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.

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.

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.

Nucleophosmin 1, upregulated in adenomas and cancers of the colon, inhibits p53-mediated cellular senescence.

Dysregulation of nucleophosmin 1 (NPM1) has been found in numerous solid and hematological malignancies. Our previous meta-analysis of colorectal cancer (CRC) high throughput gene expression profiling studies identified it as a consistently reported up-regulated gene in the malignant state. Our aims were to compare NPM1 expression in normal colon, adenoma and CRC, to correlate their expressions with clinico-pathological parameters, and to assess the biological role of aberrant NPM1 expression in CRC cells. NPM1 transcript levels were studied in human CRC cell lines, whereas a tissue microarray of 57 normal human colon, 40 adenoma and 185 CRC samples were used to analyze NPM1 protein expression by immunohistochemistry. CRC cell lines were subjected to transient siRNA-mediated knockdown to study NPM1's roles on cell viability and senescence. NPM1 transcript levels were 7-11-folds higher in three different human CRC cell lines compared to normal colon cells. NPM1 protein expression was found to be progressively and significantly upregulated in CRC compared to adenomas and in adenomas compared to normal mucosa. Reducing NPM1 expression by siRNA had caused a significant decrease in cell viability, a concomitant increase in cellular senescence and cell cycle arrest. Cellular senescence induced under conditions of forced NPM1 suppression could be prevented by knocking down p53. The differential expression of NPM1 along the normal colon-adenoma-carcinoma progression and its involvement in resisting p53 related senescent growth arrest in CRC cell lines implicate its role in supporting CRC tumorigenesis.

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.

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.

Recurrent ectopic pancreatitis of the jejunum and mesentery over a 30-year period.

BACKGROUND: Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position, with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and confirmed on histological review of the resection. METHODS: A 67-year-old woman presented with clinical symptoms and biochemical evidence of pancreatitis. She had similar episodes over the past 30 years with unrevealing investigations, and was concluded to have idiopathic pancreatitis. She underwent CT and MRCP, with findings suggestive of ectopic pancreas, a diagnosis confirmed on histology of the resection. RESULTS: MRCP identified a mass in the proximal small bowel mesentery isointense to the native pancreas, with a small duct draining into a proximal jejunal loop. The resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans, an occasional ductular structure, and admixed areas of adipose tissue. The patient remained asymptomatic with normal biochemistry six months post-operatively. CONCLUSION: In an individual with abdominal pain, elevated serum amylase/lipase, but imaging findings of a normal native pancreas, ectopic pancreatitis should be considered, and can be evaluated by CT and MRCP.

Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis.

Our objective was to characterize the structural and metabolic changes of the corticospinal tract (CST) in ALS patients using combined diffusion tensor imaging (DTI) and magnetic resonance spectroscopic imaging (MRSI). Fourteen patients (male:female, 6:8; mean age, 54 years) and 14 controls (male:female, 8:6; mean age, 53 years) underwent imaging. Four regions of the CST were evaluated: precentral gyrus, corona radiata, posterior limb of the internal capsule, and cerebral peduncle. DTI and MRSI indices tested included fractional anisotropy (FA), apparent diffusion coefficient (ADC), and the ratio of N-acetylaspartate to choline (NAA/Cho) and creatine (NAA/Cr). In the precentral gyrus, NAA/Cho was reduced 18% (p<0.001), NAA/Cr was reduced 9% (p=0.01), and FA was reduced 3% (p=0.02). NAA/Cho and NAA/Cr were reduced in the corona radiata (p<0.001). Reduced NAA/Cho in the precentral gyrus correlated with shorter symptom duration (r=0.66, p=0.02) and faster disease progression (r=-0.65, p=0.008). Increased spasticity correlated with higher ADC in the precentral gyrus (R=0.52, p=0.005). In conclusion, both MRSI and DTI provided in vivo evidence of intracranial degeneration of the CST in ALS that was most prominent rostrally in the precentral gyrus.

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.

Spatial profiling of the corticospinal tract in amyotrophic lateral sclerosis using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) was used as a noninvasive method to evaluate the anatomy of the corticospinal tract (CST) and the pattern of its degeneration in amyotrophic lateral sclerosis (ALS). METHODS: Fourteen patients with ALS and 15 healthy controls underwent DTI. Parameters reflecting coherence of diffusion (fractional anisotropy, FA), bulk diffusion (apparent diffusion coefficient, ADC), and directionality of diffusion (eigenvalues) parallel to (lambda( parallel)) or perpendicular to (lambda( perpendicular)) fiber tracts were measured along the intracranial course of the CST. RESULTS: FA and lambda( parallel) increased, and ADC and lambda( perpendicular) decreased progressively from the corona radiata to the cerebral peduncle in all subjects. The most abnormal finding in patients with ALS was reduced FA in the cerebral peduncle contralateral to the side of the body with the most severe upper motor neuron signs. lambda( parallel) was increased in the corona radiata. Internal capsule FA correlated positively with symptom duration, and cerebral peduncle ADC positively with the Ashworth spasticity score. CONCLUSION: There is a spatial dependency of diffusion parameters along the CST in healthy individuals. Evidence of intracranial CST degeneration in ALS was found with distinct diffusion changes in the rostral and caudal regions.