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Background: Clinician burnout is an important occupational hazard that may be exacerbated by the novel COVID-19 pandemic. Within Southeast Asia, burnout in gastroenterology is understudied. The primary objective of this study is to estimate the prevalence of burnout symptoms within gastroenterology, in member states of the Associations of Southeast Asian Nations (ASEAN), during and after the COVID-19 pandemic. The secondary objective is to identify work-related stressors that contribute to burnout in ASEAN gastroenterologists., Methods and Analysis: This is an observational study that will use anonymised online surveys to estimate the prevalence of burnout symptoms at two time points: during the COVID-19 pandemic in 2020 and in 2022 (assumed to be after the pandemic). Gastroenterologists from Singapore, Malaysia, Thailand, Indonesia, Philippines and Brunei will be invited to participate in the online survey through their national gastroenterology and endoscopy societies. Burnout will be assessed using the Maslach Burnout Inventory-Human Services Survey tool. Supplementary questions will collect demographic and qualitative data. Associations between demographic characteristics and burnout will be tested by multiple regression., Results: The prevalence of burnout symptoms in gastroenterology during the COVID-19 pandemic, and the baseline prevalence after COVID-19, will be established in the above-mentioned countries. Work-related stressors commonly associated with burnout will be identified, allowing the introduction of preventative measures to reduce burnout in the future., Ethics and Dissemination: Ethical approval was granted by the Singhealth Centralised Institutional Review Board (2020/2709). Results will be submitted for publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

Objective: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects., Design: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI)., Results: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie., Conclusion: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings., Competing Interests: Competing interests: DS receives research grants from Reckitt Benckiser UK, Jinshan Technology China and Alfa Sigma, Italy. SR: consulting Medtronic, research support Diversatek Healthcare, Medtronic; ES: Lecture Fee: Medtronic, Takeda, Janssen, MSD, Abbvie, Malesci; Consulting: Medtronic, Takeda, Janssen, MSD, Reckitt Bencikser, Sofar, Unifarco, SILA, Oftagest. CPG consults for Medtronic, Diversatek, Ironwood, IsoThrive and Quintiles., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Gemcitabine plus cisplatin (GC) remains the standard, frontline therapy for advanced biliary tract cancer (ABTC). The JCOG1113 study suggested that gemcitabine plus S-1 (GS) had noninferior median overall survival and comparable incidence of significant neutropenia as compared to GC treatments. This study evaluates the efficacy and safety of a modified GS regimen., Methods: The eligible patients with chemonaive, measurable ABTC received 800 mg/m 2 of gemcitabine on day 1 and 80 mg/m 2 /day of S-1 (80/100/120 mg for patients with body surface <1.25/ ≥1.25 and <1.5/ ≥1.5 m 2 respectively). The primary endpoint was the 12-week disease control rate (12-week DCR: objective response and stable disease ≥ 12 weeks). Per the p0 = 40% and p1 = 60% (α/β = 0.05/0.2) assumption, Simon's optimal two-stage design indicated 12-week DCR in ≥ 24 of 46 evaluable patients for significant activity. Tumour responses were assessed every 6 weeks., Results: Fifty-one patients were enrolled and most of them had intrahepatic cholangiocarcinoma (64.7%), metastatic disease (84.3%) and disease-related symptoms (82.4%). On intention-to-treat analysis, 11 (21.6%) patients showed partial response, whereas 21 (41.2%) showed stable disease ≥ 12 weeks. The progression-free and overall survival were 5.4 months (95% confidence interval [CI]: 3.5-7.0), and 12.7 months (95% CI: 6.1-15.6) respectively. The study met its primary endpoint with a 12-week DCR of 69.6% in 46 evaluable patients. Grade 3/4 treatment-related adverse eventsoccurred in < 6% of patients of all individual items. The mean dose intensities of S-1 and gemcitabine were 87.1% and 92.5% respectively., Conclusions: Modified GS showed moderate efficacy with a favourable safety profile in ABTC patients, thus mandating further assessment. ClinicalTrials.gov number: NCT02425137., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

By using a nationally representative school-based sample (4,816 children aged 8-14 years), we examined the risk of suicidality in children with elevated autistic traits and assessed the mediation of anxiety/depression and moderation effects of family function and academic performance. The Chinese version of the Social Responsiveness Scale (SRS-C) was used to measure autistic features. Logistic regression models were applied to assess associations between autistic traits and suicidality (suicidal ideation, suicide plans, and suicide attempts) for estimating the mediation effects of anxiety/depression and moderation effects of academic performance and family function after adjustment for control variables. Every 10-point increase in the SRS-C score was associated with a 1.3-1.4-fold increase in suicidality risk. Associations relating to suicide plans and attempts were fully mediated; however, the association with ideation was partially mediated by anxiety/depression. Academic performance and family function did not appear to moderate associations between autistic traits and suicidality. In conclusion, children with elevated autistic traits exhibited increased risk of suicidality, which could be generally attributed to symptoms of anxiety/depression. Because adequate family function and academic performance did not mitigate the link between elevated autistic traits and suicidality, in-depth exploration into specific protective factors in children with elevated autistic traits is warranted. LAY SUMMARY: By using a nationally representative school-based sample (4,816 children aged 8-14 years), we observed that the risk of suicidality increased in children with elevated autistic traits. This association was generally explained by increased levels of anxiety/depression. Furthermore, better family function and academic performance did not appear to mitigate the link between autistic traits and suicidality. Autism Res 2020, 13: 1811-1821. © 2020 International Society for Autism Research and Wiley Periodicals LLC., (© 2020 International Society for Autism Research, Wiley Periodicals, LLC.)

Background: The new coronavirus disease (COVID-19) has high infection and mortality rates, and has become a pandemic. The infection and mortality rates are lower in Asian countries than in European countries. This study aimed to conduct a survey on the effects of COVID-19 on the capacity to perform gastrointestinal motility tests in Asian countries compared with European countries., Methods: We used the questionnaire previously established by our team for researchers in European countries. The correlation between the decreased rate of gastrointestinal motility and function tests, and the infection/mortality rates of COVID-19 and stringency of a government's interventions in each country was analysed and protective measures were assessed., Results: In total, 58 gastroenterologists/motility experts in Asian countries responded to this survey. The infection/mortality rates of COVID-19 and Stringency Index had a significant impact on the testing capacity of oesophageal manometry and catheter-based pH monitoring. In European countries, most facilities used filtering facepiece 2/3 (FFP2/3) masks during oesophageal motility studies. Meanwhile, in Asian countries, most facilities used surgical masks., Conclusion: The total infection and mortality rates of COVID-19 can affect the rate of gastrointestinal motility testing and the type of protective equipment that must be used.

