PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study.

Background: Incipient tuberculosis, a progressive state of Mycobacterium tuberculosis infection with an increased risk of developing into tuberculosis disease, remains poorly characterised. Animal models suggest an association of progressive infection with bacteraemia. Circulating M tuberculosis DNA has previously been detected in pulmonary tuberculosis by use of Actiphage, a bacteriophage-based real-time PCR assay.

Optimization of Class I Histone Deacetylase PROTACs Reveals that HDAC1/2 Degradation is Critical to Induce Apoptosis and Cell Arrest in Cancer Cells.

Class I histone deacetylase (HDAC) enzymes 1, 2, and 3 organize chromatin as the catalytic subunits within seven distinct multiprotein corepressor complexes and are established drug targets. We report optimization studies of benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTACs) and for the first time describe transcriptome perturbations resulting from these degraders. By modifying the linker and VHL ligand, we identified PROTACs , , and with submicromolar DC values for HDAC1 and/or HDAC3 in HCT116 cells.

Using a Food Bank as a Platform for Educating Communities during the COVID-19 Pandemic.

Purpose: To describe a partnership between a public university and a regional foodbank aimed to promote health in food insecure communities, and to support nursing students' learning experiences in community health.

Design: A single setting case study.

Methods: A comprehensive health needs assessment conducted through a windshield survey and key informant interviews was used to identify the community's priorities.

Outrage and the emotional labour associated with environmental activism among nurses.

Aim: To investigate the emotions associated with environmental activism among nurses.

Background: Nursing has a long history of political activism in relation to social justice issues. Some nurses are environmental activists.

Becoming and being an environmentally 'woke' nurse: A phenomenological study.

Background: Increasing numbers of nurses view environmental activism as part of their role. No studies have explored the reasons.

Aim: This study aimed to identify what awakened and shaped US and UK nurses' environmental activism.

Preventable Injuries/Fatalities Due to Distracted Driving: A Call for a Coordinated Action.

In the past decade, distracted driving has emerged as one of the most prominent global road safety concerns. The singular and combined efforts of many organizations, such as Drop It And Drive (DIAD) and the Traffic Injury Research Foundation (TIRF), have identified the need for partnerships, shared information, and access to interpretable research findings to guide decision making and to identify effective strategies to reduce, if not eliminate, preventable injuries/fatalities from distracted driving, including whiplash-associated disorders. This editorial describes activities in 5 target areas identified in our environmental scan in Canada: (1) provincial/territorial government strategies, (2) enforcement, (3) data collection and measurement, (4) awareness campaigns, and (5) legislation.

Comet assay measures of DNA damage as biomarkers of irinotecan response in colorectal cancer in vitro and in vivo.

The use of irinotecan to treat metastatic colorectal cancer (CRC) is limited by unpredictable response and variable toxicity; however, no reliable clinical biomarkers are available. Here, we report a study to ascertain whether irinotecan-induced DNA damage measures are suitable/superior biomarkers of irinotecan effect. CRC-cell lines (HCT-116 and HT-29) were treated in vitro with irinotecan and peripheral blood lymphocytes (PBL) were isolated from patients before and after receiving irinotecan-based chemotherapy.

Grief and risk of depression in context: the emotional outcomes of bereaved cancer caregivers.

We investigated the relationships of grief and depression to cancer caregiving in early bereavement. We began with three expectations: (a) each outcome would reflect different situational predictors, (b) grief would be more directly related to such predictors, and (c) components of grief would relate differently to the caregiving context and depressed mood. We conducted telephone interviews with family caregivers of incurable cancer patients from two hospitals.

Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo.

Bladder cancer patients suffer significant treatment failure, including high rates of recurrence and poor outcomes for advanced disease. If mechanisms to improve tumour cell treatment sensitivity could be identified and/or if tumour response could be predicted, it should be possible to improve local-control and survival. Previously, we have shown that radiation-induced DNA damage, measured by alkaline Comet assay (ACA), correlates bladder cancer cell radiosensitivity in vitro.

Simplified method for the collection, storage, and comet assay analysis of DNA damage in whole blood.

Single-cell gel electrophoresis (comet assay) is one of the most common methods used to measure oxidatively damaged DNA in peripheral blood mononuclear cells (PBMC), as a biomarker of oxidative stress in vivo. However, storage, extraction, and assay workup of blood samples are associated with a risk of artifactual formation of damage. Previous reports using this approach to study DNA damage in PBMC have, for the most part, required the isolation of PBMC before immediate analysis or freezing in cryopreservative.

Relationships and emotional wellbeing among African American and White advanced cancer caregivers.

Objective: Advanced cancer family caregivers who have good relationships with other family members and with patient's health care providers (PHCPs) have less emotional distress than caregivers with poor relationships. Given a history of different experiences in medical settings among Whites and African Americans, we examined moderation effects by race.

Methods: Baseline data from an ongoing study were collected via telephone interviews with 397 family caregivers of advanced cancer patients at two cancer clinics.

