Simple detection of germline microsatellite instability for diagnosis of constitutional mismatch repair cancer syndrome.

Heterozygous mutations in DNA mismatch repair (MMR) genes result in predisposition to colorectal cancer (hereditary nonpolyposis colorectal cancer or Lynch syndrome). Patients with biallelic mutations in these genes, however, present earlier, with constitutional mismatch repair deficiency cancer syndrome (CMMRD), which is characterized by a spectrum of rare childhood malignancies and café-au-lait skin patches. The hallmark of MMR deficiency, microsatellite instability (MSI), is readily detectable in tumor DNA in Lynch syndrome, but is also present in constitutional DNA of CMMRD patients. However, detection of constitutional or germline MSI (gMSI) has hitherto relied on technically difficult assays that are not routinely applicable for clinical diagnosis. Consequently, we have developed a simple high-throughput screening methodology to detect gMSI in CMMRD patients based on the presence of stutter peaks flanking a dinucleotide repeat allele when amplified from patient blood DNA samples. Using the three different microsatellite markers, the gMSI ratio was determined in a cohort of normal individuals and 10 CMMRD patients, with biallelic germline mutations in PMS2 (seven patients), MSH2 (one patient), or MSH6 (two patients). Subjects with either PMS2 or MSH2 mutations were easily identified; however, this measure was not altered in patients with CMMRD due to MSH6 mutation.

Global Prevalence of Eating Disorders in Nutrition and Dietetic University Students: A Systematic Scoping Review.

BACKGROUND: Nutrition and dietetics (ND) training encourages behaviors that can be considered risk factors for eating disorders or disordered eating. This paper aims to explore the prevalence of eating disorders (EDs) and predictors of eating disorders (/P-EDs) in ND students. METHODS: A systematic scoping review of the literature was performed on PubMed, ERIC, PsychINFO, OVID Medline, and Scopus in October 2022. RESULTS: A total of 2097 papers were retrieved from the search, of which 19 studies met the inclusion criteria. The resultant literature reported that 4-32% of ND students were at high risk of EDs (n = 6 studies), and 23-89% could be classified as having orthorexia nervosa (n = 7 studies). Further, 37-86% reported body image/fat dissatisfaction (n = 10 studies), and 100% of students reported weight dissatisfaction (n = 1 study). CONCLUSIONS: This paper highlights the prevalence of EDs and P-EDs across ND students. Further research is warranted to explore the cause, context, and impact on ND students' wellbeing and professional identity and supporting diversity within the profession. Future studies should also consider curriculum approaches to address this occupational hazard.

Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ.

The transcription factor RUNX1 (AML-1, PEBP2alphaB and CBFA2) is essential for definitive haematopoiesis, and chromosomal translocations involving the RUNX1 gene are frequently found in acute leukaemias. The gene encoding the histone acetyltransferase MOZ is also rearranged in some acute leukaemias, resulting in the expression of MOZ fusion proteins. MOZ has recently been shown to interact directly with RUNX1, indicating that MOZ fusion proteins act by deregulating RUNX1 function. Macrophage inflammatory protein-1alpha (MIP-1alpha) is a proinflammatory cytokine that also inhibits proliferation of haematopoietic stem cells. Amongst the conserved sequence elements in the human MIP-1alpha promoter are two consensus RUNX sites. We have investigated the role of these RUNX sites in the regulation of the MIP-1alpha promoter by PMA/PHA stimulation in Jurkat T-cells. RUNX1 can specifically bind to both RUNX sites in vitro and chromatin immunoprecipitation assays demonstrated that endogenous RUNX1 is constitutively bound to the endogenous MIP-1alpha promoter. Mutation of the RUNX sites demonstrated that the proximal RUNX site is essential for PMA/PHA-stimulated activation of the MIP-1alpha promoter. Activation of the promoter can also be inhibited by heterologous expression of the repressor protein AML-1/ETO. We further demonstrate that MOZ can activate the MIP-1alpha promoter and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can synergistically activate the MIP-1alpha promoter. The regulation of MIP-1alpha expression by RUNX1/MOZ is discussed in the context of MIP-1alpha's role as an inhibitor of haematopoietic stem cell proliferation and its potential importance in leukaemias associated with RUNX1 or MOZ chromosomal rearrangements.