Temperament and adolescent suicide attempts: a case-control study with multi-ethnic Asian adolescents.

BACKGROUND: Suicide is the leading cause of death for adolescents in several parts of Asia, including Singapore. This study examines the relationship between temperament and youth suicide attempts in a sample of multi-ethnic Singaporean adolescents. METHODS: A case-control design compared 60 adolescents (Mage = 16.40, SDage = 2.00) with a recent suicide attempt (i.e., past 6 months) with 58 adolescents (Mage = 16.00, SDage = 1.68) without any history of suicide attempts. Presence of suicide attempts was established using the semi-structured interviewer-administered Columbia Suicide Severity Rating Scale. Participants also completed self-report measures on temperament traits, psychiatric diagnoses, stressful life events, and perceived parental rejection in an interview-based format. RESULTS: Psychiatric comorbidity, recent stressful life events, perceived parental rejection, and all five "difficult temperament" traits, were significantly overrepresented among adolescent cases relative to healthy controls. Adjusted logistic regression models revealed significant associations between suicide attempt, MDD comorbidity (OR: 10.7, 95% Cl: (2.24-51.39)), "negative mood" trait (OR: 1.12-1.18, 95% Cl: (1.00-1.27)), and the interaction term of "positive mood" and "high adaptability" traits (OR: 0.943 - 0.955, 95% Cl: (0.900 - 0.986)). Specifically, "positive mood" predicted lower likelihood of a suicide attempt when "adaptability" was high (OR: 0.335 - 0.342, 95% Cl: (0.186 - 0.500)) but not low (OR: 0.968 - 0.993, 95% Cl: (0.797 - 1.31)). CONCLUSION: Temperament screening may be important to identify adolescents at higher or lower risk of suicide at an early stage. More longitudinal and neurobiological research converging on these temperament findings will be helpful in ascertaining temperament screening as an effective suicide prevention methodology for adolescents.

Physical Activity and Nutrition Interventions for Type 1 Diabetes: A Meta-analysis.

BACKGROUND AND OBJECTIVES: Current evidence is lacking on physical activity and nutrition-based interventions focusing on the management of type 1 diabetes mellitus (T1DM) and health-related quality of life among children. To assess the effects of physical activity interventions and nutrition-based interventions for children with T1DM. METHODS: Data sources include the Cochrane Central Register of Controlled Trials, Medline, clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, CINAHL through January 2022. Study selection includes randomized controlled trials of children aged 18 years and below with T1DM comparing either a physical activity intervention, a nutrition-based intervention, or hybrid physical activity and nutrition-based intervention with placebo or no-treatment control. Data were pooled using a random-effects model. Primary outcomes were hemoglobin A1c (HbA1c), and health-related quality of life. RESULTS: Eighteen trials were included. Physical activity compared with the no-treatment group showed a lack of effect on HbA1c (mean difference = -0.58, 95% confidence interval -1.20 to 0.05; P value = .07). Nutrition-based intervention compared with no-treatment control for HbA1c level revealed a lack of effect (mean difference = -0.61, 95% confidence interval -1.48 to 0.26; P value = .17). Limitations include paucity of studies and low quality of evidence caused by the risk of bias. CONCLUSIONS: Despite the lack of significant evidence, the generally favorable results highlight the potential of such interventions in enhancing glycemic control and health-related quality of life. Additionally, promising results from a single physical activity-nutrition-based hybrid intervention in terms of glycemic control indicate the plausible effectiveness of a mixed intervention.

AI-doscopist: a real-time deep-learning-based algorithm for localising polyps in colonoscopy videos with edge computing devices.