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion.

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized.

Trepidation: a family member's response to shift change in the intensive care unit.

Every shift change in the intensive care unit presents an opportunity for uncertainty among family members regarding rules and information exchange. High levels of uncertainty maintain a presence in the intensive care unit environment, and feelings of trepidation can increase with uncertainty. Critical care nurses in the intensive care unit play a pivotal role in mediating family members' feelings of trepidation by what they do or do not do.

DNA strand breaks and hypoxia response inhibition mediate the radiosensitisation effect of nitric oxide donors on prostate cancer under varying oxygen conditions.

Prostate cancer cells can exist in a hypoxic microenvironment, causing radioresistance. Nitric oxide (NO) is a radiosensitiser of mammalian cells. NO-NSAIDs are a potential means of delivering NO to prostate cancer cells.

Primary care physicians' involvement in the cancer care of older long-term survivors.

Objective: This study investigated survivors' reports of primary care physicians' (PCPs) involvement in three key cancer survivorship activities: discussing cancer history, whether the PCP initiated discussions, and whether discussions led to tests/procedures.

Method: The sample included 215 older survivors whose health care was maintained in primary care. Logistic regression explored predictors of the three activities, including demographics, cancer characteristics, survivor/PCP association characteristics, health characteristics, and psychosocial well-being.

Protection of cells in physiological oxygen tensions against DNA damage-induced apoptosis.

Oxygen availability has important effects on cell physiology. Although hyperoxic and hypoxic stresses have been well characterized, little is known about cellular functions in the oxygen levels commonly found in vivo. Here, we show that p53-dependent apoptosis in response to different DNA-damaging agents was reduced when normal and cancer cells were cultured at physiological oxygen tensions instead of the usual atmospheric levels.

Predictors of engagement in a coping and communication support intervention for older patients with advanced cancer.

Objectives: To examine patterns and predictors of engagement in a coping and communication support (CCS) intervention tailored to the preferences of middle-aged and older patients in the early treatment phase for late-stage cancer.

Design: Randomized controlled trial examining processes and outcomes of a CCS intervention for patients with late-stage cancer over time.

Setting: Two ambulatory cancer clinics providing care for underserved populations in Cleveland.

Functioning of older, long-term cancer survivors: the role of cancer and comorbidities.

Objectives: To examine the relative effect of comorbidities, noncancer symptoms, and cancer-related factors on the functioning of older adult long-term survivors of breast, colorectal, and prostate cancers.

Design: Data from in-person interviews with survivors of a tumor registry-based stratified random sample were used to test a multivariate model using ordinary least-squares regression.

Setting: Survivors were identified in the tumor registry of a National Cancer Institute-designated Comprehensive Cancer Center in Cleveland, Ohio.

Health and well-being in older married female cancer survivors.

Objectives: To investigate differences between older married female cancer survivors and a matched comparison sample on physical health and on effects of health on depressive symptomatology.

Design And Setting: National survey data from the 1992 Health and Retirement Study.

Participants: Married women who reported having been diagnosed with cancer (N=245) and married women who did not report a cancer diagnosis but who matched the survivors on age, race, and ethnicity (N=245).

The restraint spiral: emergent themes in the perceptions of the physical restraint of juveniles.

This qualitative investigation explores the experiences of both children who were physically restrained in a juvenile facility and that of the adult professionals who restrained them. Among the major themes identified were the rationalizations of safety and noncompliance for restraint use by the adults. Children associated fear, anger, and retraumatization with the experience of being restrained.

DNA damage in earthworms from highly contaminated soils: assessing resistance to arsenic toxicity by use of the Comet assay.

Earthworms native to the former mine site of Devon Great Consols (DGC), UK reside in soils highly contaminated with arsenic (As). These earthworms are considered to have developed a resistance to As toxicity. The mechanisms underlying this resistance however, remain unclear.

Introducing a true internal standard for the Comet assay to minimize intra- and inter-experiment variability in measures of DNA damage and repair.

The Comet assay (CA) is a sensitive/simple measure of genotoxicity. However, many features of CA contribute variability. To minimize these, we have introduced internal standard materials consisting of 'reference' cells which have their DNA substituted with BrdU.

Patterns of adaptation in patients living long term with advanced cancer.

Background: With improved treatment, increasing proportions of patients with advanced cancer are surviving longer with their disease: into a second year after diagnosis and beyond. These longer term survivors face continuing challenges in selecting and shifting personal life goals and goals of care over years (rather than months) of life with incurable cancer. Studies are needed to explore adaptation over time in patients who are living longer term with late-stage cancer, including anxiety, depression, and spiritual well being, which are conceptualized as indicators of psychospiritual well being in patients with advanced cancer.

SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer.

The epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Two ZEB family members, ZEB1 and ZEB2(SIP1), inhibit transcription of the E-cadherin gene and induce EMT in vitro. However, their relevance to human cancer is insufficiently studied.