Early Palliative Care Reduces End-of-Life Intensive Care Unit (ICU) Use but Not ICU Course in Patients with Advanced Cancer

Background.

Early palliative care for advanced cancer patients improves quality of life and survival, but less is known about its effect on intensive care unit (ICU) use at the end of life. This analysis assessed the effect of a comprehensive early palliative care program on ICU use and other outcomes among patients with advanced cancer.

Patients and Methods.

A retrospective cohort of patients with advanced cancer enrolled in an early palliative care program (n = 275) was compared with a concurrent control group of patients receiving standard care (n = 195) during the same time period by using multivariable logistic regression analysis. The multidisciplinary outpatient palliative care program used early end-of-life care planning, weekly interdisciplinary meetings to discuss patient status, and patient-reported outcomes assessment integrated within the electronic health record.

Results.

Patients in the control group had statistically significantly higher likelihood of ICU admission at the end of life (odds ratios [ORs]: last 6 months, 3.07; last month, 3.59; terminal admission, 4.69), higher likelihood of death in the hospital (OR, 4.14) or ICU (OR, 5.57), and lower likelihood of hospice enrollment (OR, 0.13). Use of chemotherapy or radiation did not significantly differ between groups, nor did length of ICU stay, code status, ICU procedures (other than cardiopulmonary resuscitation), disposition location, and outcomes after ICU admission.

Conclusion.

Early palliative care significantly reduced ICU use at the end of life but did not change ICU events. This study supports early initiation of palliative care for advanced cancer patients before hospitalizations and intensive care. The Oncologist 2017;22:1–6

Implications for Practice: Palliative care has shown clear benefit in quality of life and survival in advanced cancer patients, but less is known about its effect on intensive care. This retrospective cohort study at a university hospital showed that in the last 6 months of life, palliative care significantly reduced intensive care unit (ICU) and hospital admissions, reduced deaths in the hospital, and increased hospice enrollment. It did not, however, change patients' experiences within the ICU, such as number of procedures, code status, length of stay, or disposition. The findings further support that palliative care exerts its benefit before, rather than during, the ICU setting.

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Population-Level Differences in Rectal Cancer Survival in Uninsured Patients Are Partially Explained by Differences in Treatment

Background.

Rectal cancer (RC) is a common malignancy with a substantial mortality but good survival for patients with optimally treated nonmetastatic disease. Lack of insurance may compromise access to care and therefore compromise survival. Here, we examine RC survival by insurance type.

Methods.

Data from the Surveillance, Epidemiology, and End Results database were used to determine 1- to 3-year survival for patients with RC by insurance type (Medicaid, uninsured, other insurance).

Results.

Patients with Medicaid or no insurance presented at later stages and were less likely to receive definitive surgery. Overall 3-year survival was higher for patients with other insurance compared with Medicaid-insured (+22.2% units) and uninsured (+18.8% units) patients. Major differences in survival were still observed after adjustment for stage. When patients with stage II and III RC were considered, 3-year survival was higher for patients with other insurance versus those with Medicaid (+16.2% units) and uninsured patients (+12.2% units). However, when the analysis was limited to patients with stage II and III disease who received radiation therapy followed by definitive surgery, the difference decreased to +11.8% units and +7.3% units, respectively, for Medicaid and no insurance.

Conclusion.

For patients with stage II and III RC, much of the difference in survival between uninsured patients and those with insurance other than Medicaid can be explained by differences in treatment. Further efforts to determine the cause of residual differences as well as efforts to improve access to standard-of-care treatment for uninsured patients may improve population-level survival for RC. The Oncologist 2017;22:1–8

Implications for Practice: Insurance status affects survival for patients with rectal cancer, but a substantial proportion of the difference in survival can be corrected if standard-of-care treatment is given. Every effort should be made to ensure that uninsured or publically insured patients receive standard-of-care treatment with as little delay as possible to improve patient outcomes.

Implications for Practice: Insurance status affects survival for patients with rectal cancer, but a substantial proportion of the difference in survival can be corrected if standard-of-care treatment is given. Every effort should be made to ensure that uninsured or publically insured patients receive standard-of-care treatment with as little delay as possible to improve patient outcomes.

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Molecular Subtypes Improve Prognostic Value of International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Model

Introduction.

Gene-expression signatures for prognosis have been reported in localized renal cell carcinoma (RCC). The aim of this study was to test the predictive power of two different signatures, ClearCode34, a 34-gene signature model [Eur Urol 2014;66:77–84], and an 8-gene signature model [Eur Urol 2015;67:17–20], in the setting of systemic therapy for metastatic disease.

Materials and Methods

Metastatic RCC (mRCC) patients from five institutions who were part of TCGA were identified and clinical data were retrieved. We trained and implemented each gene model as described by the original study. The latter was demonstrated by faithful regeneration of a figure and results from the original study. mRCC patients were dichotomized to good or poor prognostic risk groups using each gene model. Cox proportional hazard regression and concordance index (C-Index) analysis were used to investigate an association between each prognostic risk model and overall survival (OS) from first-line therapy.

Results.

Overall, 54 patients were included in the final analysis. The primary endpoint was OS. Applying the ClearCode34 model, median survival for the low-risk—ccA (n = 17)—and the high-risk—ccB (n = 37)—subtypes were 27.6 and 22.3 months (hazard ratio (HR): 2.33; p = .039), respectively. ClearCode34 ccA/ccB and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) classifications appear to represent distinct risk criteria in mRCC, and we observed no significant overlap in classification (p > .05, chi-square test). On multivariable analyses and adjusting for IMDC groups, ccB remained independently associated with a worse OS (p = .044); the joint model of ccA/ccB and IMDC was significantly more accurate in predicting OS than a model with IMDC alone (p = .045, F-test). This was also observed in C-Index analysis; a model with both ccA and ccB subtypes had higher accuracy (C-Index 0.63, 95% confidence interval [CI] = 0.51–0.75) and 95% CIs of the C-Index that did not include the null value of 0.5 in contrast to a model with IMDC alone (0.60, CI = 0.47–0.72). The 8-gene signature molecular subtype model was a weak but insignificant predictor of survival in this cohort (p = .13). A model that included both the 8-gene signature and IMDC (C-Index 0.62, CI = 0.49–0.76) was more prognostic than IMDC alone but did not reach significance, as the 95% CI included the null value of 0.5. These two genomic signatures share no genes in common and are enriched in different biological pathways. The ClearCode34 included genes ARNT and EPAS1 (also known as HIF2a), which are involved in regulation of gene expression by hypoxia-inducible factor.

Conclusion.

The ClearCode34 but not the 8-gene molecular model improved the prognostic predictive power of the IMDC model in this cohort of 54 patients with metastatic clear cell RCC. The Oncologist 2017;22:1–7

Implications for Practice: The clinical and laboratory factors included in the International Metastatic Renal Cell Carcinoma Database Consortium model provide prognostic information in metastatic renal cell carcinoma (mRCC). The present study shows that genomic signatures, originally validated in localized RCC, may add further complementary prognostic information in the metastatic setting. This study may provide new insights into the molecular basis of certain mRCC subgroups. The integration of clinical and molecular data has the potential to redefine mRCC classification, enhance the understanding of mRCC biology, and potentially predict response to treatment in the future.

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Using Metaphors to Explain Molecular Testing to Cancer Patients

Background.

Molecular testing to identify targetable molecular alterations is routine practice for several types of cancer. Explaining the underlying molecular concepts can be difficult, and metaphors historically have been used in medicine to provide a common language between physicians and patients. Although previous studies have highlighted the use and effectiveness of metaphors to help explain germline genetic concepts to the general public, this study is the first to describe the use of metaphors to explain molecular testing to cancer patients in the clinical setting.

Methods.

Oncologist-patient conversations about molecular testing were recorded, transcribed verbatim, and coded. If a metaphor was used, patients were asked to explain it and assess its helpfulness.

Results.

Sixty-six patients participated. Nine oncologists used metaphors to describe molecular testing; 25 of 66 (38%) participants heard a metaphor, 13 of 25 (52%) were questioned, 11 of 13 (85%) demonstrated understanding and reported the metaphor as being useful. Seventeen metaphors (bus driver, boss, switch, battery, circuit, broken light switch, gas pedal, key turning off an engine, key opening a lock, food for growth, satellite and antenna, interstate, alternate circuit, traffic jam, blueprint, room names, Florida citrus) were used to explain eight molecular testing terms (driver mutations, targeted therapy, hormones, receptors, resistance, exon specificity, genes, and cancer signatures).

Conclusion.

Because metaphors have proven to be a useful communication tool in other settings, these 17 metaphors may be useful for oncologists to adapt to their own setting to explain molecular testing terms. The Oncologist 2017;22:1–5

Implications for Practice: This article provides a snapshot of 17 metaphors that proved useful in describing 8 complicated molecular testing terms at 3 sites. As complex tumor sequencing becomes standard of care in clinics and widely used in clinical research, the use of metaphors may prove a useful communication tool, as it has in other settings. Although this study had a small sample, almost all of the patients who were exposed to metaphors in explaining molecular testing reported it as being helpful to their understanding. These 17 metaphors are examples of potentially useful communication tools that oncologists can adapt to their own practice.

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The Antiproliferative Role of Lanreotide in Controlling Growth of Neuroendocrine Tumors: A Systematic Review

Background.

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors, with >50% of cases involving the gastrointestinal system or pancreas. Somatostatin analogs (SSAs) are used for treating NET-related secretory syndromes and, more recently, for their antiproliferative effects. We conducted a systematic review of published literature on the antiproliferative efficacy and safety of the SSA lanreotide Autogel in the management of NETs to gain a fuller understanding of the evidence and identify future areas of research.

Methods.

Searches were conducted in PubMed up to March 16, 2016, and in the proceedings of four congresses from 2013 to 2016.

Results.