Background: In Malaysia, the problem of marital distress is fast becoming an important public health concern. A major shortcoming is inadequate marital evaluation. There are, however, very few localized instruments for married women in Malaysia. The objective of this study was to translate the original version of the Revised Dyadic Adjustment Scale (RDAS) and to evaluate for its psychometric properties. Multiple aspects of validity and reliability were also assessed., Materials and Methods: The questionnaire was first translated into the Malay language (RDAS-M). In this cross-sectional study, healthy married Malay women in Kota Bharu, Kelantan, were recruited from January to April 2018. Participants were asked to complete the RDAS-M that consists of three domains, that is, dyadic consensus, dyadic satisfaction, and dyadic cohesion with a total of 14 items. The concept, content, and construct validity using exploratory factor analysis (EFA) and reliability of the RDAS-M were assessed., Results: Of the 164 recruited participants, 150 consented to participate. The mean age of the participants was 34.1 years (standard deviation [SD], 9.5 years), ranging from 20 to 57 years. All 14 items were considered comprehensible by more than 95% of the subjects. Based on EFA, total variance extracted was 69.08%, and the original three factors were retained. The Malay version of the RDAS was valid based on factor loadings for dyadic consensus, dyadic satisfaction, and dyadic cohesion, which ranged from 0.64 to 0.80, 0.79 to 0.98, and 0.37 to 0.78, respectively. The internal consistency was good with coefficient α of 0.87 for dyadic consensus, 0.93 for dyadic satisfaction, and 0.78 for dyadic cohesion., Conclusions: The Malay version of the RDAS is easy to understand, and is a reliable and valid instrument for married women. It is also comparable with the original version of the RDAS in terms of structure and psychometric properties., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Pharmacy and Bioallied Sciences.)

Background: Despite the benefits and clinical necessity of insulin treatment in type 2 diabetes (T2D), healthcare providers are reluctant to initiate insulin, and patients are reluctant to start it for several reasons, one of these being the complexity of insulin treatment. Patients and their healthcare providers can benefit from titration algorithms (TAs) or rules that assist with the initiation and titration of insulin, performing the calculations that are needed to safely initiate and conservatively adjust., Methods: The primary objective for this in silico study was to examine the effectiveness of 3 dose TAs (1-3) for optimization of basal insulin glargine (Gla-100 and Gla-300). In the simulations, 100 virtual subjects with T2D were included (50% men, age 62 ± 3 years, HbA1c 8.1% ± 2.9%, body weight 94 ± 16 kg). Subjects were studied under each TA (TA1 and TA2 fasting blood glucose [FBG] targets 90-130 mg/dL, TA3 FBG target 110-150 mg/dL). Initial dose of both insulins was based on 0.2 U/kg body weight. During 3 months, subjects reported their FBG to the LTHome web-based dose guidance system with a rules engine to safely guide long-acting insulin titration and maintenance. Subjects followed dose recommendations to reach designated FBG target ranges., Results: All subjects reached stable doses under all TAs with both Gla-100 and Gla-300 insulin, and 93 or more of the 100 subjects, depending on the assigned TA, achieved the target FBG range within the 3-month simulation for all TAs. Mean FBG was lowered (Gla-100: 155 ± 40 to 118 ± 11 mg/dL with TA1 and TA2 and 132 ± 12 mg/dL for TA3; Gla-300: 125 ± 14 with TA1 and TA2 and 134 ± 15 mg/dL with TA3). Calculated HbA1c improved from 8.1% ± 2.9% to 7.1% ± 2.5% for TA1 and TA2 and 7.5% ± 2.5% for TA3, a reduction of 0.9% and 0.6% over 3 months for both insulins. Three subjects on Gla-100 and one subject on Gla-300 experienced mild hypoglycemia., Conclusion: All TAs delivered safe dose recommendations with minimal hypoglycemia, leading to a stable glucose control in the majority of subjects.

Globally, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly and constitutes a significant healthcare burden due to associated complications including hepatic (cirrhosis and hepatocellular cancer) and non-hepatic (cardiovascular deaths) disorders. It is closely linked to insulin resistance and metabolic syndrome but moderate alcohol consumption frequently coexists. Recently, genetic polymorphisms were implicated in the development of non-obese NAFLD. Apart from liver biopsy, in order to assess for steatosis, fibrosis and non-alcoholic steatohepatitis (NASH), advances in non-invasive serum tests and elastography have provided similarly accurate, more accessible and safer alternatives for risk stratification. As for treatment in 2020, weight loss and lifestyle modification remain the central strategy. Unfortunately, no pharmacological agents have been approved thus far, but there are a number of potential therapies in the pipeline for fibrosis and NASH. Treatment of underlying metabolic disorders is important. While the term NAFLD was coined in the 1980s, more recent understanding may support a change in nomenclature highlighting its strong metabolic roots., Competing Interests: No conflict of interests declared

Purpose: Suicide rates in South Korea have been one of the highest in the world. The aim of this study is to quantify the contributions of age, sex, method, and place of residence to the trends of the suicide rates between 2001 and 2016 in South Korea., Methods: Using the suicide data obtained from the South Korean National Death Registration data set for the years 2001-2016, a Joinpoint regression analysis was conducted to determine if there was a significant change in the trend of suicide rates. Next, a decomposition analysis method was used to quantify the contributions of age, sex, method, and places of residence to the changes in the suicide rates., Results: Suicide rates increased between 2001 and 2010, and decreased between 2010 and 2016. Among all the age groups, the 65-79 age group contributed most to the rise (18% in men and 7% in women) and fall (- 15% in men and - 14% in women) of suicide rates. Men contributed much more than women to the increasing trend of suicide rate (63.0% vs. 37.0%). Hanging was the key method of suicide, dominating the ups and downs of the suicide rates. The rates of suicide by pesticide poisoning have been decreasing since 2005 and suicide by charcoal burning continued to increase against a decreasing trend of suicide rate during the period of 2010-2016. The gap of the metropolitan-city-rural suicide rates was narrowing during the period under study, although the rural areas remained to have the highest suicide rates., Conclusion: The ups and downs of suicide rates in South Korea were not uniform across different sociodemographic groups. Age, sex, method, and place of residence contributed differently to the changes in suicide rates. Suicide prevention measures can be more focused on certain age-sex-method-region subgroups.

