Ratiometric array of conjugated polymers–fluorescent protein provides a robust mammalian cell sensor

© 2016 American Chemical Society.Supramolecular complexes of a family of positively charged conjugated polymers (CPs) and green fluorescent protein (GFP) create a fluorescence resonance energy transfer (FRET)-based ratiometric biosensor array. Selective multivalent interactions of the CPs with mammalian cell surfaces caused differential change in FRET signals, providing a fingerprint signature for each cell type. The resulting fluorescence signatures allowed the identification of 16 different cell types and discrimination between healthy, cancerous, and metastatic cells, with the same genetic background. While the CP-GFP sensor array completely differentiated between the cell types, only partial classification was achieved for the CPs alone, validating the effectiveness of the ratiometric sensor. The utility of the biosensor was further demonstrated in the detection of blinded unknown samples, where 121 of 128 samples were correctly identified. Notably, this selectivity-based sensor stratified diverse cell types in minutes, using only 2000 cells, without requiring specific biomarkers or cell labeling

Investigation of occupational and environmental causes of respiratory cancers (ICARE): a multicenter, population-based case-control study in France

<p>Abstract</p> <p>Background</p> <p>Occupational causes of respiratory cancers need to be further investigated: the role of occupational exposures in the aetiology of head and neck cancers remains largely unknown, and there are still substantial uncertainties for a number of suspected lung carcinogens. The main objective of the study is to examine occupational risk factors for lung and head and neck cancers.</p> <p>Methods/design</p> <p>ICARE is a multi-center, population-based case-control study, which included a group of 2926 lung cancer cases, a group of 2415 head and neck cancer cases, and a common control group of 3555 subjects. Incident cases were identified in collaboration with cancer registries, in 10 geographical areas. The control group was a random sample of the population of these areas, with a distribution by sex and age comparable to that of the cases, and a distribution by socioeconomic status comparable to that of the population. Subjects were interviewed face to face, using a standardized questionnaire collecting particularly information on tobacco and alcohol consumption, residential history and a detailed description of occupational history. Biological samples were also collected from study subjects. The main occupational exposures of interest are asbestos, man-made mineral fibers, formaldehyde, polycyclic aromatic hydrocarbons, chromium and nickel compounds, arsenic, wood dust, textile dust, solvents, strong acids, cutting fluids, silica, diesel fumes, welding fumes. The complete list of exposures of interest includes more than 60 substances. Occupational exposure assessment will use several complementary methods: case-by-case evaluation of exposure by experts; development and use of algorithms to assess exposure from the questionnaires; application of job-exposure matrices.</p> <p>Discussion</p> <p>The large number of subjects should allow to uncover exposures associated with moderate increase in risks, and to evaluate risks associated with infrequent or widely dispersed exposures. It will be possible to study joint effects of exposure to different occupational risk factors, to examine the interactions between occupational exposures, tobacco smoking, alcohol drinking, and genetic risk factors, and to estimate the proportion of respiratory cancers attributable to occupational exposures in France. In addition, information on many non-occupational risk factors is available, and the study will provide an excellent framework for numerous studies in various fields.</p

Severe Airway Epithelial Injury, Aberrant Repair and Bronchiolitis Obliterans Develops after Diacetyl Instillation in Rats

Bronchiolitis obliterans (BO) is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA), a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1) to determine if DA, delivered by intratracheal instillation (ITI), would lead to the development of BO in rats and 2) to characterize epithelial regeneration and matrix repair after ITI of DA.Male Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg) or sterile water (vehicle control) by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions.We have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation–Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials

