Symptoms and symptom distress in localized prostate cancer

For over a decade, symptom distress has been a key concept in several studies of cancer. However, the definition of symptom distress is still unclear, and there are few measures targeting symptom distress, in general, and specific cancers, in particular. Prostate cancer is the sixth most common cancer worldwide and the second leading cause of death in American men. Many men with clinically localized prostate cancer may experience unique and multidimensional symptoms that occur from diagnosis through treatment, and thereafter. These symptoms associated with the disease and its treatments are in the form of physical and psychological sequelae such as urinary and bowel problems and sexual dysfunction. The purposes of this article are to (1) systematically review literature on symptoms and symptom distress in localized prostate cancer and (2) synthesize evidence of symptom distress applications and measurement in this group. A comprehensive, systematic review was conducted to identify original, data-based studies of symptoms and symptom distress in localized prostate cancer. Clarification of symptom distress and more comprehensive information about symptoms and symptom distress will provide nurses with a better foundation for developing self-management interventions aimed at ameliorating symptom distress and, ultimately, enhancing the quality of life of patients with localized prostate cancer.     

Key challenges in providing services to people who use drugs: The perspectives of people working in emergency departments and shelters in Atlantic Canada

Aims: Many people who use drugs (PWUD) have multiple health and social needs, and research suggests that this population is increasingly accessing emergency departments (EDs) and shelters for health care and housing. This qualitative study explored the practices of those working in EDs and shelters when providing services to PWUD, with a particular focus on key challenges in service provision. Methods: EDs and shelters were conceptualized as ‘micro environments’ with various components (i.e. social, physical and resource). One-on-one interviews were conducted with 57 individuals working in EDs and shelters in Atlantic Canada. Findings: The social, physical and resource environments within some EDs and shelters are key forces in shaping the challenges facing those providing services. For example, the social environments within these settings are focused on acute health care in the case of EDs, and housing in the case of shelters. These mandates do not encompass the complex needs of many PWUD. Resource issues within the wider community (e.g. limited drug treatment spaces) further contribute to the challenges. Conclusions: Structural issues, internal and external to EDs and shelters need to be addressed to reduce the challenges facing many who work in these settings when providing services to PWUD.     

Molecular and Phylogenetic Characterization of Novel Papillomaviruses Isolated from Oral and Anogenital Neoplasms of Japanese Macaques (Macaca fuscata)

Papillomaviruses (PVs) are a diverse group of host species-specific DNA viruses, etiologically linked with various benign and malignant neoplasms of cutaneous and mucosal epithelia. Here, we describe the detection and characterization of the first two PVs naturally infecting Japanese macaques (Macaca fuscata), including the determination of their etiological association(s) with the development of original neoplasms. The molecular and phylogenetic analyses were performed on complete genome sequences of Macaca fuscata PV types 1 (MfuPV1) and 2 (MfuPV2), which were completely sequenced in samples of a malignant oral tumor and benign anogenital neoplasm of Japanese macaques, respectively. Subsequently, two type-specific quantitative real-time PCRs were developed to estimate viral loads of MfuPV1 and MfuPV2 and to evaluate their etiological roles. The in silico molecular analyses revealed that both viral genomes encode characteristic PV proteins with conserved functional domains and have a non-coding genomic region with regulatory sequences to regulate and complete the viral life cycle. However, additional experimental evidence is needed to finally confirm the presence and biological functionality of the molecular features of both novel PVs. While MfuPV1, together with PVs identified in other macaques, is classified into the Alphapapillomavirus (Alpha-PV) species 12, MfuPV2 is most likely a representative of the novel viral species within the Alpha-PV genus. Their relatively high viral loads suggest that both PVs are etiologically linked with the development of the original neoplasms.     

Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist

Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with activators of the TRAIL pathway that activate the alternative (death receptor) apoptotic pathway. Herein, we demonstrate that the HDACi vorinostat synergizes with the mouse DR5-specific monoclonal antibody MD5-1 to induce rapid and robust tumor cell apoptosis in vitro and in vivo. Importantly, using a preclinical mouse breast cancer model, we show that the combination of vorinostat and MD5-1 is safe and induces regression of established tumors, whereas single agent treatment had little or no effect. Functional analyses revealed that rather than mediating enhanced tumor cell apoptosis via the simultaneous activation of the intrinsic and extrinsic apoptotic pathways, vorinostat augmented MD5-1-induced apoptosis concomitant with down-regulation of the intracellular apoptosis inhibitor cellular-FLIP (c-FLIP). These data demonstrate that combination therapies involving HDACi and activators of the TRAIL pathway can be efficacious for the treatment of cancer in experimental mouse models.     

Step training improves the speed of voluntary step initiation in aging

BACKGROUND: Falls related to balance dysfunction are among the major problems of older individuals. The timing characteristics of protective voluntary stepping are critically related to effective balance recovery and are often delayed and slowed with age. This study investigated the influence of step training on the timing characteristics of voluntary step initiation in younger and older adults. METHODS: Voluntary reaction time stepping was evaluated before and after training in 12 younger adults and 8 healthy community-dwelling older adults who performed a 3-week regimen of either twice weekly induced step training (destabilizing large waist pulls) or voluntary step practice to a somatosensory reaction stimulus cue (nondestabilizing small waist pulls). RESULTS: Overall, the first step initiation times were slower for the older than for the younger subjects for both the somatosensory reaction stimulus cue task and an auditory transfer cue task. Step completion time was completed earlier for the young posttraining subjects, and older subjects generally had a longer step length. Training resulted in significant reductions in step initiation timing for the old (17%) and young (15%) subjects. Across age groups, the induced training group showed greater reductions in step initiation time than the voluntary practice group for the auditory transfer cue task. CONCLUSIONS: A 3-week period of either voluntary or waist-pull-induced step training reduced step initiation time in older and younger adults. Moreover, compared with voluntary step practice, induced step training resulted in a significantly greater improvement in reaction time stepping for an auditory transfer cue task. At least in the short term, such step training has the potential to help older adults perform more like younger adults in their step initiation timing.