Background: It is unclear if the 99m Tc-sodium phytate ( 99m Tc-SP) is as reliable as the gold-standard 99m Tc-sulfur colloid ( 99m Tc-SC) for gastric emptying scintigraphy (GES). This study is aimed to compare the emptying rates of both radiotracers in a prospective, randomized cross-over trial and to determine the normative data of a healthy multi-ethnic Asian population., Methods: Out of the 44 healthy individuals screened, 31 (14 females; mean age: 28.4 ± 7.0 years) were enrolled and underwent GES using the standardized egg-white meal. All participants were randomly assigned to either 99m Tc-SP or 99m Tc-SC on the first GES session before crossed over to the other formulation after 2 weeks., Results: Both kits achieved the radiochemical purities of > 95%. The median rate (95th upper normative limit) of gastric emptying, reported as total gastric meal retention between 99m Tc-SP and 99m Tc-SC, was found to be comparable at all measured time points: 0.5 h [85.0% (96.6%) vs. 82.0% (94.0%)], 1 h [70.0% (86.4%) vs. 65.0% (86.6%)], 2 h [31.0% (55.8%) vs. 25.0% (64.4%)], 3 h [7.0% (26.3%) vs. 5.0% (29.9%)], and 4 h [3.0% (10.3%) vs. 2.0% (9.9%)]; P > 0.05. In addition, both radiotracers correlated well (Kendall's Tau (τ) coefficient = 0.498, P < 0.001) and presented with a good agreement at the 4th-hour time frame based on the Bland-Altman plot analysis., Conclusions: 99m Tc-SP is a valid radiotracer alternative to 99m Tc-SC for routine GES examination. The normative values for both radiotracers have also been determined for the healthy multi-ethnic Asian population., Trial Registration: This trial was registered retrospectively in the Thai Clinical Trials Registry on May 23rd, 2020 (Identifier: TCTR20200526004; http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=6296 ).

Background: Difficulties in prognostication are common deterrents to palliative care among dementia patients. This study aimed to evaluate the effectiveness of palliative care in reducing the extent of utilization of medical services and the potential risk factors of mortality among dementia patients receiving palliative care., Methods: We surveyed dementia patients involved in a palliative care program at a long-term care facility in Taipei, Taiwan. We enrolled 57 patients with advanced dementia (clinical dementia rating ≥ 5 or functional assessment staging test stage 7b). We then compared the extent of their utilization of medical services before and after the provision of palliative care. Based on multivariable logistic regression, we identified potential risk factors before and after the provision of palliative care associated with 6-month mortality., Results: The utilization of medical services was significantly lower among dementia patients after the provision of palliative care than before, including visits to medical departments (p < 0.001), medications prescribed (p < 0.001), frequency of hospitalization (p < 0.001), and visits to the emergency room (p < 0.001). Moreover, patients dying within 6 months after the palliative care program had a slightly but not significantly higher number of admissions before receiving hospice care (p = 0.058) on univariate analysis. However, no significant differences were observed in multivariate analysis., Conclusions: The provision of palliative care to dementia patients reduces the extent of utilization of medical services. However, further studies with larger patient cohorts are required to stratify the potential risk factors of mortality in this patient group.

During the Coronavirus Disease 2019 (COVID-19) pandemic, practices of gastrointestinal procedures within the digestive tract require special precautions due to the risk of contraction of severe acute respiratoy syndrome coronavirus-2 (SARS-CoV-2) infection. Many procedures in the gastrointestinal motility laboratory may be considered moderate to high-risk for viral transmission. Healthcare staff working in gastrointestinal motility laboratories are frequently exposed to splashes, air droplets, mucus, or saliva during the procedures. Moreover, some are aerosol-generating and thus have a high risk of viral transmission. There are multiple guidelines on the practices of gastrointestinal endoscopy during this pandemic. However, such guidelines are still lacking and urgently needed for the practice of gastrointestinal motility laboratories. Hence, the Asian Neurogastroenterology and Motility Association had organized a group of gastrointestinal motility experts and infectious disease specialists to produce a position statement paper based-on current available evidence and consensus opinion with aims to provide a clear guidance on the practices of gastrointestinal motility laboratories during the COVID-19 pandemic. This guideline covers a wide range of topics on gastrointestinal motility activities from scheduling a motility test, the precautions at different steps of the procedure to disinfection for the safety and well-being of the patients and the healthcare workers. These practices may vary in different countries depending on the stages of the pandemic, local or institutional policy, and the availability of healthcare resources. This guideline is useful when the transmission rate of SARS-CoV-2 is high. It may change rapidly depending on the situation of the epidemic and when new evidence becomes available.

A within-person diary research design with 39 full-time workers was used to examine the effects of daily cross-domain usage of information and communication technologies (ICTs) on job-related performance and stress in both workplace and home domains. Segmentation preference effects on links between cross-domain ICT usage and both job performance and job stress were also analyzed. A positive association was found for the first relationship in mixed home-workplace contexts, and a negative association for the second in home contexts only. A stronger segmentation preference effect on the negative relationship between cross-domain ICT usage and job stress was found for integrators (employees who integrate work and home domains) compared to separators (employees who separate work/non-work activities). Our findings suggest that daily cross-domain ICT usage can enhance job performance and reduce job stress, with a moderating effect of segmentation preference on the link between cross-domain ICT usage and job stress.

