African-American patients with cancer Talking About Clinical Trials (TACT) with oncologists during consultations: evaluating the efficacy of tailored health messages in a randomised controlled trial—the TACT study protocol

Introduction Low rates of accrual of African-American (AA) patients with cancer to therapeutic clinical trials (CTs) represent a serious and modifiable racial disparity in healthcare that impedes the development of promising cancer therapies. Suboptimal physician–patient consultation communication is a barrier to the accrual of patients with cancer of any race, but communication difficulties are compounded with AA patients. Providing tailored health messages (THM) to AA patients and their physician about CTs has the potential to improve communication, lower barriers to accrual and ameliorate health disparities. Objective (1) Demonstrate the efficacy of THM to increase patient activation as measured by direct observation. (2) Demonstrate the efficacy of THM to improve patient outcomes associated with barriers to AA participation. (3) Explore associations among preconsultation levels of: (A) trust in medical researchers, (B) knowledge and attitudes towards CTs, (C) patient-family member congruence in decision-making, and (D) involvement/information preferences, and group assignment. Methods and analysis First, using established methods, we will develop THM materials. Second, the efficacy of the intervention is determined in a 2 by 2 factorial randomised controlled trial to test the effectiveness of (1) providing 357 AA patients with cancer with THM with 2 different ‘depths’ of tailoring and (2) either providing feedback to oncologists about the patients\u27 trial THM or not. The primary analysis compares patient engaged communication in 4 groups preconsultation and postconsultation. Ethics and dissemination This study was approved by the Virginia Commonwealth University Institutional Review Board. To facilitate use of the THM intervention in diverse settings, we will convene ‘user groups’ at 3 major US cancer centres. To facilitate dissemination, we will post all materials and the implementation guide in publicly available locations

Dextran sulfate enhances the level of an oxidative DNA damage biomarker, 8-oxo-7,8-dihydro-2'-deoxyguanosine, in rat colonic mucosa.

International audienceDextran sodium sulfate (DSS) given in drinking water can induce colonic inflammation and produce colorectal tumors in rodents, although it is not directly genotoxic. The hypothesis that DSS can produce free radicals and induce oxidative DNA damage in colonic mucosa has been tested. In rats fed for 2 days with water containing 3% and 6% DSS, colonic inflammation manifestations were recorded and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a major biomarker of oxidative DNA damage, was assayed in colonic mucosa. As compared with control rats given pure water, inflammatory manifestations were seen in rats given DSS. At the same time, 8-oxodGuo levels in colonic mucosa were doubled (P < 0.001). These results suggest that formation of oxidative DNA damage in colonic mucosa depends on inflammation and maybe on the production of reactive oxygen species. This study shows that DSS can induce oxidative DNA damage within only 2 days, which could explain in part its carcinogenic properties

Cloning, Expression and Purification of an Acetoacetyl CoA Thiolase from Sunflower Cotyledon

Thiolase I and II coexist as part of the glyoxysomal β-oxidation system in sunflower (Helianthus annuus L.) cotyledons, the only system shown to have both forms. The importance of thiolases can be underscored not only by their ubiquity, but also by their involvement in a wide variety of processes in plants, animals and bacteria. Here we describe the cloning, expression and purification of acetoacetyl CoA thiolase (AACT) in enzymatically active form. Use of the extensive amount of sequence information from the databases facilitated the efficient generation of the gene-specific primers used in the RACE protocols. The recombinant AACT (1233 bp) shares 75% similarity with other plant AACTs. Comparison of specific activity of this recombinant AACT to a previously reported enzyme purified from primary sunflower cotyledon tissue was very similar (263 nkat/mg protein vs 220 nkat/mg protein, respectively). Combining the most pure fractions from the affinity column, the enzyme was purified 88-fold with a 55% yield of the enzymatically active, 47 kDa AACT

The Black Feminist Mixtape: A Collective Black Feminist Autoethnography of Black Women\u27s Existence in the Academy