Screening of 1,132 publications identified in the searches found 40 relevant publications, including 27 full-length publications and 13 congress abstracts. Twenty-four of these publications reported antiproliferative efficacy data for lanreotide Autogel. The CLARINET study showed that 120 mg lanreotide Autogel every 4 weeks improves progression-free survival (PFS) in patients with gastroenteropancreatic (GEP)-NETs, with grade 1 or grade 2 (Ki-67 <10%) disease, providing class I evidence of its antiproliferative effects. The CLARINET open-label extension study reported a median PFS of 32.8 months with lanreotide Autogel. Other smaller studies generally support CLARINET.

Conclusion.

Current clinical evidence shows that lanreotide Autogel has good antiproliferative activity with favorable safety and tolerability in patients with GEP-NETs, suggesting it should be considered as an early first-line treatment in this population. Further studies are needed to assess the potential benefits of higher doses and the use of lanreotide Autogel in combination therapy and as maintenance therapy in the absence of disease progression following other therapies. The Oncologist 2017;22:1–14

Implications for Practice: This review presents the current clinical evidence for the antiproliferative activity of lanreotide Autogel in patients with midgut or pancreatic neuroendocrine tumors (NETs) and shows its effectiveness, safety, and tolerability in these patient populations. By systematically presenting all the clinical evidence, the review adds to existing publications by discussing results in a broad range of settings. The review also indicates future directions for investigation of the use of lanreotide Autogel in NETs originating in other locations, in combination therapy, or as maintenance therapy in progressive disease.

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Randomized Phase II Study of Ramucirumab or Icrucumab in Combination with Capecitabine in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer

Background.

Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced or metastatic breast cancer.

Methods.

Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m² orally twice daily, days 1–14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM + CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR + CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics.

Results.

Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1–36.1) weeks on RAM + CAP, 7.3 (6.3–13.0) weeks on ICR + CAP, and 19.0 (12.1–24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p = .1315, RAM + CAP versus CAP; 1.480, p = .0851, ICR + CAP versus CAP). Median OS was 67.4 weeks on RAM + CAP, 62.1 weeks on ICR + CAP, and 71.6 weeks on CAP (HRs: 1.833, p = .0283, RAM + CAP versus CAP; 1.468, p = .1550, ICR + CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥10%) on RAM + CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥10%) on ICR + CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea.

Conclusion.

Combining RAM or ICR with CAP did not improve PFS in the targeted study population. The Oncologist 2017;22:1–10

Implications for Practice

Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and -2), respectively. VEGFR-1 activation on endothelial and tumor cell surfaces increases tumor vascularization and growth and supports tumor growth via multiple mechanisms, including contributions to angiogenesis and direct promotion of cancer cell proliferation. Strong preclinical and clinical evidence suggests key roles for VEGF and angiogenesis in breast cancer growth, invasion, and metastasis. This randomized phase II study evaluated the efficacy and safety of each antibody in combination with capecitabine in patients with previously treated unresectable, locally advanced or metastatic breast cancer.

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Survival of patients with colorectal peritoneal metastases is affected by treatment disparities among hospitals of diagnosis: A nationwide population-based study

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Koen P. Rovers, Geert A. Simkens, Pauline A. Vissers, Valery E. Lemmens, Victor J. Verwaal, Andre J. Bremers, Marinus J. Wiezer, Jacobus W. Burger, Patrick H. Hemmer, Henk Boot, Wilhelmina M. van Grevenstein, Wilhelmus J. Meijerink, Arend G. Aalbers, Cornelis J. Punt, Pieter J. Tanis, Ignace H. de Hingh
BackgroundIn the Netherlands, surgery for peritoneal metastases of colorectal cancer (PMCRC) is centralised, whereas PMCRC is diagnosed in all hospitals. This study assessed whether hospital of diagnosis affects treatment selection and overall survival (OS).MethodsBetween 2005 and 2015, all patients with synchronous PMCRC without systemic metastases were selected from the Netherlands Cancer Registry. Treatment was classified as cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), systemic therapy or other/no treatment. Hospitals of diagnosis were classified as: (1) non-teaching or academic/teaching hospital and (2) HIPEC centre or referring hospital. Referring hospitals were further classified based on the frequency of CRS/HIPEC as high-, medium- or low-frequency hospital. Multivariable regression analyses were used to assess the independent influence of hospital categories on the likelihood of CRS/HIPEC and OS.ResultsA total of 2661 patients, diagnosed in 89 hospitals, were included. At individual hospital level, CRS/HIPEC and systemic therapy ranged from 0% to 50% and 6% to 67%, respectively. Hospital of diagnosis influenced the likelihood of CRS/HIPEC: 33% versus 13% for HIPEC centres versus referring hospitals (odds ratio (OR) 3.66 [2.40−5.58]) and 11% versus 17% for non-teaching hospitals versus academic/teaching hospitals (OR 0.60 [0.47–0.77]). Hospital of diagnosis affected median OS: 14.1 versus 9.6 months for HIPEC centres versus referring hospitals (hazard ratio (HR) 0.82 [0.67–0.99]) and 8.7 versus 11.5 months for non-teaching hospitals versus academic/teaching hospitals (HR 1.15 [1.06–1.26]). Compared with diagnosis in medium-frequency referring hospitals, median OS was increased in high-frequency referring hospitals (12.6 months, HR 0.82 [0.73−0.91]) and reduced in low-frequency referring hospitals (8.1 months, HR 1.12 [1.01–1.24]).ConclusionTreatment disparities among hospitals of diagnosis and their impact on survival indicate suboptimal treatment selection for PMCRC.



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Phase-II trials in osteosarcoma recurrences: A systematic review of past experience

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Natacha Omer, Marie-Cécile Le Deley, Sophie Piperno-Neumann, Perrine Marec-Berard, Antoine Italiano, Nadège Corradini, Carine Bellera, Laurence Brugières, Nathalie Gaspar
BackgroundThe most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined.ObjectiveTo study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results.MethodsSystematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II).ResultsAmong the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%.ConclusionNo robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point.



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Anthropometrics at birth and risk of a primary central nervous system tumour: A systematic review and meta-analysis

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Marios K. Georgakis, Eleni I. Kalogirou, Athanasios Liaskas, Maria A. Karalexi, Paraskevi Papathoma, Kyriaki Ladopoulou, Maria Kantzanou, Georgios Tsivgoulis, Eleni Th. Petridou
BackgroundThe aetiology of primary central nervous system (CNS) tumours remains largely unknown, but their childhood peak points to perinatal parameters as tentative risk factors. In this meta-analysis, we opted to quantitatively synthesise published evidence on the association between birth anthropometrics and risk of primary CNS tumour.MethodsEligible studies were identified via systematic literature review; random-effects meta-analyses were conducted for the effect of birth weight and size-for-gestational-age on childhood and adult primary CNS tumours; subgroup, sensitivity, meta-regression and dose–response by birth weight category analyses were also performed.ResultsForty-one articles, encompassing 53,167 CNS tumour cases, were eligible. Birth weight >4000 g was associated with increased risk of childhood CNS tumour (OR: 1.14, [1.08–1.20]; 22,330 cases). The risk was higher for astrocytoma (OR: 1.22, [1.13–1.31]; 7456 cases) and embryonal tumour (OR: 1.16, [1.04–1.29]; 3574 cases) and non-significant for ependymoma (OR: 1.12, [0.94–1.34]; 1374 cases). Increased odds for a CNS tumour were also noted among large-for-gestational-age children (OR: 1.12, [1.03–1.22]; 10,339 cases), whereas insufficient data for synthesis were identified for other birth anthropometrics. The findings remained robust across subgroup and sensitivity analyses controlling for several sources of bias, whereas no significant heterogeneity or publication bias were documented. The limited available evidence on adults (4 studies) did not reveal significant associations between increasing birth weight (500-g increment) and overall risk CNS tumour (OR: 0.99, [0.98–1.00]; 1091 cases) or glioma (OR: 1.03, [0.98–1.07]; 2052 cases).ConclusionsThis meta-analysis confirms a sizeable association of high birth weight, with childhood CNS tumour risk, particularly astrocytoma and embryonal tumour, which seems to be independent of gestational age. Further research is needed to explore underlying mechanisms, especially modifiable determinants of infant macrosomia, such as gestational diabetes.



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Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Donella Puliti, Lauro Bucchi, Silvia Mancini, Eugenio Paci, Susanna Baracco, Cinzia Campari, Debora Canuti, Claudia Cirilli, Natalina Collina, Giovanni Maria Conti, Enza Di Felice, Fabio Falcini, Maria Michiara, Rossella Negri, Alessandra Ravaioli, Priscilla Sassoli de' Bianchi, Monica Serafini, Manuel Zorzi, Adele Caldarella, Luigi Cataliotti, Marco Zappa
BackgroundThe objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence.MethodsThe cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias.ResultsOverall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06–1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01–1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57–0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76–0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68–0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates.ConclusionsComparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+.



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Rationale for stimulator of interferon genes–targeted cancer immunotherapy

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines. In 2008, STING (stimulator of interferon genes), was identified as a protein that is indispensable for the recognition of cytosolic DNA. The central role of STING in controlling anticancer immune responses was exemplified by observations that spontaneous and radiation-induced adaptive anticancer immunity was reduced in the absence of STING, illustrating the potential of STING-targeting for cancer immunotherapy. Here, we will discuss the relevance of manipulating the STING signalling pathway for cancer treatment and integrating STING-targeting based strategies into combinatorial therapies to obtain long-lasting anticancer immune responses.



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Can chance cause cancer? A causal consideration

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Mats Julius Stensrud, Susanne Strohmaier, Morten Valberg, Odd Olai Aalen
The role of randomness, environment and genetics in cancer development is debated. We approach the discussion by using the potential outcomes framework for causal inference. By briefly considering the underlying assumptions, we suggest that the antagonising views arise due to estimation of substantially different causal effects. These effects may be hard to interpret, and the results cannot be immediately compared. Indeed, it is not clear whether it is possible to define a causal effect of chance at all.



