Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials.

In an effort to develop cancer therapies that maximize cytotoxicity, while minimizing unwanted side effects, we studied a series of novel compounds based on the highly energetic heterocyclic scaffold, dinitroazetidine. In this study, we report the preclinical validation of 1-bromoacetyl-3,3-dinitroazetidine (ABDNAZ), a representative lead compound currently in a phase I clinical trial in patients with cancer. In tumor cell culture, ABDNAZ generated reactive free radicals in a concentration- and time-dependent manner, modulating intracellular redox status and triggering apoptosis.

Darinaparsin: solid tumor hypoxic cytotoxin and radiosensitizer.

Purpose: Hypoxia is an important characteristic of the solid tumor microenvironment and constitutes a barrier for effective radiotherapy. Here, we studied the effects of darinaparsin (an arsenic cytotoxin) on survival and radiosensitivity of tumor cells in vitro under normoxia and hypoxia and in vivo using xenograft models, compared to effects on normal tissues.

Experimental Design: The cytotoxicity and radiosensitization of darinaparsin were first tested in vitro in a variety of solid tumor cell lines under both normoxia and hypoxia and compared with arsenic trioxide (ATO, an arsenical with reported cytotoxic and radiosensitizing activities on tumor cells).

Is Nitric Oxide (NO) the Last Word in Radiosensitization? A Review.

As a short-lived radical that diffuses across membranes, rather than interacting with membrane-bound receptors, nitric oxide (NO) represents a significant departure from synthetically derived radiosensitizers. An endogenous compound, NO may equal or surpass its molecular cousin, oxygen, as a hypoxic radiosensitizer, through pleiotropic phenotypic effects on tumor perfusion, cell signaling, mitochondrial respiration, the fixation of radiation-induced damage, and the radioprotection of normal tissue. However, unlike oxygen, in the context of radiosensitization, the clinical role and utility of NO are poorly understood, with often contradictory and controversial reported effects: whether NO functions as a radiosensitizer may ultimately be contextual to the tumor microenvironment.

Mitigation of radiation-induced dermatitis by activation of aldehyde dehydrogenase 2 using topical alda-1 in mice.

Radiation-induced dermatitis is a debilitating clinical problem in cancer patients undergoing cancer radiation therapy. It is also a possible outcome of exposure to high levels of radiation due to accident or hostile activity. We report that activation of aldehyde dehydrogenase 2 (ALDH2) enzymatic activity using the allosteric agonist, Alda-1, significantly reduced 4-hydroxynonenal adducts accumulation, delayed the onset of radiation dermatitis and substantially reduced symptoms in a clinically-relevant model of radiation-induced dermatitis.

Association between depressive symptoms and metabolic syndrome in police officers: results from two cross-sectional studies.

Policing is one of the most dangerous and stressful occupations and such stress can have deleterious effects on health. The purpose of this study was to examine the association between depressive symptoms and metabolic syndrome (MetSyn) in male and female police officers from two study populations, Buffalo, NY and Spokane, WA. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale.

Salivary gland organogenesis.

Our understanding of vertebrate salivary gland organogenesis has been largely informed by the study of the developing mouse submandibular gland (SMG), which will be the major focus of this review. The mouse SMG has been historically used as a model system to study epithelial-mesenchymal interactions, growth factor-extracellular matrix (ECM) interactions, and branching morphogenesis. SMG organogenesis involves interactions between a variety of cell types and their stem/progenitor cells, including the epithelial, neuronal, and mesenchymal cells, and their ECM microenvironment, or niche.

The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C.

Unlabelled: Tegobuvir (GS-9190), a non-nucleoside nonstructural protein (NS)5B polymerase inhibitor, and GS-9256, an NS3 serine protease inhibitor, individually have activity against hepatitis C virus (HCV) genotype 1. The antiviral activity of tegobuvir and GS-9256 as oral combination therapy, or together with ribavirin (RBV) or pegylated interferon (Peg-IFN) alpha-2a and RBV, was assessed in a phase II, randomized, open-label trial. Treatment-naïve patients with genotype 1 HCV were assigned 28 days of tegobuvir 40 mg twice-daily (BID) and GS-9256 75 mg BID (n = 16), tegobuvir and GS-9256 plus RBV 1,000-1,200 mg daily (n = 15), or tegobuvir and GS-9256 plus Peg-IFN alpha-2a (180 μg once-weekly)/RBV (n = 15).

Time trade-off derived EQ-5D weights for Australia.

Background: Cost-utility analyses (CUAs) are increasingly common in Australia. The EuroQol five-dimensional (EQ-5D) questionnaire is one of the most widely used generic preference-based instruments for measuring health-related quality of life for the estimation of quality-adjusted life years within a CUA. There is evidence that valuations of health states vary across countries, but Australian weights have not previously been developed.

Preferences for new and existing contraceptive products.

New contraceptive methods provide greater choice in terms of effectiveness, management of side-effects, convenience and frequency of administration and flexibility, but make the decisions about contraception more complex. There are limited data on the factors that determine women's choices among these alternatives, to inform providers about the factors which are most important to women, or to predict uptake of new products. This paper reports on a choice experiment designed to elicit women's preferences in relation to prescribed contraception and to forecast the impact of the introduction of two new products into the Australian market.

