Identification of a novel NBN truncating mutation in a family with hereditary prostate cancer

Nibrin (NBN), located on chromosome 8q21 is a gene involved in DNA double-strand break repair that has been implicated in the rare autosomal recessive chromosomal instability syndrome known as Nijmegen Breakage Syndrome. NBS is characterized by specific physical characteristics (microcephaly and dysmorphic facies), immunodeficiency, and increased risk of malignancy. Individuals who are heterozygous for NBN mutations are clinically asymptomatic, but may display an elevated risk for certain cancers including, but not limited to, ovarian and prostate cancer as well as various lymphoid malignancies. In this study, 94 unrelated familial prostate cancer cases from the University of Michigan Prostate Cancer Genetics Project (n= 54) and Johns Hopkins University (n=40) were subjected to targeted next-generation sequencing of the exons, including UTRs, of NBN. One individual of European descent, diagnosed with prostate cancer at age 52, was identified to have a heterozygous 2117 C>G mutation in exon 14 of the gene, that results in a premature stop at codon 706 (S706X). Sequencing of germline DNA from additional male relatives showed partial co-segregation of the NBN S706X mutation with prostate cancer. This NBN mutation was not observed among 2768 unrelated European men (1859 with prostate cancer and 909 controls). NBN is involved in double-strand break repair as a component of the MRE11 (meiotic recombination 11)/RAD50/NBN genomic stability complex. The S706X mutation truncates the protein in a highly conserved region of NBN near the MRE11 binding site, thus suggesting a role for rare NBN mutations in prostate cancer susceptibility

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Improving accountability for equitable health and well-being in urban informal spaces: Moving from dominant to transformative approaches

This article critically reviews the literature on urban informality, inequity, health, well-being and accountability to identify key conceptual, methodological and empirical gaps in academic and policy discourses. We argue that critical attention to power dynamics is often a key missing element in these discourses and make the case for explicit attention to the operation of power throughout conceptualization, design and conduct of research in this space. We argue that: (a) urban informality reflects the exercise of power to confer and withhold advantage; (b) the dominant biomedical model of health poorly links embodied experiences and structural contexts; (c) existing models of accountability are inadequate in unequal, pluralistic governance and provision environments. We trace four conceptual and empirical directions for transformative approaches to power relations in urban health equity research

Food Fortification: The Level of Awareness among Kenyan Consumers

More than half of the morbidity and mortality cases among children in Kenya are as a result of micronutrient deficiencies (MNDs). Food fortification is considered by the Government of Kenya as a feasible strategy for addressing MNDs. Worldwide, fortification has been proven to be effective since it does not require any change in dietary habits. Success of large-scale food fortification however may depend on consumer awareness of the fortification benefits. A cross-sectional study was conducted in 13 counties to collect information on fortification awareness using structured questionnaires. 1435 respondents were selected using the Lot Quality Assurance Sampling method. Data were analyzed using Stata version 14.0 and statistical significance p<0.05. The study participants were described using descriptive statistics. The association of sociodemographic characteristics and awareness of fortification was performed using binary logistic regression analysis. The median age of the study participants was 35 years. Only 28% of the respondents were aware of the term “fortification.” Of the respondents, about 27% heard of food fortification through radio. Vernacular radio emerged as the most preferred channel for communicating fortification information among 24.9% of the respondents. Although awareness of vitamins (32%) and minerals (1.5%) was limited, most (76%) respondents reported of existence of health risks for lacking micronutrients. Awareness of food fortification was significantly associated with respondents’ occupation (p< 0.001), household size (p=0.012), education levels (p<0.001), and age (p=0.025). There is need for a wider use of broadcast media sources to modify information and education materials to promote fortification awareness among Kenyan consumers

Implications of COVID-19 for safeguarding in international development research: learning, action and reflection from a research hub

COVID-19 brings uncertainties and new precarities for communities and researchers, altering and amplifying relational vulnerabilities (vulnerabilities which emerge from relationships of unequal power and place those less powerful at risk of abuse and violence). Research approaches have changed too, with increasing use of remote data collection methods. These multiple changes necessitate new or adapted safeguarding responses. This practice piece shares practical learnings and resources on safeguarding from the Accountability for Informal Urban Equity hub, which uses participatory action research, aiming to catalyse change in approaches to enhancing accountability and improving the health and well-being of marginalised people living and working in informal urban spaces in Bangladesh, India, Kenya and Sierra Leone. We outline three new challenges that emerged in the context of the pandemic (1): exacerbated relational vulnerabilities and dilemmas for researchers in responding to increased reports of different forms of violence coupled with support services that were limited prior to the pandemic becoming barely functional or non-existent in some research sites, (2) the increased use of virtual and remote research methods, with implications for safeguarding and (3) new stress, anxiety and vulnerabilities experienced by researchers. We then outline our learning and recommended action points for addressing emerging challenges, linking practice to the mnemonic ‘the four Rs: recognise, respond, report, refer’. COVID-19 has intensified safeguarding risks. We stress the importance of communities, researchers and co-researchers engaging in dialogue and ongoing discussions of power and positionality, which are important to foster co-learning and co-production of safeguarding processes

Patterns of Human Plague in Uganda, 2008–2016

Plague is a highly virulent fleaborne zoonosis that occurs throughout many parts of the world; most suspected human cases are reported from resource-poor settings in sub-Saharan Africa. During 2008–2016, a combination of active surveillance and laboratory testing in the plague-endemic West Nile region of Uganda yielded 255 suspected human plague cases; approximately one third were laboratory confirmed by bacterial culture or serology. Although the mortality rate was 7% among suspected cases, it was 26% among persons with laboratory-confirmed plague. Reports of an unusual number of dead rats in a patient’s village around the time of illness onset was significantly associated with laboratory confirmation of plague. This descriptive summary of human plague in Uganda highlights the episodic nature of the disease, as well as the potential that, even in endemic areas, illnesses of other etiologies might be being mistaken for plague