Purpose: To report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector–based gene therapy for RPE65 mutation–associated inherited retinal dystrophy (IRD), including results of a phase 1 follow-on study at year 4 and phase 3 study at year 2. Design: Open-label phase 1 follow-on clinical trial and open-label, randomized, controlled phase 3 clinical trial. Participants: Forty subjects who received 1.5×1011 vector genomes (vg) of VN per eye in at least 1 eye during the trials, including 11 phase 1 follow-on subjects and 29 phase 3 subjects (20 original intervention [OI] and 9 control/intervention [CI]). Methods: Subretinal injection of VN in the second eye of phase 1 follow-on subjects and in both eyes of phase 3 subjects. Main Outcome Measures: End points common to the phase 1 and phase 3 studies included change in performance on the Multi-Luminance Mobility Test (MLMT) within the illuminance range evaluated, full-field light sensitivity threshold (FST) testing, and best-corrected visual acuity (BCVA). Safety end points included adverse event reporting, ophthalmic examination, physical examination, and laboratory testing. Results: Mean (standard deviation) MLMT lux score change was 2.4 (1.3) at 4 years compared with 2.6 (1.6) at 1 year after administration in phase 1 follow-on subjects (n = 8), 1.9 (1.1) at 2 years, and 1.9 (1.0) at 1 year post-administration in OI subjects (n = 20), and 2.1 (1.6) at 1 year post-administration in CI subjects (n = 9). All 3 groups maintained an average improvement in FST, reflecting more than a 2 log10(cd.s/m2) improvement in light sensitivity at 1 year and subsequent available follow-up visits. The safety profile was consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred. Conclusions: After VN gene augmentation therapy, there was a favorable benefit-to-risk profile with similar improvement demonstrated in navigational ability and light sensitivity among 3 groups of subjects with RPE65 mutation–associated IRD, a degenerative disease that progresses to complete blindness. The safety profile is consistent with the administration procedure. These data suggest that this effect, which is nearly maximal by 30 days after VN administration, is durable for 4 years, with observation ongoing

Stakeholders’ Perspective on Groundwater Management in Four Water-Stressed Mediterranean Areas: Priorities and Challenges

Recent studies highlight the fragility of the Mediterranean basin against climate stresses and the difficulties of managing the sustainable development of groundwater resources. In this work, the main issues related to groundwater management have been identified from the stake-holder’s perspective in the following four representative water-stressed Mediterranean areas: the coastal aquifer of Comacchio (Italy), the Alto Guadalentín aquifer (Spain), the alluvial aquifer of the Gediz River basin (Turkey), and the Azraq aquifer (Azraq Wetland Reserve, Jordan). This has been achieved by designing a methodology to involve and engage a representative set of stakeholders, including a questionnaire to learn their point of view concerning the current management of aquifer systems and their experience with the already available tools for groundwater resource manage-ment, such as monitoring networks and numerical models. The outcome of the survey has allowed us to identify both particular and common challenges among the four study sites and among the various groups of stakeholders. This information provides valuable insights to improve the transfer of scientific knowledge from the research centers to the authorities managing the groundwater resources and it will help to plan more effective research activities on aquifer management. The proposed methodology could be applied in other aquifers facing similar problems

Analgesia e sedação durante a instalação do cateter central de inserção periférica em neonatos

Objetivou-se caracterizar as estratégias de analgesia e sedação em neonatos submetidos à instalação do cateter central de inserção periférica (CCIP) e relacioná-las ao número de punções venosas, duração do procedimento e posicionamento da ponta do cateter. Estudo transversal com coleta prospectiva de dados, realizado em uma unidade de cuidados intensivos neonatais de um hospital privado na cidade de São Paulo, no período de 31 de agosto de 2010 a 01 de julho de 2011, em que foram avaliadas 254 inserções do CCIP. A adoção de estratégias analgésicas ou sedativas ocorreu em 88 (34,6%) instalações do cateter e não esteve relacionada ao número de punções venosas, duração do procedimento ou posicionamento da ponta do cateter. As estratégias mais frequentes foram a administração endovenosa de midazolam em 47 (18,5%) e fentanil em 19 (7,3%) inserções do cateter. Recomenda-se maior adoção de estratégias analgésicas antes, durante e após o procedimento

