PEEP upper is a rational selection in ARDS cases with two similar best Crs. EIT provides additional information for the selection of PEEP in such circumstances., Supplementary Information: The online version contains supplementary material available at 10.1007/s40846-021-00668-2., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

A fully automated and accurate assay of rare cell phenotypes in densely-packed fluorescently-labeled liquid biopsy images remains elusive. Methods: Employing a hybrid artificial intelligence (AI) paradigm that combines traditional rule-based morphological manipulations with modern statistical machine learning, we deployed a next generation software, ALICE (Automated Liquid Biopsy Cell Enumerator) to identify and enumerate minute amounts of tumor cell phenotypes bestrewed in massive populations of leukocytes. As a code designed for futurity, ALICE is armed with internet of things (IOT) connectivity to promote pedagogy and continuing education and also, an advanced cybersecurity system to safeguard against digital attacks from malicious data tampering. Results: By combining robust principal component analysis, random forest classifier and cubic support vector machine, ALICE was able to detect synthetic, anomalous and tampered input images with an average recall and precision of 0.840 and 0.752, respectively. In terms of phenotyping enumeration, ALICE was able to enumerate various circulating tumor cell (CTC) phenotypes with a reliability ranging from 0.725 (substantial agreement) to 0.961 (almost perfect) as compared to human analysts. Further, two subpopulations of circulating hybrid cells (CHCs) were serendipitously discovered and labeled as CHC-1 (DAPI+/CD45+/E-cadherin+/vimentin-) and CHC-2 (DAPI+ /CD45+/E-cadherin+/vimentin+) in the peripheral blood of pancreatic cancer patients. CHC-1 was found to correlate with nodal staging and was able to classify lymph node metastasis with a sensitivity of 0.615 (95% CI: 0.374-0.898) and specificity of 1.000 (95% CI: 1.000-1.000). Conclusion: This study presented a machine-learning-augmented rule-based hybrid AI algorithm with enhanced cybersecurity and connectivity for the automatic and flexibly-adapting enumeration of cellular liquid biopsies. ALICE has the potential to be used in a clinical setting for an accurate and reliable enumeration of CTC phenotypes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Developed based on the Clinical Assessment Interview for Negative Symptoms (CAINS), the Motivation and Pleasure Scale-Self Report (MAP-SR) was designed to address the conceptual and psychometric limitations of other instruments assessing negative symptoms. We sought to validate and extend the applicability of the MAP-SR in the Chinese context across the schizophrenia spectrum., Methods: Three samples, including college students, individuals with social anhedonia and patients with schizophrenia, were recruited. Test-retest reliability, internal consistency, factor structure, and convergent/discriminant validity of the MAP-SR were examined. The group differences between the three participant groups were examined., Results: A four-factor structure of the MAP-SR was found consistently in all three groups of participants. The scale showed convergent/discriminant validity in patients with schizophrenia and individuals with social anhedonia, along with good reliability found in schizophrenia patients. The MAP-SR was also able to distinguish individuals with SocAnh and patients with SZ from matched controls., Conclusions: The MAP-SR is a valid and reliable instrument in assessing negative symptoms in individuals along the schizophrenia spectrum., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In a previous publication when we studied the purinergic receptor with which ATP interacted in mouse brain bEND.3 endothelial cells, we observed addition of 3 μm ARC 118925XX (ARC; selective P2Y 2 antagonist) strongly suppressed ATP-triggered Ca 2+ release, suggesting the response was mediated via P2Y 2 receptors. We here report ARC unexpectedly promoted substantial Ca 2+ influx even when ATP-triggered Ca 2+ release was largely inhibited. Since this large Ca 2+ influx may have important pharmacological significance, we proceeded to investigate its mechanism. ARC did not trigger intracellular Ca 2+ release thus suggesting Ca 2+ influx triggered by ARC was not store-operated. ARC-triggered Ca 2+ influx could be blocked by 1 mm Ni 2+ , a general Ca 2+ channel blocker, but not by SK&F 96365, a nonselective TRP channel blocker. Unexpectedly, ARC promoted influx of Na + and La 3+ , but not Mn 2+ . This is a surprising finding, since Mn 2+ is conventionally used as a Ca 2+ surrogate ion (as it permeates Ca 2+ channel), and La 3+ is classically used as a potent Ca 2+ channel antagonist. Electrophysiological examination showed ARC did not stimulate any cation currents. Therefore, ARC opened, rather than a cation channel pore, an unidentified Ca 2+ influx pathway which was Na + - and La 3+ -permeable but Mn 2+ -impermeable., (© 2019 Société Française de Pharmacologie et de Thérapeutique.)

