Genomic instability occurs in colorectal carcinomas but not in adenomas

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER⁺). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER⁺, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc.     

CSnrc: correlated sampling Monte Carlo calculations using EGSnrc

CSnrc, a new user-code for the EGSnrc Monte Carlo system is described. This user-code improves the efficiency when calculating ratios of doses from similar geometries. It uses a correlated sampling variance reduction technique. CSnrc is developed from an existing EGSnrc user-code CAVRZnrc and improves upon the correlated sampling algorithm used in an earlier version of the code written for the EGS4 Monte Carlo system. Improvements over the EGS4 version of the algorithm avoid repetition of sections of particle tracks. The new code includes a rectangular phantom geometry not available in other EGSnrc cylindrical codes. Comparison to CAVRZnrc shows gains in efficiency of up to a factor of 64 for a variety of test geometries when computing the ratio of doses to the cavity for two geometries. CSnrc is well suited to in-phantom calculations and is used to calculate the central electrode correction factor Pcel in high-energy photon and electron beams. Current dosimetry protocols base the value of Pcel on earlier Monte Carlo calculations. The current CSnrc calculations achieve 0.02% statistical uncertainties on Pcel, much lower than those previously published. The current values of Pcel compare well with the values used in dosimetry protocols for photon beams. For electrons beams, CSnrc calculations are reported at the reference depth used in recent protocols and show up to a 0.2% correction for a graphite electrode, a correction currently ignored by dosimetry protocols. The calculations show that for a 1 mm diameter aluminum central electrode, the correction factor differs somewhat from the values used in both the IAEA TRS-398 code of practice and the AAPM's TG-51 protocol.     

Blind evaluation of lymphocyte capping in Duchenne muscular dystrophy

Recently, Pickard et al reported decreased "capping" in lymphocytes from patients with Duchenne type muscular dystrophy (DMD) as well as female carriers of the DMD trait. To resolve subsequent debate about the reproducibility of this finding, we carried out a "blinded" collaborative study designed to eliminate the possibility of observer bias. Blood samples from DMD patients, their mothers, and controls were obtained and coded at Johns Hopkins and transported to the Medical College of Virginia, where lymphocyte capping was tested using FITC-labeled polyvalent anti-human immunoglobulin. Diminished capping in lymphocytes was found in 12 of 13 DMD patients (17 of 18 blood samples) and in 14 of 17 mothers of DMD patients (19 of 23 blood samples), as compared with 8 of 21 control subjects (8 of 22 blood samples). The results in both the patient and the carrier groups differed significantly from those in the control group, confirming previous observations of diminished lymphocyte capping in DMD. The findings provide support for the concept of a systemic defect associated with cell membranes in this disorder. The relatively high incidence of false positive results limits the usefulness of lymphocyte capping as a diagnostic test for carriers under the conditions of this study.     

Diet Quality and Cognitive Performance in Australian Adults Aged 55–85 Years: A Cross-Sectional Analysis of the Hunter Community Study Cohort

There is a lack of evidence to determine if diet quality is associated with cognitive performance in older adults. Therefore, the aim of this study was to examine whether diet quality is associated with cognitive performance among older adults. A cross-sectional, secondary analysis of baseline data from the Hunter Community Study (HCS), comparing diet quality, measured using the Australian Recommended Food Score (ARFS), along with validated cognitive performance instruments the Audio Recorded Cognitive Screen (ARCS) and the Mini-Mental State Examination (MMSE) were undertaken in adults aged 55–85 years, living in Newcastle, NSW, Australia. Adjusted linear regression analyses showed that, compared with the lowest ARFS quintile, those in the highest quintile had an ARCS score 5.883 units greater (p < 0.001; R² = 0.0098). Furthermore, when quintiles of ARFS score were tested against each ARCS sub-scale score, statistically significant associations were observed with the greatest effect for the Memory (β = 4.055; p = 0.001; R² = 0.0065) and Attention (β = 4.136; p = 0.002; R² = 0.0047) domains. No statistically significant associations were observed between quintiles of ARFS and MMSE score in the adjusted linear regression analyses. In conclusion, a positive association was observed between diet quality and cognitive performance within this sample of older Australian adults. Further investigation of the above association over time, when follow-up data becomes available, in longitudinal analysis is recommended.     