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Comparative analysis of PD-L1 expression between primary and metastatic pulmonary adenocarcinomas

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Sehui Kim, Jaemoon Koh, Dohee Kwon, Bhumsuk Keam, Heounjeong Go, Young A Kim, Yoon Kyung Jeon, Doo Hyun Chung
Programmed death-ligand 1 (PD-L1) expression in pulmonary adenocarcinomas (pADCs) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, the differential expression of PD-L1 between primary and metastatic pADC remains unclear. Thus, we addressed this issue. In total, 161 paired primary and metastatic tumour tissues from 146 patients with pADC were collected. Most of the cases had regional nodal metastasis (134/161, 83.2%). PD-L1 expression was categorised based on the proportion of immunostained tumour cells using cutoff values of 1%, 5%, 10% and 50%. In primary tumours, PD-L1 positivity was observed in 28.1% (41/146), 27.4% (40/146), 22.6% (33/146) and 13.0% (19/146) of cases using cutoff values of 1%, 5%, 10% and 50%, respectively. The overall concordance rate for PD-L1 expression between primary and metastatic tumours was 75.2% (121/161). The concordance rate in primary tumours expressing PD-L1 in <1% or ≥50% of tumour cells was 87.2% (102/117) or 70% (14/20), respectively. In contrast, the concordance rate in tumours expressing PD-L1 in ≥1% to <50% of cells was only 20.8% (5/24). After dichotomising the cases using cutoff values of 1% and 50%, the concordance rate increased to 80.1% (129/161) and 90.7% (146/161) in all paired cases and to 70.4% (19/27) and 85.2% (23/27) in cases with distant metastases, respectively. This study demonstrates that the concordance of PD-L1 expression between primary and metastatic pADC is high when using cutoff values of 1% and 50%. Thus, evaluation of PD-L1 in either primary or metastatic tumours would be helpful for guiding anti–PD-1/PD-L1 immunotherapy in patients with advanced pADC.



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In situ-synthesized cadmium sulfide nanowire photosensor with a parylene passivation layer for chemiluminescent immunoassays

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Ju-Hee Im, Hong-Rae Kim, Byoung-Gi An, Young Wook Chang, Min-Jung Kang, Tae-Geol Lee, Jin Gyeng Son, Jae-Gwan Park, Jae-Chul Pyun
The direct in situ synthesis of cadmium sulfide (CdS) nanowires (NWs) was presented by direct synthesis of CdS NWs on the gold surface of an interdigitated electrode (IDE). In this work, we investigated the effect of a strong oxidant on the surfaces of the CdS NWs using X-ray photoelectron spectroscopy, transmission electron microscopy, and time-of-flight secondary ion mass spectrometry. We also fabricated a parylene-C film as a surface passivation layer for in situ-synthesized CdS NW photosensors and investigated the influence of the parylene-C passivation layer on the photoresponse during the coating of parylene-C under vacuum using a quartz crystal microbalance and a photoanalyzer. Finally, we used the in situ-synthesized CdS NW photosensor with the parylene-C passivation layer to detect the chemiluminescence of horseradish peroxidase and luminol and applied it to medical detection of carcinoembryonic antigen.



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A magnetite/PMAA nanospheres-targeting SERS aptasensor for tetracycline sensing using mercapto molecules embedded core/shell nanoparticles for signal amplification

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Huanhuan Li, Quansheng Chen, Md. Mehedi Hassan, Xiaoxing Chen, Qin Ouyang, Zhiming Guo, Jiewen Zhao
Surface-enhanced Raman scattering (SERS) biosensors have promising potential in the field of antibiotics detection because of their ultrahigh detection sensitivity. This paper reports a rapid and sensitive SERS-based magnetic nanospheres-targeting strategy for sensing tetracycline (TTC) using aptamer-conjugated magnetite colloid nanocrystal clusters (MCNCs)-polymethacrylic acid (PMAA) magnetic nanospheres (MNs) as the recognition and the Au/PATP/SiO2 (APS) as the labels. Initially, MNs were fabricated and conjugated with the aptamers through condensation reaction. MNs possessed high saturation magnetization (Ms) value of 71.5emu/g and excellent biocompatibility, which facilitated the rapid and easy magnetic separation. Then, complementary DNA (cDNA) were loaded on the APS nanocarrier to produce a large amplification factor of Raman signals. The MNs-targeting aptasensor was thus fabricated by immobilizing the APS to the MNs' surfaces via the hybrid reaction between cDNA and aptamers. Sequel, TTC bound successfully to the aptamer upon its addition with the subsequent release of some cDNA-APS into the bulk solution. Under magnet attraction, the nanospheres were deposited together. Consequently, a display of strong SERS signals by supernatants of the resulting mixtures with increasing TTC concentrations was observed. The proposed aptasensor showed excellent performances for TTC detection along with wide linear range of 0.001–100ng/mL, low detection limit 0.001ng/mL, high sensitivity, and good selectivity to the general coexisted interferences.



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Direct and label-free influenza virus detection based on multisite binding to sialic acid receptors

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yukichi Horiguchi, Tatsuro Goda, Akira Matsumoto, Hiroaki Takeuchi, Shoji Yamaoka, Yuji Miyahara
A system to discriminate human or avian influenza A remains a highly sought-after tool for prevention of influenza pandemics in humans. Selective binding of the influenza A viral hemagglutinin (HA) to specific sialic acid (SA) receptors (Neu5Acα(2-6)Gal in humans, Neu5Acα(2-3)Gal in birds) is determined by the genotype of the HA and neuraminidase (NA) segments, making it one of the key characteristics that distinguishes human or avian influenza A virus. Here we demonstrate the direct detection of whole H1N1 influenza A virus using 6′-sialyllactose (Neu5Acα(2-6)Galβ(1-4)Glc, 6SL)-immobilized gold electrodes as biosensing surfaces. The sensitivity was higher than that of conventional immunochromatographic technique (ICT) for influenza virus and not restricted by genetic drift. The label-free detection technology via direct attachment of a whole virus using a chemically modified electrode is a promising means to provide a simple and rapid diagnostic system for viral infections.



http://ift.tt/2lFD2B8

Tuning of the selectivity of fluorescent peptidyl bioprobe using aggregation induced emission for heavy metal ions by buffering agents in 100% aqueous solutions

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Lok Nath Neupane, Gi Won Hwang, Keun-Hyeung Lee
Smart fluorescent probes of which the detection of specific target molecules can be controlled are attracting remarkable interest. A fluorescent peptidyl bioprobe (1) was rationally synthesized by conjugating tetraphenylethylene, an aggregation-induced emission (AIE) fluorophore with a peptide receptor (AspHis) that acted as hard and intermediate bases. The selective detection of 1 for specific metal ion in 100% aqueous solutions was controlled by the buffering agents with the chelate effect without the change of pH. In distilled water and phosphate buffered aqueous solution at neutral pH, 1 exhibited a selective Off-On response to a soft metal ion, Hg²⁺ among test metal ions by 100-fold enhancement of the emission at 470nm. 1 showed a selective Off-On response (180-fold enhancement) to a hard metal ion, Al³⁺ ions among test metal ions in Tris buffered aqueous solution at neutral pH and Hexamine (hexamethylenetetramine) buffered aqueous solution at acidic pH. The detection limit of 0.46 ppb for Hg²⁺ and 2.26 ppb for Al³⁺ in each condition was lower than the maximum allowable level of the metal ions in drinking water by EPA. This research helps to understand how buffering agents participate in the complex formation and aggregation of fluorescent probes using an AIE process for the selective detection of specific metal ions in aqueous solutions.



http://ift.tt/2kT3v9O

Versatile transduction scheme based on electrolyte-gated organic field-effect transistor used as immunoassay readout system

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Benoît Piro, Dengjun Wang, Dihia Benaoudia, Alexandra Tibaldi, Guillaume Anquetin, Vincent Noël, Steeve Reisberg, Giorgio Mattana, Brianna Jackson
We report on an innovative heterogeneous bisphenol A (BPA) immunoassay based on an electrolyte-gated organic field-effect transistor whose organic semiconductor is poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene) co-crystallized with an alkyl derivative of bisphenol A. A decrease of the transistor output current is first observed upon antibody specific binding onto the organic semiconductor. Upon bisphenol A addition, the competitive dissociation of the antibody from the semiconductor surface leads to an opposite increase of the output current. We present here a proof-of-concept for bisphenol A detection; the device could be readily adapted to other small organic molecules of interest and is a promising tool for simple, low-cost, portable and easy-to-use biosensors.

Graphical abstract

http://ift.tt/2lFNWa7

A novel turn-on fluorescent strategy for sensing ascorbic acid using graphene quantum dots as fluorescent probe

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Hua Liu, Weidan Na, Ziping Liu, Xueqian Chen, Xingguang Su
In this paper, a facile and rapid fluorescence turn-on assay for fluorescent detection of ascorbic acid (AA) was developed by using the orange emission graphene quantum dots (GQDs). In the presence of horse radish peroxidase (HRP) and hydrogen peroxide (H2O2), catechol can be oxidized by hydroxyl radicals and converted to o-benzoquinone, which can significantly quench the fluorescence of GQDs. However, when AA present in the system, it can consume part of H2O2 and hydroxyl radicals to inhibit the generation of o-benzoquinone, resulting in fluorescence recovery. Under the optimized experimental conditions, the fluorescence intensity was linearly correlated with the concentration of H2O2 in the range of 3.33–500µM with a detection limit of 1.2µM. The linear detection for AA was in the range from 1.11 to 300µM with a detection limit of 0.32µM. The proposed method was applied to the determination of AA in human serum samples with satisfactory results.



http://ift.tt/2lFD2kC

TiO2 nanowire arrays modified with a simultaneous “etching, doping and deposition” technique for ultrasensitive amperometric immunosensing

