Every Day Counts: a randomized pilot lifestyle intervention for women with metastatic breast cancer.

PURPOSE: To explore the feasibility, adherence, safety and potential efficacy of Every Day Counts; a randomized pilot trial designed for women with metastatic breast cancer (MBC) framed by the American Cancer Society nutrition and physical activity (PA) guidelines METHODS: Women with clinically stable MBC were recruited to complete an interview, dual energy X-ray absorptiometry imaging and phlebotomy at baseline and post-intervention. Multidimensional quality of life, symptom burden, lifestyle behaviors (nutrition and PA) and biomarkers of prognosis were procured and quantified. Women were randomized to the immediate intervention or a waitlist control arm. The 12-week intervention included a curriculum binder, lifestyle coaching (in-person and telephone-based sessions) and intervention support (activity monitor, text messaging, cooking classes.) Women in the waitlist control were provided monthly text messaging. RESULTS: Forty women were recruited within 9 months (feasibility). Women in the immediate intervention attended 86% of all 12 weekly coaching sessions (adherence) and showed significant improvements in general QOL (p = 0.001), and QOL related to breast cancer (p = 0.001), endocrine symptoms (p = 0.002) and fatigue (p = 0.037), whereas the waitlist control did not (all p values ≥ 0.05) (efficacy). PA significantly increased for women in the intervention compared to control (p < 0.0001), while dietary changes were less evident across groups due to high baseline adherence. No significant changes in biomarkers or lean mass were noted, yet visceral adipose tissue declined (p = 0.001). No intervention-related injuries were reported (safety). Qualitative feedback strongly supports the desire for a longer intervention with additional support. CONCLUSIONS: Lifestyle interventions are of interest, safe and potentially beneficial for women with MBC. A larger trial is warranted.

Injectable nanofibrillar hydrogels based on charge-complementary peptide co-assemblies.

Injectable hydrogels are attractive for therapeutic delivery because they can be locally administered through minimally-invasive routes. Charge-complementary peptide nanofibers provide hydrogels that are suitable for encapsulation of biotherapeutics, such as cells and proteins, because they assemble under physiological temperature, pH, and ionic strength. However, relationships between the sequences of charge-complementary peptides and the physical properties of the hydrogels that they form are not well understood. Here we show that hydrogel viscoelasticity, pore size, and pore structure depend on the pairing of charge-complementary "CATCH(+/-)" peptides. Oscillatory rheology demonstrated that co-assemblies of CATCH(4+/4-), CATCH(4+/6-), CATCH(6+/4-), and CATCH(6+/6-) formed viscoelastic gels that can recover after high-shear and high-strain disruption, although the extent of recovery depends on the peptide pairing. Cryogenic scanning electron microscopy demonstrated that hydrogel pore size and pore wall also depend on peptide pairing, and that these properties change to different extents after injection. In contrast, no obvious correlation was observed between nanofiber charge state, measured with ζ-potential, and hydrogel physical properties. CATCH(4+/6-) hydrogels injected into the subcutaneous space elicited weak, transient inflammation whereas CATCH(6+/4-) hydrogels induced stronger inflammation. No antibodies were raised against the CATCH(4+) or CATCH(6-) peptides following multiple challenges in vehicle or when co-administered with an adjuvant. These results demonstrate that CATCH(+/-) peptides form biocompatible injectable hydrogels with viscoelastic properties that can be tuned by varying peptide sequence, establishing their potential as carriers for localized delivery of therapeutic cargoes.

Silver treatments and silver-impregnated dressings for the healing of leg wounds and ulcers: a systematic review and meta-analysis.

Previous systematic reviews of silver-impregnated dressings have been contradictory regarding the healing of leg wounds/ulcers. Our systematic review was restricted to randomized controlled trials. Cochrane Library, Scopus, and MEDLINE databases were searched using the term "silver" in combination with "wound" or "ulcer" (and plural versions) without date/language restriction. Study quality was assessed and meta-analysis conducted for complete wound healing, wound size reduction, and healing rates. Overall study quality was fair with most studies having some bias. Evidence for wound healing using individual studies was poor. Meta-analyses found strong evidence for wound healing based on wound size reduction but no evidence based on complete wound-healing or healing rates. Although our results provide some evidence that silver-impregnated dressings improve the short-term healing of wounds and ulcers, long-term effects remain unclear. Clinical trial data with longer follow-up times are needed to address these issues.

Cataract surgery rates in latin america: a four-year longitudinal study of 19 countries.

PURPOSE: To collect cataract surgery rates data in 19 Latin American countries over a 4-year period as data published to date have been limited. METHODS: Cataract surgery rates were obtained from National Society of Ophthalmology, National VISION 2020/Prevention of Blindness Committee and Ministry of Health representatives for each country for 2005 to 2008. Economic (gross national income per capita) and other data were collected from publicly available databases. Linear and power correlations between gross national incomes and cataract surgery rates were calculated. RESULTS: Over the study period, most countries increased their cataract surgery rates, with the largest increases observed for Venezuela (186%), Nicaragua (183%), Costa Rica (100%), Uruguay (97%), and Peru (88%). Mean cataract surgery rates for 2005, 2006, 2007, and 2008 for the ensemble of countries were 1545, 1684, 1660, and 1822 per million population, respectively, with a growth over the study period of 17.9%, concurrent with an increase of 57 million (11.5%) in the population. A good correlation between cataract surgery rate and gross national income per capita was found (P < .001). CONCLUSIONS: Although progress is being made in the region, the cataract surgery rates represent only one parameter. When they are examined in the context of cataract surgical coverage it is clear that substantial proportions of bilaterally blind persons are still not receiving surgery.

Interplay between HIV-1 Vpr and Sp1 modulates p21(WAF1) gene expression in human astrocytes.

The Vpr (viral protein R) of human immunodeficiency virus, type 1, which is expressed during the late stage of the viral infection, has received special attention because of its ability to control transcription of the human immunodeficiency virus, type 1, long terminal repeat and to influence cell cycle progression. Here we demonstrate that Vpr has the ability to regulate transcription of the cyclin-dependent kinase inhibitor, p21(WAF1) (p21), one of the key regulators of the cell cycle, in human astrocytic cells. The results from transcription assays demonstrated that Vpr augments promoter activity of p21 through the GC-rich region located between nucleotides -84 and -74 with respect to the +1 transcription start site. Activation of p21 by Vpr required cooperativity of Sp1, which binds to the DNA sequence spanning -84 to -74. Results from bandshift assay revealed an increased level of Sp1 DNA binding activity in the presence of Vpr. Furthermore, Vpr was able to associate with Sp1 via the zinc finger domain located in the C-terminal region of Sp1. Functional studies revealed that the cooperativity between Vpr and Sp1 requires the zinc finger domain at the C terminus and the glutamine-rich domain at the N terminus of Sp1. Expression of p53 further enhanced the level of Vpr-Sp1-mediated transcription activation of p21 through the sequence spanning -84 to -74 and increased the DNA binding activity of Sp1 in the presence of Vpr. Results from glutathione S-transferase pull-down assay showed the association of Vpr with p53 in extracts containing Sp1. Altogether, the outcome of our functional and binding studies suggested that the physical interaction of Vpr with Sp1 and p53 could modulate transcriptional activity of p21.