Intersecting stigma and HIV testing practices among urban refugee adolescents and youth in Kampala,Uganda: qualitative findings

IntroductionHIV‐related risks may be exacerbated in humanitarian contexts. Uganda hosts 1.3 million refugees, of which 60% are aged under 18. There are knowledge gaps regarding HIV testing facilitators and barriers, including HIV and intersecting stigmas, among urban refugee youth. In response, we explored experiences and perspectives towards HIV testing strategies, including HIV self‐testing, with urban refugee youth in Kampala, Uganda.MethodsWe implemented a qualitative study with refugee cisgender youth aged 16 to 24 living in Kampala''s informal settlements from February‐April 2019. We conducted five focus groups with refugee youth, including two with adolescent boys and young men, two with adolescent girls and young women and one with female sex workers. We also conducted five key informant (KI) interviews with government, non‐government and community refugee agencies and HIV service providers. We conducted thematic analyses to understand HIV testing experiences, perspectives and recommendations.ResultsParticipants (n = 49) included young men (n = 17) and young women (n = 27) originally from the Democratic Republic of Congo [DRC] (n = 29), Rwanda (n = 11), Burundi (n = 3) and Sudan (n = 1), in addition to five KI (gender: n = 3 women, n = 2 men; country of origin: n = 2 Rwanda, n = 2 Uganda, n = 1 DRC). Participant narratives revealed stigma drivers included fear of HIV infection; misinformation that HIV is a “Ugandan disease”; and blame and shame for sexual activity. Stigma facilitators included legal precarity regarding sex work, same‐sex practices and immigration status, alongside healthcare mistreatment and confidentiality concerns. Stigma experiences were attributed to the social devaluation of intersecting identities (sex work, youth, refugees, sexual minorities, people living with HIV, women). Participants expressed high interest in HIV self‐testing. They recommended HIV self‐testing implementation strategies to be peer supported and expressed concerns regarding sexual‐ and gender‐based violence with partner testing.ConclusionsIntersecting stigma rooted in fear, misinformation, blame and shame, legal precarity and healthcare mistreatment constrain current HIV testing strategies with urban refugee youth. Findings align with the Health Stigma and Discrimination Framework that conceptualizes stigma drivers and facilitators that devalue intersecting health conditions and social identities. Findings can inform multi‐level strategies to foster enabling HIV testing environments with urban refugee youth, including tackling intersecting stigma and leveraging refugee youth peer support.     

Development and usability of a feedback tool, “My Personal Brain Health Dashboard”, to improve setting of self-management goals among people living with HIV in Canada

Quality of Life Research - (1) To develop a personalized health outcome profile as a feedback tool to improve self-management in people living with chronic conditions such as HIV and (2) to...     

Protein tyrosine phosphatases

Protein tyrosine phosphatases (PTPases) balance the action of tyrosine kinases to maintain a set level of cellular tyrosine phosphorylation. Increases in tyrosine phosphorylation produced by transformation with constitutively active tyrosine kinases can initiate cellular proliferation. PTPases may act as tumor suppressors to counteract the transforming potential of oncogenic kinases. However, recent evidence suggests that PTPases have the potential to act as positive mediators of mitogenic signaling. If PTPases are acting as tumor suppressors, the expression of an inactive PTPase may cause an increase in overall tyrosine phosphorylation of cellular proteins, resulting in cellular transformation. Alternatively, overexpression of PTPases that play a positive role in signal transduction might also lead to proliferation. The role that each PTPase plays may depend in the cellular context in which it is expressed.