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Xiaoqiang Liu, Xiaohe Huo, Peipei Liu, Yunfei Tang, Jun Xu, Huangxian Ju
In this work, an ultrasensitive immunosensing scaffold was structured with TiO2 nanowire (TiNW) arrays modified with molybdenum (Mo) and MoS2 flakes by a triplex "etching, doping and deposition" technique. The triply modification of TiNW arrays improved their electron transfer, and the decoration of MoS2 flakes on TiNW arrays increased both the conductivity and the specific surface area of TiNW. Accordingly, the triply modified TiNW arrays provided a biocompatible microenviroment for the biomolecules and high specific surface area to load big amount of biomolecules. The immunosensor was prepared by immobilizing capture antibody on the scaffold surface with double amino-reactive crosslinker, and the tracing labels were prepared by immobilizing signal antibody and horseradish peroxidase molecules on cylinder-shaped TiO2 nanorods. After sandwich-type immunoreaction, the tracing labels were quantitatively captured on the immunosensor surface for the detection of carcinoembryonic antigen as a model analyte. This amperometric method showed a linear range of 0.001 and 150ngmL⁻¹ with a detection limit of 0.5pgmL⁻¹. This work provided a promising platform for sensitive amperometric immunosensing of protein biomarkers.



http://ift.tt/2kSTcCP

Schneller Nachweis sepsiserregender Pilze

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 85-85
DOI: 10.1055/s-0043-100282

Georg Thieme Verlag KG Stuttgart · New York

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Heparininduzierte Thrombozytopenie: Argatoban überzeugt

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 80-80
DOI: 10.1055/s-0042-121867

Tardy-Poncet B et al. Argatroban in the management of heparin induced thrombocytopenia: a multicenter clinical trial. Critical Care 2015; 19: 396 Zur Therapie der heparininduzierten Thrombozytopenie (HIT) ist ein alternatives Antikoagulans notwendig, um das damit einhergehende Thromboserisiko zu senken und die geplante Antikoagulation grundsätzlich weiterzuführen. Zur Verfügung steht u. a. der vorwiegend hepatisch metabolisierte Thrombininhibitor Argatoban. Tardy-Poncet et al. prüften, ob sich dieser Wirkstoff zur parenteralen Therapie einer HIT bei Patienten eignet, für die andere Nicht-Heparine zur Antikoagulation kontraindiziert sind.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Anästhetika und Sedativa: FDA-Warnung für Kinder und Schwangere

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 87-87
DOI: 10.1055/s-0043-100452

Georg Thieme Verlag KG Stuttgart · New York

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Supraklavikuläre oder interskalenäre Plexusblockaden?

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 80-84
DOI: 10.1055/s-0043-100154

Wiesmann T et al. Phrenic palsy and analgesic quality of continuous supraclavicular vs. interscalene plexus blocks after shoulder surgery. Acta Anaesthesiol Scand 2016; 60: 1142–1151 Zur postoperativen Schmerztherapie bei arthroskopischen Schultereingriffen werden häufig interskalenäre Plexuskatheter angelegt. Wegen der Nähe des Katheters zum N. phrenicus kommt es dabei häufig durch das verabreichte Lokalanästhetikum zu Phrenikusparesen mit einseitigem Zwerchfellhochstand.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Immer mehr traumatisierte Flüchtlinge in Spezialzentren

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 86-86
DOI: 10.1055/s-0043-100288

Georg Thieme Verlag KG Stuttgart · New York

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Sättigungsabfall postoperativ häufiger als erwartet

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 82-83
DOI: 10.1055/s-0042-121866

Sun Z et al. Postoperative hypoxemia is common and persistent: a prospective blinded observational study. Anesth Analg 2015; 121: 709–715 Ein Abfall der pulsoxymetrisch gemessenen O2-Sättigung nach OPs tritt häufig auf und ist oftmals prolongiert. Zu dieser Erkenntnis kam ein Forscherteam um Zhuo Sun in Ohio (USA) und Ontario (Canada).
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Alle Analgetika in einem Buch

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 88-88
DOI: 10.1055/s-0042-107481

Georg Thieme Verlag KG Stuttgart · New York

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Opioidmedikation: keine erhöhte Sturzneigung und Frakturgefahr

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 83-84
DOI: 10.1055/s-0043-100155

Krebs EE et al. Association of opioids with falls, fractures, and physical performance among older men with persistent musculoskeletal pain. J Gen Intern Med 2016; 31: 463–469 Stürze und Frakturen sind bei älteren Personen häufige Gründe für eine Vorstellung in der Notaufnahme. Alte Personen sind häufiger von muskuloskelettalen Schmerzen betroffen. Ob die daraus resultierende häufigere Dauermedikation mit Opioiden zu vermehrten Stürzen und Frakturen führt, wird in der folgenden Studie untersucht.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Notaufnahme statt Hausarzt

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 86-86
DOI: 10.1055/s-0043-100277

Georg Thieme Verlag KG Stuttgart · New York

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Intravenös verabreichtes Fentanyl durch (Rettungs-)Sanitäter

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 84-84
DOI: 10.1055/s-0043-100151

Friesgaard KD et al. Efficacy and safety of intravenous fentanyl administered by ambulance personnel. Acta Anaesthesiol Scand 2016; 60: 537–543 Intravenös verabreichtes Fentanyl reduziert effektiv Schmerzen bei den meisten Patienten und kann sicher durch geschultes Sanitätspersonal eingesetzt werden. Dies zeigte eine Studie der Ärzte des Rettungsdiensts der Region Arhus in Dänemark um Friesgaard.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Neuer Wirkstoff lindert neuropathischen Schmerz

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 86-87
DOI: 10.1055/s-0043-100300

Georg Thieme Verlag KG Stuttgart · New York

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Neuer Aufklärungsbogen zu Anästhesie und Überwachungsmaßnahmen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 85-86
DOI: 10.1055/s-0043-100275

Georg Thieme Verlag KG Stuttgart · New York

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1000 Fragen – und noch viel mehr Antworten

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 88-89
DOI: 10.1055/s-0042-107479

Georg Thieme Verlag KG Stuttgart · New York

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Um die Hintergründe zu verstehen

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 88-88
DOI: 10.1055/s-0042-107487

Georg Thieme Verlag KG Stuttgart · New York

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Ultrahochvolumen-Hämofiltration wenig überzeugend

Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 80-81
DOI: 10.1055/s-0042-121860

Quenot JP et al. Very high volume hemofiltration with the cascade system in septic shock patients. Intensive Care Med 2015: 2111–2120 Im septischen Schock soll die Hoch-Volumen-Hämofiltration (HVHF) der Überschwemmung mit inflammatorischen Zytokinen entgegenwirken und ein Multiorganversagen verhindern. Dabei geht auch Gutes verloren: Proteine, Elektrolyte, Antibiotika, andere niedrigmolekulare Substanzen und viel Flüssigkeit müssen kontrolliert substituiert werden. Jean-Pierre Quenot et al. überprüften nun die Sicherheit und Effektivität des Cascade-Systems, das mit 2 Filtern und Reinfusion arbeitet.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Structure and luminescence properties of Ce3+ doped KBa1−x(Mg/Zn)xY(BO3)2 and K1−yNayBaY(BO3)2 phosphors evolved from cation substitution

Publication date: 1 August 2017
Source:Optics & Laser Technology, Volume 93
Author(s): Rui Xu, Yujun Liang, Shiqi Liu, Yingli Zhu, Xingya Wu, Kai Li, Wei Zhou
The tunable blue-emitting KBa1−x(Mg/Zn)xY0.95(BO3)2:0.05Ce³⁺ and K1−yNayBaY0.95(BO3)2:0.05Ce³⁺ phosphors have been investigated via cation substitution of Mg²⁺/Zn²⁺ for Ba²⁺ and Na⁺ for K⁺ in KBaY(BO3)2 host. The crystal structures, photoluminescence properties, thermal stability and the effect of Mg²⁺/Zn²⁺/Na⁺ concentration on the luminescence characteristics were investigated in detail. The XRD analysis implied that KBa1−x(Mg/Zn)xY(BO3)2 solid solutions were limited, while continuous solid solution was possible in K1−yNayBaY(BO3)2 system. Upon the excitation at 365nm, the emission peaks of KBa1−x(Mg/Zn)xY0.95(BO3)2:0.05Ce³⁺ (0⩽x⩽0.6) blue-shifted from 435 to 424nm, and K1−yNayBaY0.95(BO3)2:0.05Ce³⁺ (0⩽y⩽1) blue-shifted from 435 to 427nm with the Mg²⁺/Zn²⁺/Na⁺ doping concentration increase. The thermal stabilities of KBa1−x(Mg/Zn)xY0.95(BO3)2:0.05Ce³⁺ phosphors were enhanced from 20°C to 200°C by increasing the concentration of Mg²⁺ and Zn²⁺. The substitution of Na⁺ for K⁺ led to a decrease in the proportion of ⁵D-²F5/2 and ⁵D-²F7/2 corresponding to the Gaussian fitting of Ce³⁺ in K1−yNayBaY0.95(BO3)2:0.05Ce³⁺ phosphors. At the temperature increased, the full width at half maximum of photoluminescence band of K0.8Na0.2BaY0.95(BO3)2:0.05Ce³⁺ decreased. However, the decreasing trend of FWHM became less obvious with the increasing concentration of Na⁺ in the temperature dependent photoluminescence spectra of K1−yNayBaY0.95(BO3)2:0.05Ce³⁺ phosphors.



http://ift.tt/2lggeXM

Ultrasonic assisted synthesis of a tetrazine functionalized MOF and its application in colorimetric detection of phenylhydrazine

Publication date: July 2017
Source:Ultrasonics Sonochemistry, Volume 37
Author(s): Sayed Ali Akbar Razavi, Mohammad Yaser Masoomi, Ali Morsali
TMU-34(-2H), [Zn(OBA)(DPT)0.5].DMF, has been sonochemically synthesized by applying H2OBA, (4,4′-oxybis(benzoic acid)), as the dicarboxylate linker, and DPT, (3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine), as pillar spacer. Sonication time, concentration of initial reagents, sonication power and molar ratio of pyridine as modulator has been optimized to synthesize nano powder of TMU-34(-2H) including uniform plate morphology. Nano TMU-34(-2H), can detect phenylhydrazine (PH) by color changing from pink to deep purple. As a comparison, nano and crystal samples of TMU-34(-2H) were treated to detect PH. Experiments show that nano TMU-34(-2H) has better detection limit and response time.