Background: Late-night supper increases the risk of postprandial reflux from the acid pocket especially in obesity. An alginate-based, raft-forming medication may be useful for obese patients with GERD., Aims: To compare the efficacy of Gaviscon Advance (Reckitt Benckiser, UK) and a non-alginate antacid in post-supper suppression of the acid pocket and post-prandial reflux among obese participants., Methods: Participants underwent 48 h wireless and probe-based pH-metry recording of the acid pocket and lower oesophagus, respectively, and were randomised to single post-supper (10 pm) dose of either Gaviscon Advance or a non-alginate antacid on the second night. Primary outcomes were suppression of median pH of acid pocket and lower oesophagus, measured every 10-minutes post-supper for 1 h. Secondary outcomes were suppression of % time pH < 4 at lower oesophagus and improvement in frequency and visual analogue score (VAS) of regurgitation., Results: Of the 81 screened participants, 55 were excluded and 26 (mean age 33.5 years, males 77.8% and BMI 32.8 kg/m 2 ) were randomised to Gaviscon Advance (n = 13) or antacid (n = 13). Median pH of the acid pocket but not the lower oesophagus was suppressed with Gaviscon Advance vs antacid (all P < 0.04) Gaviscon Advance but not antacid significantly reduced in % time pH < 4, symptom frequency and VAS on day 2 vs day 1 (all P < 0.05)., Conclusions: Among obese individuals, Gaviscon Advance was superior to a non-alginate antacid in post-supper suppression of the acid pocket. (Clinical trial registration unique identifier: NCT03516188)., (©2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Competing Interests: YYL is Associate Editor of the Journal of the Royal College of Physicians (JRCPE).

Liposomal irinotecan plus 5-fluorouracil/leucovorin (nal-IRI + 5-FU/LV) has shown to provide survival benefits for patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) in NAPOLI-1 trial, in which Asian patients experienced more hematological toxicity and subsequent dose modification. A retrospective chart review to investigate the administration pattern, therapeutic efficacy and safety profile of nal-IRI + 5-FU/LV in 44 consecutive patients with gemcitabine-refractory advanced PDAC treated between December 2016 and December 2018 in National Cheng Kung University Hospital, Taiwan. Most of them had metastatic diseases (88.6%), one-line of prior treatment (72.7%), ECOG PS 0-1 (72.7%) and starting dose of nal-IRI at 60 mg/m 2 (≈52 mg/m 2 irinotecan free-base) in 65.9%. The overall response rate was 9.1%. The median OS was 6.6 months for the entire cohort, and 7.8 and 2.7 months for patients of ECOG PS 0-1 and>2, respectively. The median OS of ECOG PS 0-1 patients with nal-IRI starting doses at 80 mg/m 2 (≈70 mg/m 2 irinotecan free-base, n = 13) and 60 mg/m 2 (n = 19) were 7.5 and 8.4 months, respectively. Thirty-four percent of patients experienced manageable grade 3-4 hematological toxicity. Our results confirm the clinical benefit of nal-IRI + 5-FU/LV for patients of gemcitabine-refractory advanced PDAC with good performance status in a real-world setting.

Tendons are hypocellular and hypovascular tissues, and thus, their natural healing capacity is low. In this study, we sought to evaluate the efficacy of platelet-rich fibrin (PRF) to serve as a bioactive scaffold in promoting the healing of rabbit Achilles tendon injury. For in vitro study, the essence portion of PRF was determined through bioluminescent assay. Furthermore, we analyzed the time-sequential cytokines-release kinetics of PRF and evaluated their effects on tenocytes proliferation and tenogenic gene expressions. In animal study, the rabbit Achilles tendon defect was left untreated or implanted with normal/heat-denatured PRF scaffolds. Six weeks postoperatively, the specimens were evaluated through sonographic imaging and histological analysis. The results revealed significantly more activated platelets on bottom half of the PRF scaffold. Cytokine concentrations released from PRF could be detected from the first hour to six days. For the in vitro study, PRF enhanced cell viability and collagen I, collagen III, tenomodulin, and tenascin gene expression compared to the standard culture medium. For in vivo study, sonographic images revealed significantly better tendon healing in the PRF group in terms of tissue echogenicity and homogeneity. The histological analysis showed that the healing tissues in the PRF group had more organized collagen fiber, less vascularity, and minimal cartilage formation. In conclusion, bioactive PRF promotes in vitro tenocytes viability and tenogenic phenotypic differentiation. Administration of a PRF scaffold at the tendon defect promotes tissue healing as evidenced by imaging and histological outcomes.

Background: Platelet-rich fibrin (PRF) is a bioactive biomaterial wherein cytokines are enmeshed within the interconnecting fibrin network. PRF can be fabricated into a patch to augment healing of the interface between a tendon graft and bone tunnel., Hypothesis: The bioactivity of a PRF scaffold is preserved after PRF is mechanically compressed into a patch. A bioactive PRF patch could promote the incorporation of a tendon graft within the bone tunnel through the formation of a tendon-bone healing zone composed of both fibrocartilaginous tissue and new bone., Study Design: Controlled laboratory study., Methods: Bioactivity of PRF was evaluated through treatment of rabbit tenocytes with PRF-conditioned medium and cultivation of cells on a PRF patch. Cellular morphologic features, viability, and differentiation were analyzed accordingly. In an animal study, a rabbit tendon-bone healing model was established through use of New Zealand White rabbits. The implanted tendon graft was enveloped circumferentially with a bioactive PRF patch before being pulled through a bone tunnel in the proximal tibia. Micro-computed tomography (micro-CT) imaging and histological and biomechanical analyses of the tendon-bone interface were performed at 12 weeks postoperatively., Results: PRF improved the viability of the cultured tenocytes. The effects of PRF on in vitro mineralization of tenocytes were comparable with the effects of standard culture medium. The gene expressions of type I collagen and osteopontin were upregulated upon PRF treatment. For the in vivo study, micro-CT images revealed significant new bone synthesis at the tendon-bone interface in the PRF-enveloped group. The tendon-bone healing zone was characterized by abundant fibrocartilage tissue and new bone formation as demonstrated by histological analysis. Biomechanical testing showed significantly higher ultimate loads in the PRF-enveloped group., Conclusion: Bioactive PRF could effectively augment healing of tendon graft to bone by inducing the formation of a transitional tendon-bone healing zone composed of fibrocartilage and bone., Clinical Relevance: Complete healing of the tendon graft in the bone tunnel is a prerequisite for successful ligament reconstruction, which would allow early and aggressive rehabilitation and rapid return to preinjury activity level. From a translational standpoint, the PRF-augmented healing in this rabbit animal model showed a promising biological approach to enhance tendon graft to bone healing via promotion of the functional anchorage between the 2 different materials.

