Functionalization of Gold and Silicon Surfaces by Copolymer Brushes Using Surface‐Initiated ATRP

Surface‐initiated ATRP was used for step‐by‐step growth of poly(butyl methacrylate)‐co‐poly(2,2‐dimethylaminoethyl methacrylate) (PBMA‐co‐PDMAEMA) brushes from gold and silicon substrates. A one‐step procedure was found to have high efficiency for initiator anchoring. The polymer brushes were characterized in situ by contact angle measurements, ellipsometry, and X‐ray photoelectron spectroscopy (XPS). Detachment of the polymer brushes from both substrates allowed an exact determination of molecular weight and polydispersity indexes given by GPC. ¹H NMR confirmed the chemical structure of the detached brushes. Comparison of theoretical predictions and experimental data showed that the first PBMA block had a folded conformation while copolymerization of the second DMAEMA induced stretching of the brushes.

     

Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo

Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention. The NO chimera, GT-094, is a novel nitrate containing an NSAID and disulfide pharmacophores, a lead compound for the design of agents specifically for colorectal cancer. GT-094 is the first nitrate reported to reduce aberrant crypt foci (by 45%) when administered after carcinogen in the standard azoxymethane rat model of colorectal cancer. Analysis of proximal and distal colon tissue from 8- and 28-week rat/azoxymethane studies showed that GT-094 treatment reduced colon crypt proliferation by 30% to 69%, reduced inducible NO synthase (iNOS) levels by 33% to 67%, reduced poly(ADP-ribose)polymerase-1 expression and cleavage 2- to 4-fold, and elevated levels of p27 in the distal colon 3-fold. Studies in cancer cell cultures recapitulated actions of GT-094: antiproliferative activity and transient G(2)-M phase cell cycle block were measured in Caco-2 cells; apoptotic activity was examined but not observed; anti-inflammatory activity was seen in the inhibition of up-regulation of iNOS and endogenous NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In summary, antiproliferative, anti-inflammatory, and cytoprotective activity observed in vivo and in vitro support GT-094 as a lead compound for the design of NO chimeras for colorectal cancer chemoprevention.     

Quantitative [<Superscript>18</Superscript>F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer

Purpose

Evaluation of [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer.

Procedures

Mice with BT474, HER2+ tumors, were imaged with [¹⁸F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging.

Results

[¹⁸F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P?<?0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P?<?0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r ² ?=?0.85).

Conclusions

[¹⁸F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.

     

A Qualitative Study of a Maintenance Support Program for Women at Risk of Homelessness: Part 1: Personal Factors

In this article, a qualitative study of homeless women and their experiences attending a Maintenance Support Programme (MSP) is discussed. The overarching theme that emerged from the study of women in the MSP was ‘A life-changing event: I have the power to change’. The article focuses on the first of the sub-themes: personal factors including: (a) health status, (b) beliefs and attitudes, (c) knowledge, and (d) life and interpersonal skills. Findings demonstrate the influence that these factors have on the capacity of homeless women to change their lives. The MSP was instrumental in supporting these women to manage personal issues, by assisting with accessing health and social services, and developing life skills and achieving life goals. Understanding the homeless women's experiences may inform the development of future programmes and services in order to support and empower them to break the cycle of homelessness and help them to lead meaningful lives within society.     

Experiences and Perceived Social Support among Iranian Men on Methadone Maintenance Therapy: A Qualitative Study

The use of drugs predominantly among Iranian men leads to health and social problems. Iran has established methadone maintenance therapy centres but there is limited research exploring the experiences of men who make use of this therapy. The aim of this qualitative study was to explore the experiences of men on methadone maintenance therapy in Urmia, Iran. Sixteen opioid-dependent males on methadone syrup substitution therapy were interviewed. Transcribed data were subjected to thematic analysis. Three themes emerged from the data: (1) the role of family in drug addiction; (2) the role of environment in drug addiction; and (3) the support needed to overcome drug addiction. While drug rehabilitation programmes in Iran can help the person, their family is seen as the most important support that they need together with sociocultural acceptance to overcome stigmatisation.     

Back to the beginning: Perceptions of older Singaporean couples living alone

Singapore has an aging population that is projected to increase by 32% in 2100. The majority of older couples live alone. “Aging in Place” is an initiative that is widely promoted by the government, in which older people are supported to live in their own homes. In this qualitative study, we explored the perceptions of older people living with their spouse in Singapore. Fifteen community‐dwelling older participants were interviewed. Four themes emerged from the thematic analysis: (i) maintaining health and mobility; (2) maintaining relationships with spouse; (iii) maintaining relationship with others; and (iv) living the last leg of the race. The older people living on their own were generally content about maintaining their interdependence and complementary roles. Insights gathered from this study have relevance to implementation of the Aging‐in‐Place policy to ensure that older people receive the support they need to maintain their physical and psychosocial well‐being while living on their own.     