Faktori rizika od karcinoma larinksa u Crnoj Gori

Laryngeal cancer is the most common head and neck cancer. There might be many risk factors for laryngeal cancer. Smoking, especially cigarette smoking and alcohol are indisputable risk factors. The authors of this paper assessed the presumed risk factors in order to identify possible aetiological agents of the disease. A hospital-based case-control study was conducted. The study group consisted of 108 histologically verified laryngeal cancer patients and 108 hospital controls matched by sex, age (±3 years) and place of residence. Laryngeal cancer patients and controls were interviewed during their hospital stay using a structured questionnaire. According to multiple logistic regression analysis six variables were independently related to laryngeal cancer: hard liquor consumption (Odd Ratio /OR/=2.93, Confidence Interval /CI/ 95 % = 1.17 to 7.31), consumption more than 2 alcoholic drinks per day (OR=4.96, CI 95 % = 2.04 to12.04), cigarette smoking for more than 40 years (OR=4.32, CI 95 % = 1.69 to 11.06), smoking more than 30 cigarettes per day (OR=4.24, CI 95 % = 1.75 to 10.27), coffee consumption more than 5 cups per day (OR=4.52, CI 95 % = 1.01 to 20.12) and carbonated beverage consumption (OR=0.38, CI 95 %= 0.16 to 0.92). The great majority of laryngeal cancers could be prevented by eliminating tobacco smoking and alcohol consumption.Maligni tumori larinksa najčešći su tumori glave i vrata. Glavni faktori rizika od razvoja malignih tumora grkljana su pušenje i konzumiranje alkoholnih pića. Cilj rada bio je ispitivanje potencijalnih faktora rizika od nastanka malignih tumora larinksa. Sprovedena je studija slučaj-kontrola. Studijsku grupu činilo je 108 pacijenata s histološki verificiranim rakom larinksa i 108 kontrola individualno izjednačenih po spolu, dobi (± 3 godine) i mjestu stanovanja. Svi ispitanici su anketirani ciljanim epidemiološkim upitnikom a u analizi podataka korištena je multivarijantna logistička regresijska analiza. Koristeći se multivarijantnom logističkom regresijskom analizom, statistički značajnu povezanost s rakom larinksa dobili smo za sljedeće varijable: konzumiranje žestokih pića (omjer izgleda /OR/=2.93, interval pouzdanosti /CI/ 95 % = 1.17 do 7.31), konzumiranje više od 2 alkoholna pića na dan (OR = 4.96, CI 95 % = 2.04 do 12.04), konzumiranje cigareta duže od 40 godina (OR = 4.32, CI 95 % = 1.69 do 11.06), konzumiranje više od 30 cigareta na dan (OR = 4.24, CI 95 % = 1.75 do 10.27), konzumiranje više od 5 šalica kave na dan (OR = 4.52, CI 95 % = 1.01 do 20.12) i konzumiranje gaziranih pića (OR = 0.38, CI 95 % = 0.16 do 0.92). Obolijevanje zbog malignih tumora larinksa moglo bi se značajno smanjiti prestankom konzumiranja duhana i alkohola

SMART trial: A randomized clinical trial of self-monitoring in behavioral weight management-design and baseline findings.

BACKGROUND: The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial. METHODS: The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA + FB). RESULTS: We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24 months, retention rate for the first of three cohorts was 90%. CONCLUSIONS: To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component

Essential Medicines at the National Level : The Global Asthma Network's Essential Asthma Medicines Survey 2014

Patients with asthma need uninterrupted supplies of affordable, quality-assured essential medicines. However, access in many low- and middle-income countries (LMICs) is limited. The World Health Organization (WHO) Non-Communicable Disease (NCD) Global Action Plan 2013-2020 sets an 80% target for essential NCD medicines' availability. Poor access is partly due to medicines not being included on the national Essential Medicines Lists (EML) and/or National Reimbursement Lists (NRL) which guide the provision of free/subsidised medicines. We aimed to determine how many countries have essential asthma medicines on their EML and NRL, which essential asthma medicines, and whether surveys might monitor progress. A cross-sectional survey in 2013-2015 of Global Asthma Network principal investigators generated 111/120 (93%) responses41 high-income countries and territories (HICs); 70 LMICs. Patients in HICs with NRL are best served (91% HICs included ICS (inhaled corticosteroids) and salbutamol). Patients in the 24 (34%) LMICs with no NRL and the 14 (30%) LMICs with an NRL, however no ICS are likely to have very poor access to affordable, quality-assured ICS. Many LMICs do not have essential asthma medicines on their EML or NRL. Technical guidance and advocacy for policy change is required. Improving access to these medicines will improve the health system's capacity to address NCDs.Peer reviewe