Taiwan has a lower prevalence of inflammatory bowel disease (IBD) and a higher prevalence of tuberculosis (TB) infection than Western countries. The aim of this study was to investigate the prevalence of latent TB (LTB) and active TB infection in IBD patients treated with biological agents. From January 2000 to September 2018, we retrospectively collected data from IBD patients treated with biological agents at a tertiary referral center. Patients underwent a QuantiFERON-TB Gold test (QFT) to screen for TB infection before and after biological treatment courses. The diagnostic age, sex, body mass index, hepatitis B virus infection, biochemistry profile, treatment regimens, and the results of the QFT were analyzed. Overall, 130 IBD patients who received biological treatment were enrolled. The results of the QFT before biological treatment were determined in 120 patients (92%); of these, 10 were positive (8%), 110 were negative (85%), and 10 were indeterminate (9%). Six patients demonstrated seroconversion after biological treatment, as determined by the QFT. Three patients (2.4%) developed active pulmonary TB after biological treatment. In subgroup analysis, the positive QFT patients had a trend of lower baseline serum C-reactive protein and erythrocyte sedimentation rate levels than the negative QFT group. The present study demonstrates that the prevalence of LTB before and after biological treatment is higher in Taiwan than in most Western countries and similar to other Asian countries. Therefore, screening and monitoring of TB infection are necessary for IBD patients before and during biological treatments in Taiwan., Competing Interests: No conflicts of interest exist., (Copyright © 2019 Hsiang-Chun Lai et al.)

Background: The evaluation for surgical resectability of pancreatic ductal adenocarcinoma (PDAC) patients is not only imaging-based but highly subjective. An objective method is urgently needed. We report on the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of PDAC patients., Methods: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification., Findings: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC < 11.0 CTCs/2 ml was 16.5 months and for E-CTC ≥ 11.0 CTCs/2 ml was 5.5 months (HR = 0.050, 95% CI 0.004-0.578, P = .016). These OS results were consistent with the outcome of the metastatic analysis., Interpretation: Our work suggested that H-CTC is a better predictor of metastasis and E-CTC is a significant independent predictor of OS. The CTC phenotyping model has the potential to be developed into a reliable and accurate blood test for metastatic and OS assessments of PDAC patients. FUND: National Natural Science Foundation of China; Zhejiang Province Science and Technology Program; China Scholarship Council., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Ca 2+ -sensing receptors (CaSR) are G protein-coupled receptors which are activated by a rise in extracellular Ca 2+ . CaSR activation has been known to inhibit parathyroid hormone release and stimulate calcitonin release from parathyroid glands and thyroid parafollicular C cells, respectively. The roles of CaSR in other cell types including endothelial cells (EC) are much less understood. In this work, we demonstrated protein and functional expression of CaSR in mouse cerebral EC (bEND.3). Unexpectedly, CaSR response (high Ca 2+ -elicited cytosolic [Ca 2+ ] elevation) was unaffected by edelfosine or U73122 but strongly suppressed by SK&F 96365, ruthenium red, and 2-aminoethoxydiphenyl borate (2-APB), suggesting involvement of TRPV and TRPC channels but not Gq-phospholipase C. Acute application of NPS2143, a negative allosteric modulator of CaSR, suppressed CaSR response. However, a 40-min NPS2143 pre-treatment surprisingly enhanced CaSR response. After 4-24 h of application, this enhancement faded away and suppression of CaSR response was observed again. Similar results were obtained when La 3+ and Sr 2+ were used as CaSR agonists. The transient NPS 2143 enhancement effect was abolished by SB203580, a p38 inhibitor. Consistently, NPS 2143 triggered a transient p38 activation. Taken together, results suggest that in bEND.3 cells, NPS 2143 caused acute suppression of CaSR response, but then elicited a transient enhancement of CaSR response in a p38-dependent manner. NPS 2143 effects on CaSR in bEND.3 cells therefore depended on drug exposure time. These findings warrant cautious use of this agent as a CaSR modulator and potential cardiovascular drug.