Abdominal bloating (AB), a common complaint that affects quality of life and disturbs psychological well-being, is largely a behavioral-driven disorder. We aimed to develop and validate a new health belief of bloating (HB-Bloat) scale in the Malay language. The initial item pool was developed based on the theory of planned behavior, empirical literatures, expert review and in-depth interviews. Using the population with bloating (diagnosed based on the Rome IV criteria and pictogram), exploratory and confirmatory factor analytical approaches (EFA and CFA, respectively) were utilized to explore and confirm the domains in the new scale. There were 150 and 323 respondents in the EFA and CFA, respectively. There were 45 items in the initial scale, but it was reduced to 32 items after content validity and pre-testing. In EFA, 17 items with three (3) structure factors (attitude 4 items, subjective norm 7 items, and perceived behavior control 6 items) were identified. Total variance explained by the EFA model was 40.92%. The Cronbach alpha of the three (3) factors ranged from 0.61 to 0.79. With CFA, the three factors model was further tested. Five problematic items were identified and removed. The final measurement model fit the data well (root mean square error of approximation (RMSEA (90% CI) = 0.054 (0.038, 0.070), Comparative Fit Index (CFI) = 0.941, Tucker-Lewis Fit Index (TLI) = 0.924, and standardized root mean squared residual (SRMR) = 0.044). The construct reliability of the final measurement model ranged from 0.76 to 0.84. As a conclusion, the new HB-Bloat scale is a valid and reliable tool for assessment of health beliefs in bloating.

The KRAS mutations have been an obstacle to identify therapeutic targets in cancer treatment. In this work, we clarified the distinct metastasis pattern of non-small-cell lung carcinoma (NSCLC) induced by KRAS G12V /KRAS G12D mutations and inhibited the KRAS G12V mediated metastasis by Wnt inhibitor. First, we found that KRAS G12V induced more aggressive phenotype in vitro and in vivo experiments. The Gene Set Enrichment Analysis (GSEA) results of H838 KRAS G12V cells showed a significant negative correlation with RhoA-related signaling. Following this clue, we observed KRAS G12D induced higher activation of RhoA and suppressed activation of Wnt/β-catenin in H838KRAS G12D cells. The restored activation of Wnt/β-catenin in H838KRAS G12D cells could be detected when expression with a dominant-negative mutant of RhoA or treatment with RhoA inhibitor. Furthermore, the Wnt inhibitor abolished the KRAS G12V -induced migration. We elucidated the importance of the axis of RhoA/Wnt in regulatory NSCLC metastasis driven by KRAS mutations. Our data indicate that KRAS G12V driven NSCLC metastasis is Wnt-dependent and the mechanisms of NSCLC metastasis induced by KRAS G12V /KRAS G12D is distinct.

Background: Chronic constipation is a common symptom among the elderly, and it may affect their quality of life (QoL). A lack of available research focused on the elderly means that this effect is not well understood. This study aimed to develop and validate a new scale (Elderly-Constipation Impact Scale (E-CIS)) to measure the impact of chronic constipation on QoL among the elderly., Methods: A pool of items was generated from a qualitative study, literature reviews, and expert reviews. Exploratory factor analysis (EFA) was performed on the original 40 items of the E-CIS and followed by 27 items for confirmatory factor analysis (CFA). A total of 470 elderly people with chronic constipation were involved., Results: The mean age of the participants was 68.64 ± 6.57. Finally, only 22 items were indicated as appropriately representing the E-CIS, which were grouped into seven subscales: 'daily activities', 'treatment satisfaction', 'lack of control of bodily function', 'diet restriction', 'symptom intensity', 'anxiety' and 'preventive actions'. The scale was confirmed as valid (root mean square error of approximation (RMSEA) = 0.04, comparative fit index (CFI) = 0.961, Tucker-Lewis index (TLI) = 0.952 and chi-square/degree of freedom (chiSq/df) = 1.44) and reliable (Cronbach's alpha: 0.66-0.85, composite reliability (CR) = 0.699-0.851) to assess the impact of chronic constipation on the elderly's QoL., Conclusions: The E-CIS is useful to measure the impact of chronic constipation on the elderly's QoL. A further test is needed to determine the validity and reliability of this scale in other elderly population., Competing Interests: Yeong Yeh Lee is an Academic Editor for PeerJ., (©2020 Abdul Wahab et al.)

Competing Interests: No conflict of interests declared

Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action., (Copyright © 2020 Singh, Joshi, Tewari, Echeverría, Mocan, Sah, Parvanov, Tzvetkov, Ma, Lee, Poznański, Huminiecki, Sacharczuk, Jóźwik, Horbańczuk, Feder-Kubis and Atanasov.)

Background: Vasoactive drugs are frequently used in combination with endoscopic variceal ligation (EVL) in treatment of acute esophageal variceal bleeding (EVB). The aim of study was to assess physicians' preference of vasoactive agents in acute EVB, their reasons of preference and efficacy and safety of these short course regimens., Methods: Cirrhotic patients with suspected EVB were screened ( n  = 352). Eligible patients were assigned based on the physician's preference to either somatostatin (group S) or terlipressin (group T) followed by EVL. In group S, intravenous bolus (250 µg) of somatostatin followed by 250 µg/hour was continued for three days. In group T, 2 mg bolus injection of terlipressin was followed by 1 mg infusion every 6 h for three days., Results: A total of 150 patients were enrolled; 41 in group S and 109 in group T. Reasons for physician preference was convenience in administration (77.1%) for group T and good safety profile (73.2%) for group S. Very early rebleeding within 49-120 h occurred in one patient in groups S and T ( p  = 0.469). Four patients in group S and 14 patients in group T have variceal rebleeding episodes within 6-42 d ( p  = 0.781). Overall treatment-related adverse effects were compatible in groups S and T ( p  = 0.878), but the total cost of terlipressin and somatostatin differed i.e., USD 621.32 and USD 496.43 respectively., Conclusions: Terlipressin is the preferred vasoactive agent by physicians in our institution for acute EVB. Convenience in administration and safety profile are main considerations of physicians. Safety and hemostatic effects did not differ significantly between short-course somatostatin or terlipressin, although terlipressin is more expensive., Competing Interests: Lee Yeong Yeh is an Academic Editor for PeerJ., (©2019 Chuah et al.)