We have designed a deep-learning model, an "Artificial Intelligent Endoscopist (a.k.a. AI-doscopist)", to localise colonic neoplasia during colonoscopy. This study aims to evaluate the agreement between endoscopists and AI-doscopist for colorectal neoplasm localisation. AI-doscopist was pre-trained by 1.2 million non-medical images and fine-tuned by 291,090 colonoscopy and non-medical images. The colonoscopy images were obtained from six databases, where the colonoscopy images were classified into 13 categories and the polyps' locations were marked image-by-image by the smallest bounding boxes. Seven categories of non-medical images, which were believed to share some common features with colorectal polyps, were downloaded from an online search engine. Written informed consent were obtained from 144 patients who underwent colonoscopy and their full colonoscopy videos were prospectively recorded for evaluation. A total of 128 suspicious lesions were resected or biopsied for histological confirmation. When evaluated image-by-image on the 144 full colonoscopies, the specificity of AI-doscopist was 93.3%. AI-doscopist were able to localise 124 out of 128 polyps (polyp-based sensitivity = 96.9%). Furthermore, after reviewing the suspected regions highlighted by AI-doscopist in a 102-patient cohort, an endoscopist has high confidence in recognizing four missed polyps in three patients who were not diagnosed with any lesion during their original colonoscopies. In summary, AI-doscopist can localise 96.9% of the polyps resected by the endoscopists. If AI-doscopist were to be used in real-time, it can potentially assist endoscopists in detecting one more patient with polyp in every 20-33 colonoscopies.

The interaction between SPARC and GRP78 interferes with ER stress signaling and potentiates apoptosis via PERK/eIF2α and IRE1α/XBP-1 in colorectal cancer.

Therapy-refractory disease is one of the main contributors of treatment failure in cancer. In colorectal cancer (CRC), SPARC can function as a sensitizer to conventional chemotherapy by enhancing apoptosis by interfering with the activity of Bcl-2. Here, we examine a novel mechanism by which SPARC further potentiates apoptosis via its modulation of the unfolded protein response (UPR). Using mass spectrometry to identify SPARC-associated proteins, GRP78 was identified as a protein partner for SPARC in CRC. In vitro studies conducted to assess the signaling events resulting from this interaction, included induction of ER stress with tunicamycin, 5-fluorouracil (5-FU), and irinotecan (CPT-11). We found that the interaction between GRP78 and SPARC increased during exposure to 5-FU, CPT-11, and tunicamycin, resulting in an attenuation of GRP78's inhibition of apoptosis. In addition, we also show that SPARC can sensitize CRC cells to PERK/eIF2α and IRE1α/XBP-1 UPR signaling by interfering with ER stress following binding to GRP78, which leads to ER stress-associated cell death in CRC cells. In line with these findings, a lower expression of GRP78 relative to SPARC in CRC is associated with a lower IC50 for 5-FU in either sensitive or therapy-refractory CRC cells. Interestingly, this observation correlates with tissue microarray analysis of 143 human CRC, where low GRP78 to SPARC expression level was prognostic of higher survival rate (P = 0.01) in individuals with CRC. This study demonstrates that modulation of UPR signaling by SPARC promotes ER stress-associated death and potentiates apoptosis. This may be an effective strategy that can be combined with current treatment options to improve therapeutic efficacy in CRC.

Adenoma detection rates in colonoscopies for positive fecal immunochemical tests versus direct screening colonoscopies.

BACKGROUND AND AIMS: Recent guidelines propose higher adenoma detection rate (ADR) benchmarks for colonoscopies performed for positive results for fecal immunochemical tests (FIT), but this is based on low-quality evidence. We aimed to compare ADR, advanced ADR (AADR), and number of adenomas per colonoscopy (APC) in direct screening colonoscopy (DSC) versus FIT-positive colonoscopy (FITC) in a multicenter Asia-Pacific cohort to justify differential targets. METHODS: Asymptomatic average-risk patients ≥50 years of age who underwent screening colonoscopy directly or as follow-up for positive OC-Sensor FIT results were identified from 8 sites across the Asia-Pacific region. Overall, sex-specific ADR, overall AADR, and overall APC were compared between the 2 screening methods. Multivariable logistic regression was performed to adjust for confounding by differences in patient characteristics. Linear regression was used to correlate ADR with APC and to propose APC benchmarks. RESULTS: A total of 2901 (mean age, 60.1 years; 57% men) individuals had DSC, and 2485 (mean age, 62.8 years; 57% men) underwent FITC. Overall ADR (53.6% vs 37.5%; odds ratio [OR], 1.93; P < .001), male-specific ADR (61.6% vs 44.6%; OR, 2; P < .001), female-specific ADR (43.2% vs 28.2%; OR, 1.94; P < .001) and overall AADR (29.9% vs 4.9%; OR, 8.2; P < .001) in FITC were significantly higher than the corresponding values for DSC. Differences remained significant after adjustment for patient characteristics. ADR was strongly and positively correlated to APC, with an ADR of 45% and 35% correlating to an APC of ∼1 and ∼0.65. CONCLUSIONS: Results from this international multicenter cohort study provide early evidence that newly proposed higher ADR targets are justified as quality indicators for FITC.