The incidence and prevalence of inflammatory bowel disease (IBD) are low but increasing in Taiwan. We aimed to investigate the epidemiology and clinical outcomes of IBD in central Taiwan. We retrospectively analyzed patients with IBD diagnosed at our hospital between January 2000 and September 2018. The diagnostic criteria were based on endoscopic and pathologic findings. Clinical characteristics, treatment regimens, and treatment outcomes were analyzed. A total of 190 patients with IBD were enrolled (80 with Crohn's disease (CD) and 110 with ulcerative colitis (UC)). The mean age at diagnosis was 38.4 years (CD: 36 years, UC: 40 years). Male patients accounted for the majority of patients (71.1%). The male-to-female ratio was 3 : 1 for CD and 2.1 : 1 for UC. Current and ever smokers accounted for 30.5% of all patients. Only 4.2% of patients had a family history of IBD. Extraintestinal manifestations (EIMs) were reported in 7.9%, and colorectal cancers (CRCs) were reported in 2.1% of all patients. In patients with CD, the ileal type was the most common disease phenotype (57.5%), and the stricturing type was the most common disease behavior (60.0%). In patients with UC, left-sided colitis was the predominant disease extent (42.7%). The seroprevalence of hepatitis B virus (HBV) was 13.3%. The incidence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in patients with UC was 22%. 5-Aminosalicylic acids were the preferred treatment for UC, whereas corticosteroids, immunomodulators, and biologic agents were preferred for CD. In patients with CD, the bowel resection rate was 38.8%, and the incidence of hip avascular necrosis was 3.8%. In Taiwan, patients with IBD showed a male predominance, lack of familial clustering, a higher prevalence of HBV infection, and a lower prevalence of p-ANCA, EIMs, and CRC. Moreover, a higher incidence of the ileal type with poor outcomes of CD and left-sided predominance in UC were found.

In the western world, there is an increasing trend of occurrence in testicular cancer. Treatment of malignant testicular cancer is primarily combined surgery with various chemical drugs. Propofol has been frequently used as an anesthetic and sedative induction agent, which could modulate different γ‑aminobutyric acid receptors in the central nervous system. Studies demonstrated that propofol activates endoplasmic reticulum stress to induce apoptosis in lung cancer. However, it remains elusive whether propofol regulates caspase and/or mitogen‑activated protein kinase (MAPK) pathways to induce apoptosis in Leydig tumor cells. In the present study, MA‑10 mouse Leydig tumor cells were treated with propofol, and possible signal pathways associated with apoptosis were investigated. Results demonstrated that increasing dosage of propofol (300‑600 µM) for 24 h significantly decreased cell viability in MA‑10 cells (P<0.05). In flow cytometry analysis, the amount of sub‑G1 phase cell numbers in MA‑10 cells was significantly increased by propofol (P<0.05). Additionally, Annexin V/propidium iodide double staining further confirmed that propofol could induce MA‑10 cell apoptosis. Furthermore, cleaved caspase‑8, ‑9 and ‑3, and/or poly(ADP‑ribose) polymerase were significantly activated following treatment of propofol in MA‑10 cells. In addition, c‑Jun N‑terminal kinase, extracellular signal‑regulated kinase 1/2, and p38 were significantly activated by propofol in MA‑10 cells (P<0.05), indicating that propofol may induce apoptosis through the MAPK pathway. Additionally, propofol diminished the phosphorylation of Akt to activate apoptosis in MA‑10 cells. In conclusion, propofol may induce MA‑10 cell apoptosis by activating caspase and MAPK pathways, and inhibiting the Akt pathway in MA‑10 cells, demonstrating that propofol may be a potential anticancer agent against Leydig cell cancer.