Barrett's esophagus (BE), a premalignant condition of the lower esophagus, is increasingly prevalent in Asia. However, endoscopic and histopathological criteria vary widely between studies across Asia, making it challenging to assess comparability between geographical regions. Furthermore, guidelines from various societies worldwide provide differing viewpoints and definitions, leading to diagnostic challenges that affect prognostication of the condition. In this review, the authors discuss the controversies surrounding the diagnosis of BE, particularly in Asia. Differences between guidelines worldwide are summarized with further discussion regarding various classifications of BE used, different definitions of gastroesophageal junction used across geographical regions and the clinical implications of intestinal metaplasia in the setting of BE. Although many guidelines recommend the Seattle protocol as the preferred approach regarding dysplasia surveillance in BE, some limitations exist, leading to poor adherence. Newer technologies, such as acetic acid-enhanced magnification endoscopy, narrow band imaging, Raman spectroscopy, molecular approaches and the use of artificial intelligence appear promising in addressing these problems, but further studies are required before implementation into routine clinical practice. The Asian Barrett's Consortium also outlines its ongoing plans to tackle the challenge of standardizing the diagnosis of BE in Asia., (© 2019 Japan Gastroenterological Endoscopy Society.)

Liver diseases form a heterogenous group of acute and chronic disorders of varying etiologies. Not only do they result in significant morbidity and mortality, but they also lead to a marked reduction in quality of life, together with a high socioeconomic burden globally. A better understanding of their global distribution is necessary to curb the massive health-care and socioeconomic burden that they entail. Notable differences and similarities have been described between common liver disease conditions occurring in Asia and the West (Europe and North America), giving rise to the need for an updated collective appraisal of this subject. In this review, the epidemiological differences of common liver conditions, specifically acute liver failure, drug-induced liver injury, acute-on-chronic liver failure, hepatocellular carcinoma, and non-alcoholic fatty liver disease, between Asia and the West are discussed., (© 2019 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Endoscopic, ultrasound-guided tissue acquisition (EUS-TA) with rapid on-site evaluation is recommended as a first choice in the diagnosis of pancreatic lesions. Since EUS facilities and rapid on-site evaluation are not widely available, even in medical centers, an alternative for precise diagnoses of pancreatic tumor is warranted. The percutaneous computed tomography-guided, core needle biopsy (CT-CNB) is a commonly applicable method for biopsies. Our institute has developed a fat-transversing approach for pancreatic biopsies which is able to approach most tumors in the pancreas without penetrating organs or vessels. Herein, we report a 15-year experiment of pancreatic tumor coaxial CT-CNB in 420 patients. The success rate of tissue yielding by the technique was 99.3%. The overall sensitivity, specificity, and accuracy were 93.2%, 100%, and 93.4%, respectively. The diagnostic accuracy could be increased to 96.4% in 2016-2018 (after the learning curve period). The overall complication rate was 8.6%. Neither life-threatening major complications, nor seeding through the biopsy tract, were observed. Our study supported the hypothesis that CT-CNB could be a complementary option for diagnostic tissue acquisition in patients with unresectable or metastatic pancreatic tumors when EUS-TA is either unsuitable or unavailable., Competing Interests: The authors declare no conflict of interest.

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. The current study aimed to determine the effectiveness and adherence of eight weeks of modified alternate-day calorie restriction (MACR) in the control of NAFLD activity. This was a randomized controlled trial with MACR as the intervention and normal habitual diet as control. The outcome measures were body mass index (BMI), blood lipids, fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasonographic measurements of liver steatosis and shear wave elastography (SWE). Per-protocol (PP) and intention-to-treat (ITT) analysis were performed within and between-groups with P < 0.05 as significant. 43 individuals with NAFLD satisfied study entry criteria, 33 were randomized to MACR and 10 to control group, and, 30 from MACR and 9 from control group completed PP. In between-group analysis of MACR vs. control, BMI were reduced in PP (P = 0.02) and ITT (P = 0.04). Only ALT was reduced in between-group analysis of MACR vs. control, both PP and ITT (P = 0.02 and 0.04 respectively). No reductions in all lipid parameters and FBS were found in between-group analyses (PP and ITT, all P > 0.22). Both liver steatosis grades and fibrosis (SWE) scores were reduced in between-group analyses of MACR vs. controls (PP and ITT, all P < 0.01). Adherence level remained between 75-83% throughout the study. As conclusion, 8 weeks of MACR protocol appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

Extensive studies have focused on selection mechanisms during visual search. One important influence on these mechanisms is the perceptual characteristics of the stimuli. We investigated the impact of perceptual similarity between targets and nontargets (T-N similarity) in a visual search task using EEG. Participants searched for a predefined target letter among five nontargets. The T-N similarity was manipulated with three levels: high, middle, and low. We tested for the influences of T-N similarity on an ERP (e.g., N2pc) and alpha oscillations. We observed a significant N2pc effect across all levels of similarity. The N2pc amplitude was reduced and occurred later for high similarity relative to low and middle similarities. We also showed that the N2pc amplitude was inversely correlated with the RTs across all similarities. Importantly, we found a significant alpha phase adjustment about the same time as the N2pc for high similarity; by contrast, no such effect was observed for middle and low similarities. Finally, we showed a positive correlation between the phase-locking value and the N2pc-the stronger the alpha phase-locking value, the larger the N2pc, when the T-N similarity was high. In conclusion, our results provide novel evidence for multiple competitive mechanisms during visual search.

Recent studies have realized the link between gut microbiota and human health and diseases. The question of diet, environment or gene is the determining factor for dominant microbiota and microbiota profile has not been fully resolved, for these comparative studies have been performed on populations of different ethnicities and in short-term intervention studies. Here, the Southern Chinese populations are compared, specifically the children of Guangzhou City (China), Penang City (west coast Malaysia) and Kelantan City (east coast Malaysia). These Chinese people have similar ancestry thus it would allow us to delineate the effect of diet and ethnicity on gut microbiota composition. For comparison, the Penang and Kelantan Malay children were also included. The results revealed that differences in microbiota genera within an ethnicity in different cities was due to differences in food type. Sharing the similar diet but different ethnicity in a city or different cities and living environment showed similar gut microbiota. The major gut microbiota (more than 1% total Operational Taxonomy Units, OTUs) of the children population are largely determined by diet but not ethnicity, environment, and lifestyle. Elucidating the link between diet and microbiota would facilitate the development of strategies to improve human health at a younger age.