Lower Relative Contribution of Positive Family History to Colorectal Cancer Risk with Increasing Age: A Systematic Review and Meta-Analysis of 9.28 Million Individuals.

OBJECTIVES: Existing algorithms predicting the risk of colorectal cancer (CRC) assign a fixed score for family history of CRC. Whether the increased CRC risk attributed to family history of CRC was higher in younger patients remains inconclusive. We examined the risk of CRC associated with family history of CRC in first-degree relative (FDR) according to the age of index subjects (<40 vs. ≥40; <50 vs. ≥50; and <60 vs. ≥60 years). METHODS: Ovid Medline, EMBASE, and gray literature from the reference lists of all identified studies were searched from their inception to March 2017. We included case-control/cohort studies that investigated the relationship between family history of CRC in FDR and prevalence of CRC. Two reviewers independently selected articles according to the PRISMA guideline. A random effects meta-analysis pooled relative risks (RR). RESULTS: We analyzed 9.28 million subjects from 63 studies. A family history of CRC in FDR confers a higher risk of CRC (RR = 1.76, 95% CI = 1.57-1.97, p < 0.001). This increased risk was higher in younger individuals (RR = 3.29, 95% CI = 1.67-6.49 for <40 years versus RR = 1.42, 95% CI = 1.24-1.62 for ≥40 years, p = 0.017; RR = 2.81, 95% CI = 1.94-4.07 for <50 years versus RR = 1.47, 95% CI = 1.28-1.69 for ≥50 years, p = 0.001). No publication bias was identified, and the findings are robust in subgroup analyses. CONCLUSIONS: The increase in relative risk of CRC attributed to family history was found to be higher in younger individuals. Family history of CRC could be assigned a higher score for younger subjects in CRC risk prediction algorithms. Future studies should examine if such approach may improve their predictive capability.

Inactivation of the Kinase Domain of CDK10 Prevents Tumor Growth in a Preclinical Model of Colorectal Cancer, and Is Accompanied by Downregulation of Bcl-2.

Cyclin-dependent kinase 10 (CDK10), a CDC2-related kinase, is highly expressed in colorectal cancer. Its role in the pathogenesis of colorectal cancer is unknown. This study examines the function of CDK10 in colorectal cancer, and demonstrates its role in suppressing apoptosis and in promoting tumor growth in vitro and in vivo Modulation of CDK10 expression in colorectal cancer cell lines demonstrates that CDK10 promotes cell growth, reduces chemosensitivity and inhibits apoptosis by upregulating the expression of Bcl-2. This effect appears to depend on its kinase activity, as kinase-defective mutant colorectal cancer cell lines have an exaggerated apoptotic response and reduced proliferative capacity. In vivo, inhibiting CDK10 in colorectal cancer following intratumoral injections of lentivirus-mediated CDK10 siRNA in a patient-derived xenograft mouse model demonstrated its efficacy in suppressing tumor growth. Furthermore, using a tissue microarray of human colorectal cancer tissues, the potential for CDK10 to be a prognostic biomarker in colorectal cancer was explored. In tumors of individuals with colorectal cancer, high expression of CDK10 correlates with earlier relapse and shorter overall survival. The findings of this study indicate that CDK10 plays a role in the pathogenesis in colorectal cancer and may be a potential therapeutic target for treatment. Mol Cancer Ther; 16(10); 2292-303. ©2017 AACR.

Prevalence, distribution, and risk factor for colonic neoplasia in 1133 subjects aged 40-49 undergoing screening colonoscopy.