http://ift.tt/2kSX3ji

Mechanism, kinetics and thermodynamics of carbon dioxide hydrogenation to methanol on Cu/ZnAl2O4 spinel-type heterogeneous catalysts

Publication date: 15 June 2017
Source:Applied Catalysis B: Environmental, Volume 207
Author(s): Matej Huš, Venkata D.B.C. Dasireddy, Neja Strah Štefančič, Blaž Likozar
Heterogeneous catalytic hydrogenation of gaseous carbon dioxide to methanol is an important reduction reaction in chemical process engineering, renewable energy industry and emerging green chemistry, as it provides means to harness surplus electrical energy and convert a pollutant and emitted greenhouse gas into a useful building block and biofuel. On industrial operating scale, multifunctional copper/zinc catalysts on various supporting substrates (e.g. CZA with alumina) are most commonly used due to their high selectivity and conversion. In this work, post-Hartree–Fock and density functional theory (DFT) calculations were carried out to assess the thermodynamics and to elucidate the pathway leading to the formation of methanol from CO2 on realistic spinel-type tri-metallic materials. Firstly, a commercial-like Cu/ZnO/Al2O3 was synthesised via co-precipitation and characterised to obtain the active sites' structure for modelling. Powder X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) surface area measurement, scanning/transmission electron microscopy (SEM and TEM) and energy-dispersive X-ray spectroscopy (EDS) were performed. Subsequently, the Gibbs free energy, enthalpy, entropy and chemical equilibrium constants of the direct methanol synthesis and the competing reverse water–gas shift (RWGS) reaction at the temperatures of 25, 150, 200, 250 and 300°C, and the pressures of 1, 20, 40, 60 and 100bar were evaluated using ab initio quantum chemistry method CCSD(T)/aug-cc-pVQZ. To investigate kinetics, a mechanistic pathway scheme with all established intermediates was constructed, whereas physical/chemical adsorption/desorption energies, geometries, barriers and rates for adsorbate elementary steps were calculated using plane-wave DFT. Results demonstrate that the formate precursor route predominates as the respective transition state activation energies are lower and, thus CH3OH is proposed to form through HCOO, H2COO, H2COOH, CH2O and CH3O species.

Graphical abstract

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Enhanced ferromagnetism in ZnGdO nanoparticles induced by Al co-doping

Publication date: 25 May 2017
Source:Journal of Alloys and Compounds, Volume 705
Author(s): B. Poornaprakash, U. Chalapathi, B. Purusottam Reddy, P.T. Poojitha, Si-Hyun Park
Dilute magnetic semiconductors with extended ferromagnetic properties are heavily sought for use in next-generation spintronic devices. In this work, we show that co-doping 3 at% Al into Zn0.44Gd0.03O0.50 nanoparticles can change their magnetic nature from weak to well-defined ferromagnetism (FM) at room temperature. X-ray diffraction (XRD), selected area electron diffraction (SAED), and Raman spectroscopy show that the Gd and Al atoms replaced the Zn atoms in the ZnO crystal lattice without forming other impurity phases. Field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) analyses of the suspensions revealed the high crystallinity and monodispersity of the 34–44 nm nanoparticles. The undoped and Gd-doped ZnO samples showed diamagnetism and weak FM, while the (Gd, Al) co-doped samples exhibited robust room temperature FM. The enhanced FM of the Zn0.44Gd0.03Al0.03O0.50 sample can be achieved by increasing the carrier concentration via Al co-doping.



http://ift.tt/2lgkaYE

The effect of structural and optical properties on the photocatalytic efficiency of Zinc Sulphide nanoparticles obtained by hydro/solvothermal decomposition of Zinc N,N-diethyldithiocarbamate

Publication date: June 2017
Source:Journal of Physics and Chemistry of Solids, Volume 105
Author(s): G.O. Siqueira, E.C.R. de Morais, H.V. da Silva, A. Abelenda, J.C. González, A.O. Porto
Cubic and hexagonal zinc sulphide nanoparticles were prepared by hydro/solvothermal decomposition of Zinc N,N-diethyldithiocarbamate by using different experimental conditions such as pH values, solvents and the presence of a particle stabilizer, sodium polyacrylate. The effect of these different experimental conditions on the microstructure and photocatalytical efficiency of ZnS was investigated in this work. Microstructural parameters, such as, apparent mean crystal size, microstrain and crystal size distribution were determined by analysis of experimental X-ray diffraction. Apparent mean crystal sizes were in the range of 6.5–44nm and the lattice microstrain varied from 0.24% to 0%. Dimethylformamide showed to be more suitable than water to form small particles with a very narrow size distribution. The obtained optical band gaps and Urbach energies were in range of 3.32–3.60eV and 0.09–0.15eV, respectively. Photoluminescence spectra showed strong visible light emissions (green, blue and white) associated to the electronic levels introduced by the presence of superficial defects. The photocatalytic efficiency of these samples was investigated towards methylene blue degradation and a correlation between this efficiency and the PL intensity was observed. This correlation was associated to the formation of surface active centres at catalyst surfaces and the local potential fluctuations of valence and conduction bands.



http://ift.tt/2kT1ZEB

Structural, theoretical and corrosion inhibition studies on some transition metal complexes derived from heterocyclic system

Publication date: 5 June 2017
Source:Journal of Molecular Structure, Volume 1137
Author(s): Shraddha Rani Gupta, Punita Mourya, M.M. Singh, Vinod P. Singh
A Schiff base, (E)-N′-((1H-indol-3-yl)methylene)-2-aminobenzohydrazide (Iabh) and its Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized. These compounds have been characterized by different physico-chemical and spectroscopic tools (UV–Vis, IR, NMR and ESI-Mass). The molecular structure of Iabh is determined by single crystal X-ray diffraction technique. The ligand Iabh displays E-configuration about the >CN− bond. The structure of ligand is stabilized by intra-molecular H-bonding. In all the metal complexes the ligand coordinates through azomethine-N and carbonyl-O resulting a distorted octahedral geometry for Mn(II), Co(II) and Cu(II) complexes in which chloride ions occupy axial positions. Ni(II) and Zn(II) complexes, however, form 4-coordinate distorted square planer and tetrahedral geometry around metal ion, respectively. The structures of the complexes have been satisfactorily modeled by calculations based on density functional theory (DFT) and time dependent-DFT (TD-DFT). The corrosion inhibition study of the compounds have been performed against mild steel in 0.5 M H2SO4 solution at 298 K by using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). They show appreciable corrosion inhibition property.

Graphical abstract

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Effect of ZnSe/GaAs interface treatment in ZnSe quality control for optoelectronic device applications

Publication date: 31 May 2017
Source:Applied Surface Science, Volume 405
Author(s): Kwangwook Park, Daniel Beaton, Kenneth X. Steirer, Kirstin Alberi
We investigate the role of interface initiation conditions on the growth of ZnSe/GaAs heterovalent heterostructures. ZnSe epilayers were grown on a GaAs surface with various degrees of As-termination and the application of either a Zn or Se pre-treatment. Structural analysis revealed that Zn pre-treatment of an As-rich GaAs surface suppresses Ga2Se3 formation at the interface and promotes the growth of high crystal quality ZnSe. This is confirmed with low-temperature photoluminescence. However, moderation of Ga-Se bonding through a Se pre-treatment of an As-rich GaAs surface can prevent excessive intermixing at the interface and promote excitonic emission in the underlying GaAs layer. These results provide guidance on how best to prepare heterovalent interfaces for various applications.



http://ift.tt/2lgtawz

Microstructure and mechanical properties of Mg-Nd-Zn-Zr alloy processed by integrated extrusion and equal channel angular pressing

Publication date: 25 May 2017
Source:Journal of Alloys and Compounds, Volume 705
Author(s): Sicong Zhao, Erjun Guo, Guojian Cao, Liping Wang, Yuchao Lun, Yicheng Feng
The ultrafine-grained Mg-Nd-Zn-Zr alloy was obtained by an integrated extrusion and equal channel angular pressing at 350 °C with one pass. Microstructural observations showed a significant refinement of grain structure after a single pass extrusion. The average grain size was reduced to around 500 nm. Numerous β1 phases and GP zones were observed in the extruded and subsequently aged alloy. A weak fiber texture with 〈101¯0〉 tilting angle of ∼30° from normal direction towards extrusion direction was found in the extruded alloy. The extruded and subsequently aged alloy presented similar texture to that of the extruded alloy. The extruded alloy exhibited the yield strength (YS), ultimate tensile strength (UTS) and elongation of 248 MPa, 288 MPa and 14.4%, respectively. The extruded alloy after aging treatment achieved higher strength and slightly lower ductility with the YS, UTS and elongation of 264 MPa, 307 MPa and 12.9%, respectively. Compared to the as-cast alloy, the mechanical properties of the extruded and subsequently aged alloy increased 158%, 65% and 34% in YS, UTS and elongation, respectively. The increase in the strength of the extruded and subsequently aged alloy was attributed to both the grain refinement and the precipitation strengthening. The fracture surfaces of the extruded alloy were composed of a lot of small dimples and some cleavage planes. After the aging treatment, the cleavage planes were increased resulting in a decline in the ductility.