ERBB activation modulates sensitivity to MEK1/2 inhibition in a subset of driver-negative melanoma

Melanomas are characterized by activating “driver” mutations in BRAF, NRAS, KIT, GNAQ, and GNA11. Resultant mitogen-activated protein kinase (MAPK) pathway signaling makes some melanomas susceptible to BRAF (BRAF V600 mutations), MEK1/2 (BRAF V600, L597, fusions; NRAS mutations), or other kinase inhibitors (KIT), respectively. Among driver-negative (“pan-negative”) patients, an unexplained heterogeneity of response to MEK1/2 inhibitors has been observed. Analysis of 16 pan-negative melanoma cell lines revealed that 8 (50%; termed Class I) are sensitive to the MEK1/2 inhibitor, trametinib, similar to BRAF V600E melanomas. A second set (termed Class II) display reduced trametinib sensitivity, paradoxical activation of MEK1/2 and basal activation of ERBBs 1, 2, and 3 (4 lines, 25%). In 3 of these lines, PI3K/AKT and MAPK pathway signaling is abrogated using the ERBB inhibitor, afatinib, and proliferation is even further reduced upon the addition of trametinib. A potential mechanism of ERBB activation in Class II melanomas is minimal expression of the ERK1/2 phosphatase, DUSP4, as ectopic restoration of DUSP4 attenuated ERBB signaling through potential modulation of the ERBB ligand, amphiregulin (AREG). Consistent with these data, immunohistochemical analysis of patient melanomas revealed a trend towards lower overall DUSP4 expression in pan-negative versus BRAF- and NRAS-mutant tumors. This study is the first to demonstrate that differential ERBB activity in pan-negative melanoma may modulate sensitivity to clinically-available MEK1/2 inhibitors and provides rationale for the use of ERBB inhibitors, potentially in combination with MEK1/2 inhibitors, in subsets of this disease.     

Transcultural adaptation of the Night Eating Questionnaire (NEQ) for its use in the Spanish population

BackgroundEstablishing valid and reliable methods of assessing night eating symptoms is an important goal to maximize identification and treatment of the night eating syndrome (NES). The 14-item Night Eating Questionnaire (NEQ) is the only published and validated assessment instrument but is not yet adapted to Spanish.MethodsWe examined the factor structure, internal consistency and validity of the NEQ in Spanish. The study had 4 phases: a) translation from English to Spanish; b) back-translation from Spanish to English, c) administration of translated version to a Spanish sample, and d) a re-test in 36 participants two weeks later. Reliability, stability, and scale structure were evaluated by Cronbach's α, test–re-test, and factor analysis, respectively. Divergent validity was assessed by correlation with the Spanish versions of the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI-II).ResultsTwo-hundred forty-four individuals (181 f; BMI 34.3 ± 10 kg/m²; age 40.5 ± 15 y) completed the questionnaire. The mean NEQ score was 12.5 ± 7. The Cronbach's α coefficient for the total score was 0.79, the intraclass correlation was 0.85, and the factor analysis yielded a similar four factor solution as the original scale. Correlation for the test–re-test total score was 0.86. Total NEQ score was significantly correlated with the BDI-II (r = 0.48 p < 0.001), but this correlation was not significant during the test–re-test (r = 0.28, p = 0.10) or with STAI at either time point (0.05, p = 0.40; r = 0.07, p = 0.69, respectively).ConclusionsThe Spanish version of the NEQ demonstrated adequate internal consistency for the majority of domains and excellent reproducibility. There was divergent validity with anxiety and a relationship between night eating and depression. These results suggest that the Spanish-version of the NEQ is an instrument that is valid for use in clinical research.     

Managing cancer‐related fatigue in men with prostate cancer: A systematic review of non‐pharmacological interventions

The aim of this systematic review was to synthesize the best available evidence informing the effectiveness of non‐pharmacological interventions for managing cancer‐related fatigue in men treated for prostate cancer. This review considered experimental studies that included men with prostate cancer (regardless of staging, previous treatment or comorbidities), aged 18 years and over who were undergoing any treatment, or had completed any treatment for prostate cancer within the previous 12 months. Three interventions were identified for the management of cancer‐related fatigue in men with prostate cancer. Evidence from five studies including 447 participants demonstrates the effectiveness of physical activity, both aerobic and resistance exercise, and from three studies including 153 participants suggesting the benefits of psychosocial interventions including education and cognitive behavioural therapy. Health professionals require knowledge of a range of effective interventions aimed at reducing cancer‐related fatigue in men with prostate cancer and should incorporate those interventions into their patient management. Although physical activity appears to show the greatest benefit, other non‐pharmacological interventions such as education and cognitive behavioural therapy have demonstrated benefit and should also be considered as a strategy in treating this debilitating side effect of cancer and its treatment.