Polycyclic aromatic hydrocarbons (PAHs) are commonly ingested via meat and are produced from high-temperature cooking of meat. Some of these PAHs have potential roles in carcinogenesis of colorectal cancer (CRC). We aimed to investigate PAH concentrations in eight types of commonly consumed ready-to-eat meat samples and their potential effects on gene expressions related to CRC. Extraction and clean-up of meat samples were performed using QuEChERS method, and PAHs were detected using GC-MS. Nine different PAHs were found in meat samples. Interestingly, roast turkey contained the highest total PAH content, followed by salami meat. Hams of varying levels of smokedness showed a proportional increase of phenanthrene (PHEN), anthracene (ANTH), and fluorene (FLU). Triple-smoked ham samples showed significantly higher levels of these PAHs compared to single-smoked ham. These three PAHs plus benzo[a]pyrene (B[a]P), being detected in three meat samples, were chosen as treatments to investigate in vitro gene expression changes in human colon cells. After PAH treatment, total RNA was extracted and rtPCR was performed, investigating gene expression related to CRC. B[a]P decreased mRNA expression of TP53. In addition, at high concentrations, B[a]P significantly increased KRAS expression. Treatments with 1 µM PHEN, 25 µM, and 10 µM FLU significantly increased KRAS mRNA expression in vitro, implying the potential basis for PAH-induced colorectal carcinogenesis. Opposingly, the ANTH treatment led to increased TP53 and APC expression and decreased KRAS expression, suggesting an anti-carcinogenic effect. To conclude, PAHs are common in ready-to-eat meat samples and are capable of significantly modifying the expression of key genes related to CRC.

Information regarding genetic alterations of driver cancer genes in circulating tumour cells (CTCs) and their surrounding immune microenvironment nowadays can be employed as a real-time monitoring platform for translational applications such as patient response to therapeutic targets, including immunotherapy. This study aimed to investigate the expression profiling of these genes along with immunotherapeutic target molecules in CTCs and peripheral blood mononuclear cells (PBMCs) in patients with colorectal carcinoma (CRC). Expression of p53, APC, KRAS, c-Myc, and immunotherapeutic target molecules PD-L1, CTLA-4, and CD47 in CTCs and PBMCs were analysed by qPCR. Their expression in high versus low CTC-positive patients with CRC was compared and clinicopathological correlations between these patient groups were analysed. CTCs were detected in 61% (38 of 62) of patients with CRC. The presence of higher numbers of CTCs was significantly correlated with advanced cancer stages (p = 0.045) and the subtypes of adenocarcinoma (conventional vs. mucinous, p = 0.019), while being weakly correlated with tumour size (p = 0.051). Patients with lower numbers of CTCs had higher expression of KRAS. Higher KRAS expression in CTCs was negatively correlated with tumour perforation (p = 0.029), lymph node status (p = 0.037), distant metastasis (p = 0.046) and overall staging (p = 0.004). CTLA-4 was highly expressed in both CTCs and PBMCs. In addition, CTLA-4 expression was positively correlated with KRAS (r = 0.6878, p = 0.002) in the enriched CTC fraction. Dysregulation of KRAS in CTCs might evade the immune system by altering the expression of CTLA-4, providing new insights into the selection of therapeutic targets at the onset of the disease. Monitoring CTCs counts, as well as gene expression profiling of PBMCs, can be helpful in predicting tumour progression, patient outcome and treatment.

Combination strategies of KRAS inhibition with immunotherapy in treating advanced or recurrent colorectal carcinoma (CRC) may need to be assessed in circulating tumour cells (CTCs) to achieve better clinical outcomes. This study aimed to investigate the genomic variations of KRAS in CTCs and matched CRC tissues and compared mRNA expression of KRAS and CTLA-4 between wild-type and KRAS-mutated CTCs and CRC tissues. Clinicopathological correlations were also compared. Six known mutations of KRAS were identified at both codon 12 and codon 13 (c.35G>T/G12V, c.35G>A7/G12D, c.35G>C/G12A, c.34G>A/G12S, c.38G>C/G13A, and c.38G>A/G13D). Three CTC samples harboured the identified mutations (16.7%; 3/18), while fifteen matched primary tumour tissues (65.2%, 15/23) showed the mutations. CTCs harbouring the KRAS variant were different from matched CRC tissue. All the mutations were heterozygous. Though insignificant, CTLA-4 mRNA expression was higher in patients carrying KRAS mutations. Patients harbouring KRAS mutations in CTCs were more likely to have poorly differentiated tumours (p = 0.039) and with lymph node metastasis (p = 0.027) and perineural invasion (p = 0.014). KRAS mutations in CTCs were also significantly correlated with overall pathological stages (p = 0.027). These findings imply the genetic basis of KRAS with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient’s disease.

Purpose: The aim of this scoping review was to explore current program evaluation practices across various medical schools. Methods: We conducted searches in MEDLINE (Ovid), Embase (Elsevier) and ERIC (ed.gov) for original research and review articles related to medical education evaluation with key words evaluation, program, medical education, pre-registration, framework, curriculum, outcomes, evaluation, quality. We followed Arksey and O’Malley’s (2005) process for scoping reviews. Results: Thirty-two articles were included. Studies were primarily concerned with either proving (n = 21) or improving efficacy of their programs (n = 11). No studies aimed at comparing programs. Nine were literature reviews. Others aimed to develop a new evaluation model (n = 7) or apply (n = 12) or validate (n = 4) an existing model (or part thereof). Twenty-two studies explicitly identified an evaluation model they had used or would recommend. Most frequently used models for evaluation were: Context-Input-Process-Product, Kirkpatrick, World Federation Medical Education, and the Standards by Joint Committee on Standards for Educational Evaluation. Overall, evaluations were learner-focused and accreditation driven with a minority considering the broader influences of program success. Conclusion: Program evaluation is fundamental to driving the quality of education delivered to produce workforce-ready healthcare professionals. The focus of current evaluations is on student experience and content delivery with a significant gap in the existing literature on evaluation related to staff, learner/staff well-being, equity, diversity, and meta evaluation.

To assess and compare the diagnostic performance of Clinical Prediction Rules (CPRs) developed to detect group A Beta-haemolytic streptococci in people with acute pharyngitis (or sore throat). A systematic review. We searched PubMed, Embase and Web of Science (inception-September 2022) for studies deriving and/or validating CPRs comprised of ≥2 predictors from an individual's history or physical examination. Two authors independently screened articles, extracted data and assessed risk of bias in included studies. A meta-analysis was not possible due to heterogeneity. Instead we compared the performance of CPRs when they were validated in the same study population (head-to-head comparisons). We used a modified grading of recommendations, assessment, development, and evaluations (GRADE) approach to assess certainty of the evidence. We included 63 studies, all judged at high risk of bias. Of 24 derived CPRs, 7 were externally validated (in 46 external validations). Five validation studies provided data for head-to-head comparison of four pairs of CPRs. Very low certainty evidence favoured the Centor CPR over the McIsaac (2 studies) and FeverPain CPRs (1 study) and found the Centor CPR was equivalent to the Walsh CPR (1 study). The AbuReesh and Steinhoff 2005 CPRs had a similar poor discriminative ability (1 study). Within and between study comparisons suggested the performance of the Centor CPR may be better in adults (>18 years). Very low certainty evidence suggests a better performance of the Centor CPR. When deciding about antibiotic prescribing for pharyngitis patients, involving patients in a shared decision making discussion about the likely benefits and harms, including antibiotic resistance, is recommended. Further research of higher rigour, which compares CPRs across multiple settings, is needed.