Graphical abstract

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Molecularly organic/inorganic hybrid hollow mesoporous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Ping Huang, Yu Chen, Han Lin, Luodan Yu, Linlin Zhang, Liying Wang, Yufang Zhu, Jianlin Shi
Based on the intrinsic features of high stability and unique multifunctionality, inorganic nanoparticles have shown remarkable potentials in combating cancer, but their biodegradability and biocompatibility are still under debate. As a paradigm, this work successfully demonstrates that framework organic-inorganic hybridization can endow the inorganic mesoporous silica nanocarriers with unique tumor-sensitive biodegradability and high biocompatibility. Based on a "chemical homology" mechanism, molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules (HMONs) with high dispersity and sub-50 nm particle dimension were constructed in mass production. A physiologically active disulfide bond (SS) was directly incorporated into the silica framework, which could break up upon contacting the reducing microenvironment of tumor tissue and biodegrade accordingly. Such a tumor-specific biodegradability is also responsible for the tumor-responsive drug releasing by the fast biodegradation and disintegration of the framework. The ultrasmall particle size of HMONs guarantees their high accumulation into tumor tissue, thus causing the high chemotherapeutic outcome. This research provides a paradigm that framework organic-inorganic hybridization can endow the inorganic nanocarrier with unique biological effects suitable for biomedical application, benefiting the development of novel nanosystems with the unique bio-functionality and performance.



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Subconjunctival injectable dendrimer-dexamethasone gel for the treatment of corneal inflammation

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Uri Soiberman, Siva P. Kambhampati, Tony Wu, Manoj K. Mishra, Yumin Oh, Rishi Sharma, Jiangxia Wang, Abdul Elah Al Towerki, Samuel Yiu, Walter J. Stark, Rangaramanujam M. Kannan
Corneal inflammation is often encountered as a key pathological event in many corneal diseases. Current treatments involve topical corticosteroids which require frequent instillations due to rapid tear turnover, causing side-effects such as corneal toxicity and elevated intraocular pressure (IOP). Hence, new interventions that can reduce side effects, dosing frequency, and increase patient compliance can be highly beneficial. In this study, we explore a subconjunctival injectable gel based on G4-PAMAM dendrimer and hyaluronic acid, cross-linked using thiol-ene click chemistry, incorporated with dendrimer dexamethasone (D-Dex) conjugates as a potential strategy for sustained delivery and enhanced bioavailability of corticosteroids. The efficacy of the injectable gel formulation was evaluated in a rat mild alkali burn model. Fluorescently-labelled dendrimers (D-Cy5) incorporated in the gel release D-Cy5 in vivo. The released D-Cy5 selectively targets and localizes within corneal macrophages in inflamed rat cornea but not in healthy controls. This pathology dependent biodistribution was exploited for drug delivery, by incorporating D-Dex in the injectable gel. The attenuation of corneal inflammation by D-Dex gels was assessed using various clinical and biochemical parameters over a 2-week period. Subconjunctival D-Dex gel treatment resulted in favorable clinically-relevant outcomes with reduced central corneal thickness and improved corneal clarity compared to free-Dex and placebo gel controls. The extent of corneal neovascularization was significantly reduced in the D-Dex group. These findings suggest that D-Dex attenuates corneal inflammation more effectively than free-Dex by attenuating macrophage infiltration and pro-inflammatory cytokines expression. A significant elevation in IOP was not observed in the D-Dex group but was observed in the free-Dex group. This novel injectable D-Dex gel may be a potential drug delivery platform for the treatment of many inflammatory ocular surface disorders such as dry eye, auto-immune keratitis and post-surgical complications where frequent steroid administration is required.

Graphical abstract

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Editorial board

Publication date: April 2017
Source:Biomaterials, Volume 124





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A bioinspired elastin-based protein for a cytocompatible underwater adhesive

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): M. Jane Brennan, Bridget F. Kilbride, Jonathan J. Wilker, Julie C. Liu
The development of adhesives that can be applied and create strong bonds underwater is a significant challenge for materials engineering. When the adhesive is intended for biomedical applications, further criteria, such as biocompatibility, must be met. Current biomedical adhesive technologies do not meet these needs. In response, we designed a bioinspired protein system that shows promise to achieve biocompatible underwater adhesion coupled with environmentally responsive behavior that is "smart" – that is, it can be tuned to suit a specific application. The material, ELY16, is constructed from an elastin-like polypeptide (ELP) that can be produced in high yields from Escherichia coli and can coacervate in response to environmental factors such as temperature, pH, and salinity. To confer wet adhesion, we utilized design principles from marine organisms such as mussels and sandcastle worms. When expressed, ELY16 is rich in tyrosine. Upon modification with the tyrosinase enzyme to form mELY16, the tyrosine residues are converted to 3,4-dihydroxyphenylalanine (DOPA). Both ELY16 and mELY16 exhibit cytocompatibility and significant dry adhesion strength (>2 MPa). Modification with DOPA increases protein adsorption to glass and provides moderate adhesion strength (∼240 kPa) in a highly humid environment. Furthermore, this ELP exhibits a tunable phase transition behavior that can be formulated to coacervate in physiological conditions and provides a convenient mechanism for application underwater. Finally, mELY16 possesses significantly higher adhesion strength in dry, humid, and underwater environments compared with a commercially available fibrin sealant. To our knowledge, mELY16 provides the strongest bonds of any rationally designed protein when used completely underwater, and its high yields make it more viable for commercial application compared to natural adhesive proteins. In conclusion, this ELP shows great potential to be a new "smart" underwater adhesive.

Graphical abstract

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Construction of tissue-engineered full-thickness cornea substitute using limbal epithelial cell-like and corneal endothelial cell-like cells derived from human embryonic stem cells

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Canwei Zhang, Liqun Du, Peng Sun, Lin Shen, Jing Zhu, Kunpeng Pang, Xinyi Wu
The aim of this study was to construct a full-thickness artificial cornea substitute in vitro by coculturing limbal epithelial cell-like (LEC-like) cells and corneal endothelial cell-like (CEC-like) cells derived from human embryonic stem cells (hESCs) on APCM scaffold. A 400 μm thickness, 11 mm diameter APCM lamella containing Bowman's membrane was prepared as the scaffold using trephine and a special apparatus made by ourselves. LEC-like cells and CEC-like cells, derived from hESCs as our previously described, were cocultured on the scaffold using a special insert of 24-well plates that enabled seeding both sides of the scaffold. Three or four layers of epithelium-like cells and a uniform monolayer of CEC-like cells could be observed by H&E staining. The thickness, endothelial cell density, and mechanical properties of the construct were similar to that of native rabbit corneas. Immunofluorescence analysis showed expression of ABCG2 and CK3 in the epithelium-like cell layers and expression of N-cadherin, ZO-1 and Na+/K + ATPase in the CEC-like cells. The corneal substitutes were well integrated within the host corneas, and the transparency increased gradually in 8-week follow-up after transplantation in the rabbits. These results suggest that the strategy we developed is feasible and effective for construction of tissue-engineered full-thickness cornea substitute with critical properties of native cornea.



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Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats

Publication date: April 2017
Source:Biomaterials, Volume 124
Author(s): Tobias Peters, Seong-Woo Kim, Vinicius Castro, Krunoslav Stingl, Torsten Strasser, Sylvia Bolz, Ulrich Schraermeyer, George Mihov, MengMeng Zong, Vanessa Andres-Guerrero, Rocio Herrero Vanrell, Aylvin A. Dias, Neil R. Cameron, Eberhart Zrenner
PurposeTo study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated.MethodsForty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8). Electroretinography (ERG), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (sdOCT) were performed at baseline, weeks 1 and 2, and months 1, 2, and 3 after intravitreal injection. Eyes were histologically examined using light microscopy and transmission electron microscopy at the end of the in vivo study.ResultsThere were no statistically significant changes in ERG among the groups. Abnormal FAF pattern and abnormal deposits in OCT were observed after injection but almost completely disappeared between week 2 and month 3 in all injected groups. GFAP staining showed that Müller glia cell activation was most pronounced in PLGA-injected eyes. Increased cell death was not observed by TUNEL staining at month 1. In electron microscopy at month 3, the remnants of microparticles were found in the retinal cells of all injected groups, and loss of plasma membrane was seen in the PLGA group.ConclusionsAlthough morphological changes such as mild glial activation and material remnants were observed histologically 1 month and 3 months after injection in all injected groups, minor cell damage was noted only in the PLGA group at 3 months after injection. No evidence of functional abnormality relative to untreated eyes could be detected by ERG 3 months after injection in all groups. Changes observed in in vivo imaging such as OCT and FAF disappeared after 3 months in almost all cases.



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Epidemiology of basal cell carcinoma: scholarly review

Summary

Basal cell carcinoma (BCC) is the most common cancer in white-skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability-adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR-sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision-making and choose their treatments wisely.

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Adjuvant nodal radiotherapy in the era of sentinel node biopsy staging of breast cancer: a review of published guidelines and prospective trials and their implications on clinical practice

Publication date: Available online 20 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Yazid Belkacemi, Pauline T. Truong, Atif J. Khan, Fady Geara, Alphonse G. Taghian, Meena S. Moran




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Interim 18FDG PET/CT during radiochemotherapy in the management of pelvic malignancies: a systematic review

Publication date: Available online 20 February 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Mahila Ferrari, Laura Travaini, Delia Ciardo, Cristina Garibaldi, Laura Gilardi, Rob Glynne-Jones, Chiara Maria Grana, Barbara Alicja Jereczek-Fossa, Giulia Marvaso, Sara Ronchi, Maria Cristina Leonardi, Roberto Orecchia, Marta Cremonesi
¹⁸F-fluorodeoxyglucose PET/CT (¹⁸F-FDG-PET/CT) is widely applied in oncology for disease staging, assessment of therapy response, relapse diagnosis, follow-up and target volume delineation. In particular, it can detect early response during chemoradiotherapy (interim) because functional modifications usually precede morphological ones. This ability is crucial to the radiation oncologist for the management of patients, to avoid persisting with ineffective therapy − often leading toxicity − and to shift to potentially more effective alternatives.Interim ¹⁸F-FDG-PET imaging in rectal and cervical cancer, the main malignancies of the pelvic district, has been applied and a broad literature is available, although some results are discordant. This systematic review summarizes the application of ¹⁸F-FDG-PET/CT during the chemoradiotherapy of locally advanced pelvic malignancies in order to clarify its capability to predict response and prognosis and its potential role to tailor therapy, which seems to be validated in rectal cancer, whilst less conclusive in cervical cancer.