ATP depletion induced by inhibiting glycolysis or mitochondrial ATP production has been demonstrated to cause cancer cell death. Whether ATP depletion can enhance the efficacy and potency of anti-cancer effects of herbal compounds is so far unknown. We examined the enhancing effect of ATP depletion on anti-cancer actions of tetrandrine (TET) in human lung carcinoma A549 cells. A 24-h incubation of A549 cells with tetrandrine caused a concentration-dependent cytotoxic effect (LC 50  = 66.1 μM). Co-incubation with 20 mM 2-deoxyglucose (2-DG, glycolysis inhibitor) caused only a very slight enhancement of tetrandrine cytotoxicity. By contrast, inhibiting mitochondrial ATP production with oligomycin (10 μM, ATP synthase inhibitor) and FCCP (30 μM, uncoupling agent) (thus, oligo-FCCP) on its own caused only slight cell cytotoxicity but strongly potentiated tetrandrine cytotoxicity (tetrandrine LC 50  = 15.6 μM). The stronger enhancing effect of oligo-FCCP than 2-DG on TET toxicity did not result from more severe overall ATP depletion, since both treatments caused a similar ATP level suppression. Neither oligo-FCCP nor 2-DG synergized with tetrandrine in decreasing mitochondrial membrane potential. TET on its own triggered reactive oxygen species (ROS) production, and oligo-FCCP, but not 2-DG, potentiated TET in causing ROS production. Taken together, our results suggest that inhibiting ATP production from mitochondria, but not from glycolysis, appears to be a very effective means in augmenting TET-triggered ROS production and hence toxicity in A549 cells.

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low-density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium-dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC-induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca 2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC-inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC-triggered Ca 2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC-induced caspase 3 activation and alleviate LPC-inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation., (© 2018 Société Française de Pharmacologie et de Thérapeutique.)

Background: In past magnetic resonance imaging studies, normal participants and schizophrenia patients have usually been compared using imaging processing modes with only one parameter. A more extensive evaluation of significant differences between gray and white matter in Schizophrenic patents was necessary., Methods: Voxel based morphometry was used to separate brain images into gray matter and white matter. Then, the images were mapped to Montreal Neurological Institute space, and DARTEL analytic template was applied for image calibration with statistical parametric mapping. Finally, joint independent component analysis was employed to analyze the gray and white matter of brain images from Schizophrenic patients and normal controls. In this study, joint independent component analysis was used to discriminate clinical differences in magnetic resonance imaging signals between Schizophrenic patients and normal controls., Results: Region of interest analyses has repeatedly shown gray matter reduction in the superior temporal gyrus of Schizophrenic patients., Conclusion: These results strongly support previous studies regarding brain volume in schizophrenic patients. The connection networks in frontal and temporal lobes evidently did not differ between normal participants and schizophrenia patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis. Voltage-gated K + (Kv) channels not only cause repolarization in excitable cells, but are also involved in multiple cellular functions in non-excitable cells. In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells., Methods: Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca 2+ . Cell migration was examined in the absence or presence of Kv channel blockers., Results: When compared with non-migratory cells, migratory cells had much higher Kv current densities, but rather unexpectedly, more depolarized membrane potential and reduced Ca 2+ influx. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv3.3, Kv3.4 and Kv4.3 channels. Cell migration was markedly inhibited by tetraethylammonium (TEA), a delayed rectifier Kv channel blocker, but not by 4-aminopyridine, an A-type Kv channel blocker., Conclusions: Taken together, our results show that increased Kv channel expression played a role in BT474 cell migration, and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis. The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Ca 2+ influx.

Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca 2+ signaling are hitherto unreported. In this report, we examined the effects of VA on agonist-triggered Ca 2+ signaling in mouse cortical bEND.3 EC. While VA (100 μm) did not cause an acute inhibition of ATP-triggered Ca 2+ signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca 2+ release; however, such treatment did not affect Ca 2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca 2+ pump, suggesting there was no reduction in Ca 2+ store size. VA-activated p38 signaling, and VA-induced inhibition of ATP-triggered Ca 2+ release was prevented by SB203580, a p38 inhibitor, suggesting VA caused the inhibition by activating p38. Remarkably, VA treatment did not affect acetylcholine-triggered Ca 2+ release, suggesting VA may not inhibit inositol 1,4,5-trisphosphate-induced Ca 2+ release per se, and may not act directly on Gq or phospholipase C. Taken together, our results suggest VA treatment, via a p38-dependent mechanism, led to an inhibition of purinergic receptor-effector coupling., (© 2018 Société Française de Pharmacologie et de Thérapeutique.)

Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti-cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca 2+ concentration ([Ca 2+ ] i ) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3 hour and 18 hour exposures, 10 µmol/L gossypol caused 23% and 65% cell death, respectively; 3 µmol/L gossypol caused no and 21% cell death, respectively. [Ca 2+ ] i was raised concentration-dependently by 1-10 µmol/L gossypol. We then explored the Ca 2+ signalling triggered by 3 µmol/L gossypol, which inflicted minimal toxicity: the Ca 2+ signal was composed largely of Ca 2+ influx and to a small extent, intracellular Ca 2+ release. Such Ca 2+ influx was much larger than store-operated Ca 2+ influx triggered by maximal Ca 2+ pool depletion. The Ca 2+ influx triggered by 3 and 10 µmol/L gossypol caused NO release and cell death, respectively. Gossypol also triggered influx of Mn 2+ and Na + , but not Ni 2+ and Co 2+ . Gossypol-triggered Ca 2+ signal was inhibited only by 14% and 37% by 100 µmol/L La 3+ and 10 µmol/L nimodipine, respectively; and not suppressed at all by 5 mmol/L Ni 2+ . Gossypol-triggered Ca 2+ signal was suppressed by 78% by 30 µmol/L ruthenium red, suggesting gossypol may act on TRPV channels. Our results suggest gossypol triggered opening of a non-selective cation pore, possibly a member of the TRPV family., (© 2018 John Wiley & Sons Australia, Ltd.)

The increasing incidence of bladder cancer and its high rate of recurrence over a 5-year period necessitate the need for diagnosis and surveillance amelioration. Cystoscopy and urinary cytology are the current tools, and molecular techniques such as BTA stat, NMP22, survivin mRNA, and urovysion FISH have attracted attention; however, they suffer from insufficient sensitivity or specificity. We developed a novel microfluidic approach for harvesting intact urinary-exfoliated tumor cells (UETC), either individually or in clusters, in a clean and segregated environment, which is crucial to minimize cross-contamination and misreads. To reliably and accurately identify UETC, our quantitative immunoassay involved concurrent use of two oncoproteins CK20 and CD44v6 antigen. CK20 is an intermediate filament protein overexpressed in urothelial tumors, and CD44v6 is a membrane adhesion molecule closely associated with cell invasion, tumor progression, and metastatic spread. Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. A total of 79 patients with bladder cancer and 43 age-matched normal controls (NC) were enrolled in the study. We detected considerably higher UETC counts in patients with bladder cancer versus the NC group [53.3 (10.7-1001.9) vs. 0.0 (0-3.0) UETCs/10 mL; P < 0.0001]. For bladder cancer detection, a stratified 10-fold cross-validation of training data reveals an overall predictive accuracy of 0.84 [95% confidence interval (CI), 0.76-0.93] with an 89.8% (95% CI, 71.5%-86.4%) for sensitivity and 71.5% (95% CI, 59.7%-83.3%) for specificity. Overall, the microfluidic immunoassay demonstrates increased sensitivity and specificity compared with other techniques for the detection of bladder cancer. Significance: A unique and promising diagnostic assay for bladder cancer is proposed with potential clinical utility as a complement for cytology. Cancer Res; 78(14); 4073-85. ©2018 AACR ., (©2018 American Association for Cancer Research.)