Cross platform standardisation and normalisation experimental pipeline for use in the biodiscovery of dysregulated human circulating miRNAs

Introduction. Micro RNAs (miRNAs) are a class of highly conserved small non-coding RNAs that play an important part in the post-transcriptional regulation of gene expression. A substantial number of miRNAs have been proposed as biomarkers for diseases. While reverse transcriptase Real-time PCR (RT-qPCR) is considered the gold standard for the evaluation and validation of miRNA biomarkers, small RNA sequencing is now routinely being adopted for the identification of dysregulated miRNAs. However, in many cases where putative miRNA biomarkers are identified using small RNA sequencing, they are not substantiated when RT-qPCR is used for validation. To date, there is a lack of consensus regarding optimal methodologies for miRNA detection, quantification and standardisation when different platform technologies are used. Materials and Methods. In this study we present an experimental pipeline that takes into consideration sample collection, processing, enrichment, and the subsequent comparative analysis of circulating small ribonucleic acids using small RNA sequencing and RT-qPCR. Results, Discussion, Conclusions Initially, a panel of miRNAs dysregulated in circulating blood from breast cancer patients compared to healthy women were identified using small RNA sequencing. MiR-320a was identified as the most dysregulated miRNA between the two female cohorts. Total RNA and enriched small RNA populations (<30 bp) isolated from peripheral blood from the same female cohort samples were then tested for using a miR-320a RT-qPCR assay. When total RNA was analysed with this miR-320a RT-qPCR assay, a 2.3-fold decrease in expression levels was observed between blood samples from healthy controls and breast cancer patients. However, upon enrichment for the small RNA population and subsequent analysis of miR-320a using RT-qPCR, its dysregulation in breast cancer patients was more pronounced with an 8.89-fold decrease in miR-320a expression. We propose that the experimental pipeline outlined could serve as a robust approach for the identification and validation of small RNA biomarkers for disease

Intravenous versus subcutaneous drug administration. Which do patients prefer? A systematic review

BACKGROUND: Intravenous (IV) drug delivery is commonly used for its rapid administration and immediate drug effect. Most studies compare IV to subcutaneous (SC) delivery in terms of safety and efficacy, but little is known about what patients prefer. METHODS: A systematic review was conducted by searching seven electronic databases for articles published up to February 2014. Included studies were randomized controlled trials (RCTs) and/or crossover designs investigating patient preference for SC versus IV administration. The risk of bias in the RCTs was determined using the Cochrane Collaboration tool. Reviewers independently extracted data and assessed the risk of bias. Any discrepancies were resolved by consensus. RESULTS: The search identified 115 publications, but few (6/115) met the inclusion criteria. Patient populations and drugs investigated were diverse. Four of six studies demonstrated a clear patient preference for SC administration. Main factors associated with SC preference were time saving and the ability to have treatment at home. Only three studies used study-specific instruments to measure preference. CONCLUSIONS: Results suggest that patients prefer SC over IV delivery. Patient preference has clearly been neglected in clinical research, but it is important in medical decision making when choosing treatment methods as it has implications for adherence and quality of life. If the safety and efficacy of both administration routes are equivalent, then the most important factor should be patient preference as this will ensure optimal treatment adherence and ultimately improve patient experience or satisfaction. Future drug efficacy and safety studies should include contemporaneous, actual patient preference where possible, utilizing appropriate measures

Capillary processes increase salt precipitation during CO2 injection in saline formations

An important attraction of saline formations for CO2 storage is that their high salinity renders their associated brine unlikely to be identified as a potential water resource in the future. However, high salinity can lead to dissolved salt precipitating around injection wells, resulting in loss of injectivity and well deterioration. Earlier numerical simulations have revealed that salt precipitation becomes more problematic at lower injection rates. This article presents a new similarity solution, which is used to study the relationship between capillary pressure and salt precipitation around CO2 injection wells in saline formations. Mathematical analysis reveals that the process is strongly controlled by a dimensionless capillary number, which represents the ratio of the CO2 injection rate to the product of the CO2 mobility and air-entry pressure of the porous medium. Low injection rates lead to low capillary numbers, which in turn are found to lead to large volume fractions of precipitated salt around the injection well. For one example studied, reducing the CO2 injection rate by 94 % led to a tenfold increase in the volume fraction of precipitated salt around the injection well

Pioneers across war zones: The lived acculturation experiences of US female military expatriates

This exploratory study focuses on the lived acculturation experiences of United States (US) female career military expatriates who worked and lived in combat settings across five war zones. Based on an analysis of oral histories that spanned over 60 years, the research revealed that these pioneering women had a strong commitment to their profession, and that this, along with camaraderie, facilitated their adaptation to living conditions characterized by extreme danger, nominal domestic comforts, and unrelenting work requirements in culturally unfamiliar contexts. The research identified the multiple physical and psychological stressors of living and working as a female in a war zone and the variety of coping strategies employed for acculturation, particularly the prominent role of relational support from family and friends, and a combination of personal coping mechanisms (such as crying or compartmentalization) and religious faith. As extant expatriate research has overwhelmingly focused on male executives in multinational corporations, this research is significant in extending the literature to an analysis of the public sector, specifically women deployed overseas in highly dangerous settings and who were pioneering in both their roles in the military and as non-traditional expatriates at a time when few women worked internationally

Use of antidepressants and potential drug interactions in cancer patients treated at a hospital in the Southern Brazil