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Radiofrequency versus Microwave Ablation after Neoadjuvant Transarterial Bland and Drug Eluting Microsphere Chembolization for the Treatment of Hepatocellular Carcinoma

Publication date: Available online 20 February 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Lindsay M. Thornton, Roniel Cabrera, Melissa Kapp, Michael Lazarowicz, Jeff Vogel, Beau Toskich
AimTo retrospectively compare the initial response, local recurrence, and complication rates of radiofrequency ablation (RFA) vs microwave ablation (MWA) when combined with neoadjuvant bland transarterial embolization (TAE) or drug eluting microsphere chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC).MethodsA total of 35 subjects with BCLC very early and early stage HCC (range 1.2–4.1cm) underwent TAE (23) or TACE (12) with RFA (15) or MWA (20) from 1/2009–6/2015 as either definitive therapy or a bridge to transplant. TAE and TACE were performed with 40–400 μm particles and 30–100 μm plus either Doxorubicin or Epirubicin eluting microspheres respectively. Initial response and local progression were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Complications were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.ResultsComplete response (CR) rates were 80% (12/15) for RFA + TAE/TACE and 95% (19/20) for MWA + TAE/TACE (p value 0.29). Local recurrence (LR) was 30% (4/12) for RFA + TAE/TACE and 0% (0/19) for MWA + TAE/TACE. Durability of response (DR), defined as local disease control for duration of the study, demonstrated a significant difference in favor of MWA (p value 0.0091). There was no statistical difference in complication rates (3 vs 2).ConclusionsMWA and RFA when combined with neoadjuvant TAE or TACE have similar safety and efficacy in the treatment of early stage HCC. MWA provided more durable disease control in this study, however, prospective data remains necessary to evaluate superiority of either modality.



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Positive and Negative Signals in Mast Cell Activation

Publication date: Available online 20 February 2017
Source:Trends in Immunology
Author(s): Silvia Bulfone-Paus, Gunnar Nilsson, Petr Draber, Ulrich Blank, Francesca Levi-Schaffer
Mast cells are powerful immune modulators of the tissue microenvironment. Within seconds of activation, these cells release a variety of preformed biologically active products, followed by a wave of mediator synthesis and secretion. Increasing evidence suggests that an intricate network of inhibitory and activating receptors, specific signaling pathways, and adaptor proteins governs mast cell responsiveness to stimuli. Here, we discuss the biological and clinical relevance of negative and positive signaling modalities that control mast cell activation, with an emphasis on novel FcεRI regulators, immunoglobulin E (IgE)-independent pathways [e.g., Mas-related G protein-coupled receptor X2 (MRGPRX2)], tetraspanins, and the CD300 family of inhibitory and activating receptors.



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IL-17 Signaling: The Yin and the Yang

Publication date: Available online 20 February 2017
Source:Trends in Immunology
Author(s): Nilesh Amatya, Abhishek V. Garg, Sarah L. Gaffen
Interleukin (IL)-17 is the founding member of a novel family of inflammatory cytokines. While the proinflammatory properties of IL-17 are key to its host-protective capacity, unrestrained IL-17 signaling is associated with immunopathology, autoimmune disease, and cancer progression. In this review we discuss both the activators and the inhibitors of IL-17 signal transduction, and also the physiological implications of these events. We highlight the surprisingly diverse means by which these regulators control expression of IL-17-dependent inflammatory genes, as well as the major target cells that respond to IL-17 signaling.



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Development of a chronic disease management program for stroke survivors using intervention mapping: The Stroke Coach

Publication date: Available online 20 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brodie M. Sakakibara, Scott A. Lear, Susan I. Barr, Oscar Benavente, Charlie H. Goldsmith, Noah D. Silverberg, Jennifer Yao, Janice J. Eng
ObjectiveTo describe the systematic development of the Stroke Coach, a theory- and evidence-based intervention to improve control of lifestyle behaviour risk factors in stroke patients.DesignIntervention development.SettingCommunity.ParticipantsIndividuals who have had a stroke.InterventionWe used Intervention Mapping to guide the development of the Stroke Coach. Intervention Mapping is a systematic process used for intervention development and comprised of steps that progress from the integration of theory and evidence to the organization of realistic strategies to facilitate the development of a practical intervention supported by empirical evidence. Social Cognitive Theory was the underlying premise for behaviour change, while Control Theory methods were directed towards sustaining the changes to ensure long-term health benefits. Practical evidence-based strategies were linked to behavioural determinants to improve stroke risk factor control.Main outcome measuresNot applicable.ResultsThe Stroke Coach is a patient-centred, community-based, telehealth intervention to promote healthy lifestyles after stroke. Over six months, participants receive seven 30 to 60 minute telephone sessions with a lifestyle coach who provides education, facilitates motivation for lifestyle modification, and empowers participants to self-management their stroke risk factors. Participants also receive a self-management manual and a self-monitoring kit.ConclusionThrough the use of Intervention Mapping we developed a theoretically sound and evidence-grounded intervention to improve risk factor control in stroke patients. If empirical evaluation of the Stroke Coach produces positive results, the next step will be to develop an implementation intervention to ensure successful uptake and delivery of the program in community and outpatient settings.



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Membrane androgen receptor characteristics of human ZIP9 (SLC39A) zinc transporter in prostate cancer cells: Androgen-specific activation and involvement of an inhibitory G protein in zinc and MAP kinase signaling

Publication date: Available online 20 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Peter Thomas, Yefei Pang, Jing Dong
Characteristics of novel human membrane androgen receptor (mAR), ZIP9 (SLC39A9), were investigated in ZIP9-transfected PC-3 cells (PC3-ZIP9). Ligand blot analysis showed plasma membrane [³H]-T binding corresponds to the position of ZIP9 on Western blots which suggests ZIP9 can bind [³H]-T alone, without a protein partner. Progesterone antagonized testosterone actions, blocking increases in zinc, Erk phosphorylation and apoptosis, further evidence that ZIP9 is specifically activated by androgens. Pre-treatment with GTPγS and pertussis toxin decreased plasma membrane [³H]-T binding and blocked testosterone-induced increases in Erk phosphorylation and intracellular zinc, indicating ZIP9 is coupled to an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling. Testosterone treatment of nuclei and mitochondria which express ZIP9 decreased their zinc contents, suggesting ZIP9 also regulates free zinc through releasing it from these intracellular organelles. The results show ZIP9 is a specific Gi coupled-mAR mediating testosterone-induced MAP kinase and zinc signaling in PC3-ZIP9 cells.

Graphical abstract

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Ulipristal acetate administration at mid-cycle changes gene expression profiling of endometrial biopsies taken during the receptive period of the human menstrual cycle

Publication date: Available online 20 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Saúl Lira-Albarrán, Marta Durand, Marco F. Larrea-Schiavon, Leticia González, David Barrera, Claudia Vega, Armando Gamboa-Domínguez, Claudia Rangel, Fernando Larrea
The aim of this study was to analyze the effects of mid-cycle administration of Ulipristal acetate (UPA) on gene expression in endometrial biopsies taken during the receptive phase of the cycle. Fourteen healthy menstruating women were studied during 14 control non-treated and 12 treated cycles with a single dose of 30 mg UPA when follicle diameter reached 20 mm. Ovulation in both treated and control cycles was confirmed by serial determinations of serum LH, progesterone and vaginal ultrasound. An endometrial biopsy at day LH+7, in each cycle, was taken for RNA microarray and qPCR analysis or prepared for histological and immunohistochemistry studies. Functional analysis of differentially expressed genes showed the presence of changes compatible with a non-receptive endometrial phenotype, further confirmed by qPCR and immunohistochemistry. This study suggests the effects of UPA on endometrial receptivity, offering a plausible explanation for the higher contraceptive efficacy of this method compared to that of levonorgestrel.



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Porphyromonas gingivalis lipopolysaccharide induces pro-inflammatory adipokine secretion and oxidative stress by regulating Toll-like receptor-mediated signaling pathways and redox enzymes in adipocytes

Publication date: Available online 20 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Fanny Le Sage, Olivier Meilhac, Marie-Paule Gonthier
Gut microbiota LPS contributes to obesity-related chronic inflammation and oxidative stress, promoting insulin resistance. Periodontal disease also represents a risk factor for type 2 diabetes and is associated with obesity. This study compared the effect of LPS from P. gingivalis periodontopathogen and E. coli enterobacteria on inflammatory adipokine secretion and redox status of 3T3-L1 adipocytes. We found that both LPS activated TLR2- and TLR4-mediated signaling pathways involving MyD88 adaptor and NFκB transcription factor, leading to an increased secretion of leptin, resistin, IL-6 and MCP-1. These effects were partly blocked by inhibitors targeting p38 MAPK, JNK and ERK. Moreover, P. gingivalis LPS reduced adiponectin secretion. Both LPS also enhanced ROS production and the expression of NOX2, NOX4 and iNOS genes. P. gingivalis LPS altered catalase gene expression. Collectively, these results showed that LPS of periodontal bacteria induced pro-inflammatory adipokine secretory profile and oxidative stress in adipocytes which may participate to obesity-related insulin resistance.