Seven Black women graduate students from across different functional areas of higher education work in solidarity to write a collective Black Feminist Autoethnography (BFA) (Griffin, 2012) about our experiences at our respective colleges and universities. BFA is a theoretical and methodological means for Black female academics to critically narrate the pride and pain of Black womanhood (Griffin, 2012, p. 1). This article centers Black feminist scholarship as a framework to reflexively interpret how we as seven Black women navigate within, against, and beyond the academy to address dominant narratives that affect our professional and personal experiences. We use contemporary music lyrics and poems by Black women to actively illustrate and interrogate our individual and collective positionalities to promote critical literacy. Together, we are seven Black sista scholars who reclaim our voice as legitimized epistemologies in academic spaces. Hear Our Voices

Reproducibility and sensitivity to change of various methods to measure joint space width in osteoarthritis of the hip: a double reading of three different radiographic views taken with a three-year interval

Joint space width (JSW) and narrowing (JSN) measurements on radiographs are currently the best way to assess disease severity or progression in hip osteoarthritis, yet we lack data regarding the most accurate and sensitive measurement technique. This study was conducted to determine the optimal radiograph and number of readers for measuring JSW and JSN. Fifty pairs of radiographs taken three years apart were obtained from patients included in a structure modification trial in hip osteoarthritis. Three radiographs were taken with the patient standing: pelvis, target hip anteroposterior (AP) and oblique views. Two trained readers, blinded to each other's findings, time sequence and treatment, each read the six radiographs gathered for each patient twice (time interval ≥15 days), using a 0.1 mm graduated magnifying glass. Radiographs were randomly coded for each reading. The interobserver and intraobserver cross-sectional (M0 and M36) and longitudinal (M0–M36) reproducibilities were assessed using the intraclass coefficient (ICC) and Bland–Altman method for readers 1 and 2 and their mean. Sensitivity to change was estimated using the standardized response mean (SRM = change/standard deviation of change) for M0–M36 changes. For interobserver reliability on M0–M36 changes, the ICCs (95% confidence interval [CI]) were 0.79 (0.65–0.88) for pelvic view, 0.87 (0.78–0.93) for hip AP view and 0.86 (0.76–0.92) for oblique view. Intraobserver reliability ICCs were 0.81 (0.69–0.89) for observer 1 and 0.97 (0.95–0.98) for observer 2 for the pelvic view; 0.87 (0.78–0.92) and 0.97 (0.96–0.99) for the hip AP view; and 0.73 (0.57–0.84) and 0.93 (0.88–0.96) for the oblique view. SRMs were 0.61 (observer 1) and 0.82 (observer 2) for pelvic view; 0.64 and 0.75 for hip AP view; and 0.77 and 0.70 for oblique view. All three views yielded accurate JSW and JSN. According to the best reader, the pelvic view performed slightly better. Both readers exhibited high precision, with SRMs of 0.6 or greater for assessing JSN over three years. Selecting a single reader was the most accurate method, with 0.3 mm precision. Using this cutoff, 50% of patients were classified as 'progressors'

Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning

Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids

A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the oxidized bases including 8-oxo-7,8-dihydroguanine (8-oxoGua), a ubiquitous marker of almost every type of oxidative stress in cells. Efforts to standardize the nomenclature and abbreviations of the main DNA degradation products that arise from oxidative pathways are reported. Information is also provided on the main oxidative radicals, non-radical oxygen species, one-electron agents and enzymes involved in DNA degradation pathways as well in their targets and reactivity. A brief classification of oxidatively generated damage to DNA that may involve single modifications, tandem base modifications, intrastrand and interstrand cross-links together with DNA-protein cross-links and base adducts arising from the addition of lipid peroxides breakdown products is also included

Chronic methamphetamine effects on brain structure and function in rats

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity

Use of Oral Cholera Vaccine in Haiti: A Rural Demonstration Project

A cholera epidemic has claimed the lives of more than 8,000 Haitians and sickened 650,000 since the outbreak began in October 2010. Early intervention in the epidemic focused on case-finding, treatment, and water and sanitation interventions for prevention of transmission. Use of oral cholera vaccine (OCV) as part of a complementary set of control activities was considered but initially rejected by policymakers. In December 2011, the Minister of Health of Haiti called for a demonstration of the acceptability and feasibility of the use of OCV in urban and rural Haiti. This paper describes the collaborative activity that offered OCV to one region of the Artibonite Department of rural Haiti in addition to other ongoing treatment and control measures. Despite logistics and cold chain challenges, 45,417 persons were successfully vaccinated with OCV in the region, and 90.8% of these persons completed their second dose