Background: Expression of long non-coding RNAs (lncRNAs) has recently been recognized as a potential prognostic marker in acute myeloid leukemia (AML). However, it remains unclear whether incorporation of the lncRNAs expression in the 2017 European LeukemiaNet (ELN) risk classification can further improve the prognostic prediction., Methods: We enrolled 275 newly diagnosed non-M3 AML patients and randomly assigned them to the training (n = 183) and validation cohorts (n = 92). In the training cohort, we formulated a prognostic lncRNA scoring system composed of five lncRNAs with significant prognostic impact from the lncRNA expression profiling., Findings: Higher lncRNA scores were significantly associated with older age and adverse gene mutations. Further, the higher-score patients had shorter overall and disease-free survival than lower-score patients, which were also confirmed in both internal and external validation cohorts (TCGA database). The multivariate analyses revealed the lncRNA score was an independent prognosticator in AML, irrespective of the risk based on the 2017 ELN classification. Moreover, in the 2017 ELN intermediate-risk subgroup, lncRNA scoring system could well dichotomize the patients into two groups with distinct prognosis. Within the ELN intermediate-risk subgroup, we found that allogeneic hematopoietic stem cell transplantation could provide better outcome on patients with higher lncRNA scores. Through bioinformatics approach, we identified high lncRNA scores were correlated with leukemia/hematopoietic stem cell signatures., Interpretation: Incorporation of lncRNA scoring system in 2017 ELN classification can improve risk-stratification of AML patients and help clinical decision-making. FUND: This work was supported Ministry of Science and Technology, and Ministry of Health and Welfare of Taiwan., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

More than half of the world's population now lives in urban areas. Understanding the spatial distribution of suicide in these settings may inform prevention. Previous analyses of the spatial distribution of suicide in cities have largely been conducted in Western nations. We investigated the spatial pattern of suicide and factors associated with its spatial distribution in Taipei City, Taiwan. We estimated smoothed standardized mortality ratios for overall suicide and suicide by sex/age group across 432 neighborhoods (mean population size: 5500) in Taipei City (2004-2010) using Bayesian hierarchical models. A range of area-level characteristics including socioeconomic deprivation, social fragmentation, income inequality, and linking social capital were investigated for their associations with suicide mortality. Overall suicide rates were below average in the city center, whereas above average rates were found in some suburbs. The cartogram highlighted the concentration of suicide burden in one western area of the city. Male suicides demonstrated generally similar spatial patterning across age groups, while the geographic distribution of female suicides differed by age. After adjusting for other variables, two area characteristics were found to be associated with area suicide rates: the proportion of divorced/separated adults (rate ratio [RR] per one standard deviation increase = 1.08, 95% confidence interval 1.01-1.16), an indicator of social fragmentation; and median household income (RR = 0.80, 0.73-0.86), an indicator of socioeconomic deprivation. There was a 1.8-fold difference in suicide rates between neighborhood quintiles with the lowest and the highest median household income, with middle-aged males showing the largest gradient (3.2-fold difference). The geography of suicide in Taipei City showed spatial patterning and socioeconomic correlates distinct from cities in Western nations. There is a need for future research to better understand the correlates of change in the geographic distribution of suicide throughout the process of urban development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: To assess whether gender inequality determines the patterns of suicide gender ratios., Methods: Using suicide data obtained from the World Health Organization Statistical Information System, 2012, suicide gender ratios were calculated and a world map of the ratios constructed. Forest plots were utilized to assess whether gender inequality (indicated by the Gender Inequality Index ["GII"] and male to female sex ratios at birth) moderated the worldwide patterns of suicide gender ratios. Regression analyses were then performed to estimate the extent to which gender inequality affects suicide gender ratios before and after controlling for human development level ("HDI")., Results: Gradient relationships of suicide gender ratios across 3 tertiles of GII were observed (ratios = 2.03, 2.54, 3.51, respectively for high, moderate and low GII, P = 0.03). High sex ratio at birth was significantly associated with lower suicide gender ratio (ratio = 1.64 vs. 2.75, P = 0.00). Regression analyses showed that highest tertile of GII and high sex ratios at birth were significantly associated with lower suicide gender ratios (P = 0.00 and P = 0.00, respectively). When the level of human development level was controlled, high sex ratio at birth remained to be a significant determinant of suicide gender ratios (P = 0.00), whereas the significance of GII disappeared (P = 0.19)., Limitations: The cross-sectional data do not allow for causal inferences., Conclusions: Male to female suicide ratios were higher in countries with more egalitarian gender norms. Strategies to eliminate culturally embedded gender discrimination have the potentials to prevent suicides., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To explore the association between Attention-Deficit Hyperactivity Disorder ("ADHD") and suicidality in children. Mediating effects of family function and psychiatric co-morbidities were also explored., Methods: This is a national representative cross-sectional survey of school-based sample of 4739 children aged 7-15. Logistic regression was used to assess the excess risks of suicidality (i.e., suicidal ideation, suicide plan, and suicide attempts) in 412 children with ADHD. Serial multiple mediator models were conducted to assess the mediating effects of family function and psychiatric comorbidities., Results: The prevalence of suicidality in children with ADHD was approximately 20% in Taiwan. After adjusting for potential confounders, the risk of suicidality among children with ADHD was approximately four times higher than among non-ADHD children [(adjusted Odds Ratio ["OR"] = 3.82, 95% Confidence Interval ("CI") (2.73, 5.34)] for suicidal ideation, adjusted OR = 4.18, 95% CI (2.57, 6.80) for suicide plan and adjusted OR = 4.45, 95% CI (1.99, 9.93) for suicide attempts. The mediating effects of anxiety/depression and conduct problems were about 20% and 8%, respectively, across all suicide outcomes. The mediating effects of family function were around 6-7% for suicidal ideation and 16-18% for suicide plan and suicide attempts. The effects of ADHD on suicidality, in general, remained after considering the mediating roles of family function and psychiatric comorbid conditions., Conclusions: Children with ADHD are at a high risk of suicide. Although the family function and psychiatric co-morbidities partially mediate this association, ADHD in itself is a potent suicide risk factor and should be an important target for suicide prevention., (Copyright © 2018. Published by Elsevier B.V.)