Justificativa e Objetivos: O câncer é uma doença crônico-degenerativa e seu diagnóstico muitas vezes está associado a sofrimento mental, dúvidas e inseguranças podendo desencadear o aparecimento de sintomas depressivos. Frequentemente, são necessárias medidas farmacológicas para o tratamento destes sintomas. Entretanto, pacientes oncológicos frequentemente utilizam vários medicamentos (polifarmácia) aumentando assim as chances de potencias interações medicamentosas (IM). O objetivo deste estudo foi avaliar o uso de antidepressivos nos pacientes em tratamento oncológico hospitalizados e as potenciais IM presentes nas prescrições destes pacientes. Métodos: Estudo transversal, prospectivo, descritivo e analítico realizado com pacientes oncológicos com idade ≥ 18 anos, internados em um hospital do sul do Brasil, e cientes de seu diagnóstico. As interações medicamentosas, maiores e contraindicadas, foram analisadas usando as bases de dados Micromedex® e Lexicomp®. Resultados: A amostra foi de 50 pacientes, 54% eram do gênero feminino e a média de idade foi 53,6 (±15,3) anos. Utilizavam medicamentos antidepressivos 42% dos pacientes, sendo o escitalopram (Inibidor Seletivo Recaptação Serotonina) o mais prescrito. Apresentaram algum tipo de potencial interação 90% dos pacientes e estas ocorreram com quaisquer medicamento prescrito ao tratamento. Dos pacientes que utilizavam antidepressivos, 62% apresentaram interações contraindicadas e todos apresentaram pelo menos um caso de interação maior. Os medicamentos mais relacionados a interações medicamentosas contraindicadas foram a dipirona e a metoclopramida. Conclusão: Os resultados deste estudo demonstraram um elevado número de IM contraindicadas envolvendo medicamentos antidepressivos. Neste contexto, verifica-se a importância do farmacêutico clínico na monitorização da farmacoterapia destes pacientes

Significance of beach geomorphology on fecal indicator bacteria levels

© The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 121 (2017): 160-167, doi:10.1016/j.marpolbul.2017.05.024.Large databases of fecal indicator bacteria (FIB) measurements are available for coastal waters. With the assistance of satellite imagery, we illustrated the power of assessing data for many sites by evaluating beach features such as geomorphology, distance from rivers and canals, presence of piers and causeways, and degree of urbanization coupled with the enterococci FIB database for the state of Florida. We found that beach geomorphology was the primary characteristic associated with enterococci levels that exceeded regulatory guidelines. Beaches in close proximity to marshes or within bays had higher enterococci exceedances in comparison to open coast beaches. For open coast beaches, greater enterococci exceedances were associated with nearby rivers and higher levels of urbanization. Piers and causeways had a minimal contribution, as their effect was often overwhelmed by beach geomorphology. Results can be used to understand the potential causes of elevated enterococci levels and to promote public health.The early portion of this work was funded in part by the NSF–NIEHS Oceans and Human Health Program (NIEHS #P50 ES12736 and NSF #OCE0432368/0911373/1127813)

Assessment of Imagining and Material Characteristics of a Radiopaque, Thermoresponsive Hydrogel for Intratumoral Administration to Solid Tumours

Introduction Thermoresponsive hydrogels are gels which have different properties at varying temperatures. The objective of this study was to assess the material characteristics, imaging properties and chemotherapeutic drug release profile of a novel radiopaque thermoresponsive hydrogel, which is liquid at room temperature but solidifies at body temperature, to determine potential suitability for intratumoral delivery. Materials and Methods An iodinated radiopaque thermoresponsive hydrogel was formulated using iodixanol at a range of concentrations and assessed for sol-gel transition, radiopacity and imaging using CT and US. A lead formulation containing 9.22% w/w iodixanol was evaluated for injectability, disintegration and dual drug release of cisplatin and paclitaxel from the hydrogel formulation. Results Radiopacity of the hydrogel increased in a concentration dependent manner but higher concentrations of iodixanol adversely affected the sol-gel transition of the hydrogel, therefore 9.22%w/w iodixanol hydrogel was identified as the lead formulation. This formulation was readily visible on both CT and US. The formulation was hand-injectable through a range of clinically relevant devices, had a sustained disintegration profile for up to 28 days, and was able to deliver a sustained release of chemotherapeutic drug for up to 10 days. Discussion Favourable imaging and material characteristics of this thermoresponsive gel are demonstrated, suggesting potential interventional oncology applications for image-guided intratumoral delivery of sustained-release chemotherapy

Wave energy level and geographic setting correlate with Florida beach water quality

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 104 (2016): 54-60, doi:10.1016/j.marpolbul.2016.02.011.Many recreational beaches suffer from elevated levels of microorganisms, resulting in beach advisories and closures due to lack of compliance with Environmental Protection Agency guidelines. We conducted the first statewide beach water quality assessment by analyzing decadal records of fecal indicator bacteria (enterococci and fecal coliform) levels at 262 Florida beaches. The objectives were to depict synoptic patterns of beach water quality exceedance along the entire Florida shoreline and to evaluate their relationships with wave condition and geographic location. Percent exceedances based on enterococci and fecal coliform were negatively correlated with both long-term mean wave energy and beach slope. Also, Gulf of Mexico beaches exceeded the thresholds significantly more than Atlantic Ocean ones, perhaps partially due to the lower wave energy. A possible linkage between wave energy level and water quality is beach sand, a pervasive nonpoint source that tends to harbor more bacteria in the low-wave-energy environment.This work is funded by the NSF-NIEHS Oceans and Human Health Program (NIEHS # P50 ES12736 and NSF #OCE0432368/0911373/1127813)