BACKGROUND AND AIM: Colorectal cancer (CRC) incidence is rising among <50-year olds. The objective of this study was to determine screening colonoscopy outcomes among 40- to 49-year olds, which are currently limited. METHODS: Asymptomatic 40- to 49-year olds underwent one time CRC screening colonoscopy at The Chinese University of Hong Kong between 2007 and 2011. Screening outcomes, including prevalence, distribution, and predictive factors for overall and specifically proximal colorectal neoplasia were determined. RESULTS: Among 1133 ethnic Chinese, colorectal neoplasia prevalence was 20.5%. In men, distal adenomas were associated with proximal colorectal neoplasia. Men, advancing age, a first degree relative (FDR) with CRC, and diabetes mellitus were independently associated with colorectal neoplasia. A colorectal neoplasia was three times more likely to be found in a 45- to 49-year-old man with FDR of CRC compared with a 40- to 44-year-old woman without a FDR of CRC. The numbers needed to screen one colorectal neoplasia, and one advanced neoplasm in the highest risk group of 45- to 49-year-old men with FDR with CRC were 2.8 (95% CI: 2.2-4.4) and 18.5 (95% CI: 8.9-39.2), respectively. CONCLUSIONS: Colorectal neoplasia prevalence in this 40- to 49-year-old Chinese cohort was higher than previous studies. Men, advancing age, FDR with CRC, and diabetes mellitus, can be used to risk stratify for neoplasia development. Men 45-49 years old with FDR with CRC represented the highest risk subgroup, with the lowest number needed to screen.

Endoscopic ultrasound of pancreatic lesions.

Endoscopic ultrasound (EUS) is a well-established tool for the evaluation of pancreatic lesions. Due to the closer proximity of EUS to the pancreas, EUS offers a high sensitivity for detection of small pancreatic mass and is the preferred modality for obtaining tissue for diagnosis of pancreatic mass. Contrast-enhanced EUS and/or elastography provide additional information to the fundamental B-mode ultrasound images, leading to more accurate diagnosis. The aim of this video-article is to show the different steps in performing EUS on pancreatic lesions and to provide some tips and tricks to improve and facilitate the execution of EUS on pancreatic lesions.

Pharmacological Treatment in Upper Gastrointestinal Bleeding.

Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency. Bleeding peptic ulcers account for the majority of causes in patients presenting with AUGIB, whereas variceal bleeding in cirrhotic patients represents a more severe form of bleeding. Endoscopic therapy is the mainstay of treatment in patients with active bleeding, as it achieves hemostasis and improves patient outcomes. Pharmacotherapy is an important adjunct to endoscopic hemostasis. In the management of patients with bleeding peptic ulcers, acid suppression after endoscopic hemostasis reduces rates of further bleeding and interventions. In patients with stable hemodynamics awaiting endoscopy, acid suppression starts ulcer healing and downstages stigmata of bleeding, thereby reducing the need for endoscopic therapy. In managing patients with variceal bleeding, early administration of vasoactive drugs lowers splanchnic blood flow, promotes hemostasis, and makes subsequent endoscopic treatment easier. The use of vasoactive agents and antibiotics have both been shown to reduce mortality. In this review article, strategies of acid suppression therapy for peptic ulcer bleeds, vasoactive agents, and antibiotics for variceal bleeding, together with recent evidence on the use of tranexamic acid in gastrointestinal bleeding, are discussed.

The educational environment: comparisons of the British and American postgraduate psychiatry training programmes in an Asian setting.

BACKGROUND: An American styled residency programme for postgraduate psychiatry training introduced in parallel with an existing British-styled programme in Singapore has proved challenging at various levels. AIMS: This study determined the educational environment of both programmes using the Postgraduate Hospital Educational Environment Measure (PHEEM) questionnaire. METHOD: All residents and trainees were invited to participate in this cross-sectional study with a self-administered PHEEM questionnaire. Statistical analysis was done using SPSS version 16. RESULTS: Trainees and residents perceived training as "more positive than negative with room for improvement." The subscale score for Teaching was lowest. Residents were dissatisfied with their new structured programme. Perceptions of clinical teachers were low in both training programmes. CONCLUSION: The existence of two programmes impacts the educational environment. Those involved in introducing revisions to educational programmes and curricula must attend to change management.