Six degrees of separation: the oxygen effect in the development of radiosensitizers.

The popular theory six degrees of separation is used in this review as an analogy to relate all radiosensitization to oxygen. As the prime mover of all radiosensitizers, the pervasive influence of oxygen has consciously or unconsciously influenced the direction of research and development and provided the benchmark against which all other compounds and approaches are measured. It is the aim of this review to develop the six degrees of separation from oxygen analogy as a unifying framework for conceptually organizing the field and for giving context to its varied subspecializations and theories.

Perfluorocarbon exposure, gender and thyroid function in the C8 Health Project.

Perfluorocarbons from common household products such as food containers, stain- resistant protection for clothing, furniture and carpets, paints, and fire-fighting foams are found in soil, water, plants, animal and human serum worldwide. Previous research has shown a significant association between these chemicals and thyroid disease in women. The present data from the C8 Health Project assessed thyroid function in a cross-sectional analysis of 52,296 adults with a year or more of exposure to perfluorooctanoate (PFOA) from drinking water.

Diet, environmental factors, and lifestyle underlie the high prevalence of vitamin D deficiency in healthy adults in Scotland, and supplementation reduces the proportion that are severely deficient.

Vitamin D deficiency has recently been implicated as a possible risk factor in the etiology of numerous diseases, including nonskeletal conditions. In humans, skin synthesis following exposure to UVB is a potent source of vitamin D, but in regions with low UVB, individuals are at risk of vitamin D deficiency. Our objectives were to describe the prevalence of vitamin D deficiency and to investigate determinants of plasma 25-hydroxyvitamin D (25-OHD) concentrations in a high northern latitude country.

Supervisor self-disclosure: supervisees' experiences and perspectives.

Twelve graduate-level supervisees were interviewed regarding their experiences of supervisor self-disclosure (SRSD); data were analyzed using consensual qualitative research. When describing a specific SRSD experience, supervisees reported a range of antecedents (e.g.

Metabolic syndrome and carotid intima media thickness in urban police officers.

Objective: To examine the association between metabolic syndrome (MetSyn) and carotid intima media thickness (IMT) separately in male and female police officers.

Methods: MetSyn was defined using 2005 guidelines. B-mode ultrasound was used to measure mean and maximum (12 and 36 segments) carotid artery thickness.

Use of patient group directions in an emergency care centre.

Patient group directions (PGDs) enable practitioners who are not independent prescribers to administer or supply patients with medications. They reduce delays in the administration of medication and thereby improve patients' journeys. This article discusses an audit of the use of PGDs in an emergency care centre to ensure that they are used appropriately and regularly.

The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty.

Background: Studies indicate that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with a range of disease processes, many of which are inflammatory. However, other lipid-soluble vitamins decrease during the systemic inflammatory response, and this response may confound the interpretation of plasma 25(OH)D.

Objective: The objective was to examine whether plasma 25(OH)D concentrations change during evolution of the systemic inflammatory response.

Implications of early menopause in women exposed to perfluorocarbons.

Context: Perfluorocarbons (PFC) are man-made chemicals used in numerous household products. They have a long half-life in humans and complex animal toxicity, and accumulating evidence points toward associations with multiple human health endpoints.

Objective: Our objective was to investigate whether PFC are associated with endocrine disruption in women.

Clients' perspectives on therapy termination.

We used consensual qualitative research to analyze interviews with 12 clients about their termination from psychotherapy. Those who had positive termination experiences reported a strong therapeutic relationship and positive outcomes of therapy. They terminated primarily for logistical or financial reasons; their termination, post-termination plans, and feelings about termination were discussed in advance with their therapist, as was their growth in therapy, leading to mostly positive effects of the termination.

Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration.

An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors, after therapeutic radiation of head and neck tumors, as a result of Sjögren's syndrome and in genetic syndromes affecting gland development. The permanent loss of gland function impairs the oral health of these patients and broadly affects their quality of life. The regeneration of functional salivary gland tissue is thus an important therapeutic goal for the field of regenerative medicine and will likely involve stem/progenitor cell biology and/or tissue engineering approaches.

Associations between police officer stress and the metabolic syndrome.

The purpose of this study was to examine the association of police officer stress with metabolic syndrome (MetSyn) and its individual components. Participants included 288 men and 102 women from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Study. Police stress was measured using the Spielberger police stress survey.

AGT M235T genotype/anxiety interaction and gender in the HyperGEN study.

Background: Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups.

Methodology: The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style).

Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis.

The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells.

The use of dreams in modern psychotherapy.

We review theories of dream work. We also review the empirical research about how dreams are used in psychotherapy, as well as the process and outcome of different models of dream work. Finally, we review how dream content can be used to understand client, the role of culture in dream work, client and therapist dreams about each other, and training therapists to do dream work.

Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats.

We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation therapy and intetumumab in human cancer xenograft models in nude rats to assess effects on both tumor cells and the tumor microenvironment. Nude rats bearing human head and neck cancer and non-small cell lung cancer (NSCLC) xenografts were treated with intetumumab and fractionated local tumor radiotherapy.