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Acute ghrelin changes food preference from high fat diet to chow during binge-like eating in rodents

Abstract

Ghrelin, an orexigenic hormone released from the empty stomach, provides a gut-brain signal that promotes many appetitive behaviors, including anticipatory and goal-directed behaviors for palatable treats high in sugar and/or fat. Here we sought to determine whether ghrelin is able to influence and/or may even have a role in binge-like behavior in rodents. To this end, we used a palatable scheduled feeding (PSF) paradigm in which ad libitum chow-fed rodents are trained to "binge" on high fat diet (HFD) offered each day for a limited period of 2 hr. After 2 weeks of habituation to this paradigm, on the test day and immediately prior to the 2 hr PSF, rats were administered ghrelin or vehicle solution by the intracerebroventricular (ICV) route. Remarkably and unexpectedly, during the palatable scheduled feed, when rats normally only binge on the HFD, those injected with ICV ghrelin started to eat more chow and chow intake remained above baseline for the rest of the 24 hr day. We identify the VTA (a key brain area involved in food reward) as a substrate involved as these effects could be reproduced, in part, by intra-VTA delivery of ghrelin. Fasting, which increases endogenous ghrelin, immediately prior to a palatable schedule feed also increased chow intake during/after the schedule feed but, in contrast to ghrelin injection, did not reduce HFD intake. Chronic continuous central ghrelin infusion over several weeks enhanced binge-like behavior in palatable schedule fed rats. Over a 4 week period, GHS-R1A-KO mice were able to adapt and maintain large meals of HFD in a similar manner as WT mice suggesting that ghrelin signalling may not have a critical role in acquisition or maintenance in this kind of feeding behaviour. In conclusion, ghrelin appears to act as a modulating factor for binge-like eating behaviour by shifting food preference towards a more nutritious choice (from HFD to chow), effects that were somewhat divergent from fasting.

This article is protected by copyright. All rights reserved.

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Views of oral antibiotics and advice seeking about acne: a qualitative study of online discussion forums

Abstract

Background

Acne vulgaris is common and can significantly impair quality of life, yet little is known about patients' understanding of acne and its treatments. Oral antibiotics are widely used for acne, despite concerns about antibiotic resistance. People are increasingly turning to online discussion forums for advice and information on these sites may influence health beliefs and treatment adherence.

Objective

To explore understandings about the use of oral antibiotics for acne and advice shared amongst messages posted on online forums.

Methods

We systematically searched for online forums and identified four where acne was frequently discussed. Discussion threads relating to oral antibiotics were analysed thematically. NVivo 11 facilitated data handling.

Results

We extracted 136 pages of data; 65 discussions amongst 294 participants. We found a wide range of perceptions around effectiveness of antibiotics for acne and concerns about adverse effects. The delayed onset of action of antibiotics was a source of frustration and compounded dissatisfaction with healthcare providers, who people perceived as 'fobbing them off' with prolonged courses of ineffective treatment. Advice ranged from costly cleansers to when to ask for, or insist on, referral. Posts related to a wide range of severities, from 'spots' to severe acne, which may make it confusing for users to assess appropriateness of information.

Conclusions

Online forums offer opinions that could be confusing or lead to early abandonment of treatments, challenging consultations and patient dissatisfaction. Users expressed frustration about the delayed onset of action of antibiotics for acne, perceptions of only temporary effectiveness and adverse effects.

This article is protected by copyright. All rights reserved.

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Caring for children with intellectual disabilities part 2: Detailed analyses of factors involved in respite workers’ reported assessment and care decisions

Publication date: April 2017
Source:Research in Developmental Disabilities, Volume 63
Author(s): Lara M. Genik, C. Meghan McMurtry, Lynn M. Breau
Respite workers (RW) commonly care for children with intellectual disabilities (ID), and pain is common for these children. Little is known about factors which inform RW pain assessment and management-related decisions.ObjectivesTo describe/determine the following in response to a series of pain-related scenarios (e.g., headache, falling): (1) factors considered important by RW when assessing children with ID's pain; (2) whether children's verbal ability impacts pain assessment factors considered; (3) RW assessment and management approach.ParticipantsFifty-six RW (18–67 years, Mage=33.37, 46 female).Procedure/measuresIn an online survey, participants read and responded to six vignettes manipulating child verbal ability (verbal, nonverbal) and pain source.ResultsThe factors most frequently considered when assessing pain were child behavior (range: 20–57.4%), and history (e.g., pain, general; 3.7–38.9%). Factors did not vary by child's verbal ability. RW indicated varied assessment and management-related actions (range: 1–11) for each scenario.DiscussionFindings suggest: a) factors informing pain assessment did not depend on whether or not the child was verbal and b) a degree of flexibility in RW response to pain across situations. While these findings are encouraging, ensuring RW have adequate pain assessment and management knowledge specific to children with ID is critical.



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The Impact of Oral Health on General Health: Educating Professionals and Patients

Abstract

Purpose of Review

This review provides a brief summary of what science has postulated about the oral cavity and its relationship to the rest of the body. This article then looks at the emerging body of evidence for a definitive statement on the impact of oral health and disease on overall health and disease. It concludes by examining ways to educate oral healthcare providers (OHCPs) (i.e., dentists and dental hygienists) and their role in educating patients and the public about the interrelationships of oral and overall health and challenges associated with this.

Recent Findings

Since 1989, there have been major advances in understanding the role of periodontal infection and inflammation in contributing to the risk for systemic diseases. As the evidence emerges for an oral-systemic link, new strategies for educating dentistry, medicine, other non-dental healthcare professions, and the public about this link are also emerging.

Summary

Hopefully, a new awareness and understanding of the significance of oral health in sustaining general health lead to a new emphasis for prevention and treatment of periodontal disease.

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2-Methoxyestradiol protects against IgG immune complex-induced acute lung injury by blocking NF-κB and CCAAT/enhancer-binding protein β activities

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Chunguang Yan, Yanfei Shen, Qiqing Sun, Dong Yuan, Huifang Tang, Hongwei Gao
Increasing evidences indicate that 2-Methoxyestradiol (2ME2) plays an essential role in protecting against inflammatory responses. However, its effect on IgG immune complex (IC)-induced acute lung injury (ALI) remains enigmatic. In the study, by using i.p. administration of 2ME2, we evaluated its influence on IgG IC-induced pulmonary injury in mice. We found that during IgG IC-induced ALI, mice treated by 2ME2 displayed a substantial decrease in vascular permeability and neutrophil influx (represented by myeloperoxidase activity) when compared with their counterparts receiving vehicle treatment. Furthermore, 2ME2 treatment significantly decreased pro-inflammatory mediator production and inflammatory cell, especially neutrophil accumulation in bronchoalveolar lavage fluids (BALFs) upon IgG IC stimulation. In vitro, IgG IC-triggered inflammatory mediator production was markedly down-regulated by 2ME2 in macrophages. Moreover, we verified that the activation of the transcription factors, NF-κB and CCAAT/enhancer-binding protein (C/EBP) β, were inhibited by 2ME2 in IgG IC-challenged macrophages. We demonstrated that alleviation of NF-κB-dependent transcription might be associated with reduced phosphorylation of NF-κB p65, and reduction of C/EBP activation was directly linked to its expression. In addition, we discovered that IgG IC-stimulated phosphorylation of both p38 MAPK and ERK1/2 was alleviated by 2ME2. These data indicated a novel strategy for blockade of IgG IC-induced inflammatory activities.



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Inflammatory chemokines and their receptors in human visceral leishmaniasis: Gene expression profile in peripheral blood, splenic cellular sources and their impact on trafficking of inflammatory cells

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Neetu Singh, Shyam Sundar
Chemokines play an important role in determining cellular composition at inflammatory sites, and as such, influence disease outcome. In this study, we investigated the expression profile and splenic cellular source of various inflammatory chemokines and their receptors in human visceral leishmaniasis (VL). The expression of chemokines or their receptors was measured at the gene and protein level by employing real time qPCR and a cytometric bead array assay, respectively. In addition, the cellular source of chemokines and their receptors in the spleen was identified employing gene expression analyses in sequentially selected cell subsets. We identified elevated expression of CXCL10, CXCL9, CXCL8, and decreased CCL2 from VL patients. Further, we found reduced expression of the chemokine receptors CXCR1, CXCR2, CXCR3 and CCR2, but increased expression of CCR7 on VL PBMC, compared to endemic healthy controls. Additionally, splenic monocytes were found to be the major source of CXCL10, CXCL9 and CCR2, whereas T cells were the main source of CXCR3 and CCR7. We also report a strong association between plasma IFN-γ and CXCL-10, CXCL-9 levels. Enhanced parasite burden positively correlates with increased expression of CXCL10, CXCL9, IFN-γ and IL-10. Overall our result indicates that VL patients have an elevated inflammatory chemokine milieu which correlated with disease severity. However, expression of their chemokine receptors was significantly impaired, which may have contributed to reduced frequencies of blood monocytes and neutrophils in peripheral blood. In contrast, enhanced expression of CCR7 was associated with increased numbers of activated T cells in circulation. These findings highlight the importance of chemokines for recruitment of various cell populations in VL, and the knowledge gained may help in global understandings of the complex interaction between chemokines and pathological processes, and therefore will contribute towards the design of novel chemokine based immunological therapies against VL.

Graphical abstract

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Hereditary C1 inhibitor deficiency is associated with high spontaneous amidase activity

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Delphine Charignon, Arije Ghannam, Denise Ponard, Christian Drouet
BackgroundAngioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function and antigenic C4 level) and contact phase activation (via amidase activity). Bradykinin is responsible for angioedema attacks and is produced from contact phase activation secondary to failed C1Inh control.ObjectiveWe aimed to compare the diagnostic performances of spontaneous amidase activity and antigenic C4 level in C1Inh hereditary angioedema (C1Inh-HAE) patients.MethodsSamples from 185 C1Inh-HAE patients (81 men, 104 women; confirmed by SERPING1 gene mutations) and from 99 blood donors (50 men, 49 women) were tested for C1Inh function, antigenic C4 level and spontaneous amidase activity.ResultsIn the C1Inh-HAE group, antigenic C4 level was decreased (n=135) and amidase activity was increased (n=181). Receiver operating characteristic analyses showed higher diagnostic performance values for the spontaneous amidase assay compared to those of antigenic C4.ConclusionThe spontaneous amidase activity assay should replace antigenic C4 level testing and should be tested alongside the C1Inh function for both AE screening and follow up of HAE patients.



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International Recommendations for Electrocardiographic Interpretation in Athletes

Abstract

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural, or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly over the last decade; pushed by a growing body of scientific data that both tests proposed criteria sets and establishes new evidence to guide refinements. On February 26-27, 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington, to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.

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Reply: Heart Rate Reduction and Cardiovascular Outcome in Hypertension

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