Background: Gastroesophageal Reflux Disease Questionnaire (GERDQ) and Quality of Life in Reflux and Dyspepsia Questionnaire (QOLRAD) are reliable tools for evaluation of GERD., Aim: We aimed to test validity and reliability of Malay language translations of GERDQ and QOLRAD in a primary care setting., Methods: The questionnaires were first translated into the Malay language (GERDQ-M and QOLRAD-M). Patients from primary care clinics with suspected GERD were recruited to complete GERDQ-M, QOLRAD-M, and Malay-translated 36-item short-form health survey (SF-36 or SF-36-M), and underwent endoscopy and 24-h pH-impedance test., Results: A total of 104 (mean age 47.1 years, women 51.9%) participants were enrolled. The sensitivity and specificity for GERDQ-M cut-off score ≥8 were 90.2 and 77.4%, respectively. Based on this cut-off score, 54.7% had a high probability of GERD diagnosis. GERD-M score ≥8 vs. < 8 was associated with erosive esophagitis (p < 0.001), hiatus hernia (p = 0.03), greater DeMeester score (p = 0.001), and Zerbib scores for acid refluxes (p < 0.001) but not non-acid refluxes (p = 0.1). Mean total scores of QOLRAD-M and SF-36-M were correlated (r = 0.74, p < 0.001). GERDQ-M ≥8, erosive esophagitis, and DeMeester ≥14.72 were associated with impaired QOLRAD-M in all domains (all p < 0.02) but this was not seen with SF-36., Conclusions: GERDQ-M and QOLRAD-M are valid and reliable tools applicable in a primary care setting., (© 2018 S. Karger AG, Basel.)

Functional bowel disorders, including irritable bowel syndrome (IBS), are a chronic condition that can significantly reduce patients' quality of life. Therefore, this paper will review the roles of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polypols (FODMAP) diet in treating IBS, particularly in an Asian setting. About 20% of the general population is diagnosed with IBS. However, there are limited effective medical therapies available for treating IBS. Therefore, IBS presents a major challenge to the health-care providers. Recently, there is an increasing interest in the use of a diet low in FODMAP for the treatment of IBS. A low FODMAP diet can decrease the delivery of readily fermentable substrates to the small intestine and colon, thereby improving functional gastrointestinal symptoms.

Cognitive training and social engagement are two of the routes that potentially improve cognitive functions in older adults. The former targets specific functions so that an intervention can trigger the plasticity and efficiency of the underpinning neural systems, and the latter also provides an environment supportive of social and emotional needs. We investigated whether an integration of the two routes could enhance cognitive functions related to executive control, because no prior research has adopted a theory-driven approach to design a group-based cognitive training program for executive control. Forty-six healthy and active older adults living in community settings were randomly assigned to a group-based training program or a group-based active control program. Twenty-three volunteers in a community center were recruited for the waitlist control group. A battery of card games was designed for the cognitive training program based on three theoretical models of executive functions. A set of commercial board games were run in the active control program. Using untrained tests as the outcome measures, we found significant improvement on executive control in the cognitive training group compared with the active and waitlist control groups while the two control groups did not differ in performance. The cognitive training group did not outperform the two groups on a test of reasoning or on a test of delayed episodic memory. The results support the idea that cognitive training with social interaction can improve performance on untrained tests that share overlapping cognitive processes. Despite the inability to adapt to each person's performance, integrating the two routes is beneficial for improving cognitive functions in older adults.

Adverse childhood experiences (ACEs) and alcohol dependence (AD) carry independent risks for suicidal behavior. While the strength of the association between ACEs and attempted suicide is weakened following adjustment for AD, no study to date has directly been performed to determine whether AD affects the risk of suicide attributable to ACEs. The study aimed to examine the possible role of alcohol dependence (AD) in the relationship between various ACEs and attempted suicide. This cross-sectional study assessed history of ACEs among 184 AD patients and 205 control participants using the Family Health Questionnaire. Lifetime history of attempted suicide was collected using the Chinese version of the Composite International Diagnostic Interview. We used the Sobel test to examine the mediating effects of AD on the relationship between ACEs and attempted suicide. Results showed that the suicide attempters were associated with higher rates of AD and ACEs. The regression analysis showed that AD and multiple ACEs exposure are independently associated with attempted suicide. AD appears as a partial mediator in the relationship between attempted suicide and the specific type of ACE (exposure to a battered mother or sexual abuse) or exposure to ≥3 types of ACEs. We conclude that AD might partially mediate the associations detected between attempted suicide and exposure to a battered mother, sexual abuse, and ≥3 types of ACEs. These observations may provide important insight for intervention strategies aimed at reducing the risk of suicide attempts., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hyperalgesia is a common clinical phenomenon among opioid dependent patients on methadone maintenance therapy (MMT) and it may be associated with undertreated pain and/or therapeutic failure. This study aimed to investigate association between serum methadone concentration (SMC) and cold pressor pain responses. Cold pressor pain responses in 147 opioid dependent patients on MMT were assessed using cold pressor test (CPT) at 0 h and at 2, 4, 8, 12, and 24 h after the dose intake. Blood samples were collected at 24 h after the dose. Serum methadone concentrations were measured using the Methadone ELISA kit and classified into two categories: < 400 ng/mL and ≥ 400 ng/mL. Eighty-eight patients (59.9%) had trough concentrations of < 400 ng/mL and 40.1% had trough concentrations of ≥ 400 ng/mL. There were significant effects of SMC on the cold pressor pain threshold ( p = 0.019). Patients with concentrations < 400 ng/mL had significantly higher (almost 60% higher) cold pressor pain threshold (adjusted mean (95% CI) = 30.15 (24.29, 36.01) s) compared to those with concentrations of ≥ 400 ng/mL (18.93 (11.77, 26.08) seconds). There was also a 20% difference in pain tolerance, and 6% difference in cold pressor pain intensity score, neither of which were significant statistically ( p > 0.05). Our results suggest an association of trough methadone concentration with the cold pressor pain threshold among opioid dependent patients on MMT. It would be useful to study the mechanisms underlying this association to help managing pain in such a population.

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)