The Application of Electrosprayed Minocycline-Loaded PLGA For The Treatment Of Glioblastoma

Background: Glioblastoma multiforme (GBM) is one of the most common and aggressive forms of cancer with unfavorable prognosis due to high levels of reoccurrence with around 10,000 patients in the U.S. diagnosed each year. Despite treatment with surgery, radiotherapy, and chemotherapy, survival rate for this disease is around 21 months after diagnosis. Minocycline, a tetracycline-derivative used as an antibiotic, has also demonstrated the ability to inhibit angiogenesis or tumor growth and, presents a possible treatment option for GBM. Methods: Microparticles were fabricated by electrospraying by varying solvent type, distance, flow rate, voltage, and polymer concentration as parameters. The cytotoxicity of endothelial and glioblastoma cells was determined by an MTT assay by determining the absorbance using a spectrophotometer at a wavelength of 350 nm. Scanning electron microscopy (SEM) imaging was used to image the samples to determine microparticle surface morphology and size via an electron beam due to microparticles being sputter coated with gold to generate an electrical conduction. Results: The electrospraying process consists of numerous parameters which directly affect the creation of microparticles. The use of the solvent methanol aids in dissolving minocycline, while the use of DCM is important for the process of electrospraying, due to its higher vapor pressure and ability to dissolve PLGA. Conclusion: In conclusion, electrospraying is a promising method to fabricate drug loaded PLGA microparticles. However, optimization is needed whenever there is a new drug of interest as it can modify the properties of the electrospray solution and result in different effects on the fabrication parameters and particles produced

Pharmacists and Pharmacogenomics: An Evaluation of Knowledge, Beliefs, Attitudes and Practices

Pharmacogenomics is the term used to describe the rapidly advancing study on how genetic makeup can impact drug therapy. In specialized clinical situations, such as the use of irinotecan in colon cancer or abacavir in HIV infections, it is now possible to identify specific genotypes that correlate strongly with a patient\u27s therapeutic outcome, with implications on both efficacy and side effects. On a broader scale, a systematic review published by the Journal of the American Medical Association on the top 27 adverse reaction-causing drugs found that a majority of the adverse effects have a genetic component, suggesting that an analysis of an individual\u27s genetic profile may help in the management of these adverse drug reactions. Additionally, the FDA has included genetic information on more than 100 drug labels. The more that is understood about the association between genotype and drug response, the greater the opportunity and responsibility will be for pharmacists in this realm

Temporal trends in pregnancy-associated stroke and its outcomes among women with hypertensive disorders of pregnancy

Funding PW is funded by a NIHR Transitional Research Fellowship. CCG is part-funded by West Midlands ARC. LCC is funded by a NIHR Professorship (RP-2014-05-019). This paper presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no involvement in the conduct of this research.Peer reviewedPublisher PD

The Association between Loneliness with Increased Mental Health Problems and Substance Use During the COVID-19 Pandemic in Richmond, Virginia

Background. The COVID-19 pandemic caused significant psychological distress among U.S. adults leading to increased rates of adverse mental health symptoms and substance use. This study aims to evaluate the consistency of the association between loneliness and increased mental health problems and substance use in Richmond, VA during the COVID-19 pandemic. Methods. Data were collected in two phases: 1) internet-based surveys from August 2020 to March 2021 (N=327) and 2) paper-pencil surveys from May to October 2021 (N=225). Logistic regression was used to test the association between loneliness and increased mental health and substance use, while adjusting for sociodemographic factors and pre-existing mental health conditions. Results. Both survey populations reported a high prevalence of increased loneliness (46.7% - 68.8%), mental health problems (50.2% - 67.3%), and substance use (22.2% - 29.4%) since the COVID-19 pandemic. Increased loneliness since the pandemic was significantly associated with increased mental health problems (Online survey: AOR=5.00, 95% CI=2.56 - 9.97; Paper-pencil survey: AOR=10.48, 95% CI=4.18 - 28.59) and increased substance use (Online survey: AOR=3.14, 95% CI=1.58 - 6.60; Paper-pencil survey: AOR=5.89, 95% CI=1.97 - 19.71). Conclusions. The association between increased loneliness and increased mental health problems and substance use during COVID-19 in Richmond, Virginia was consistent across the two survey populations and similar to the rest of the U.S

Pandemic (H1N1) 2009 Surveillance and Prevalence of Seasonal Influenza, Singapore

On April 25, 2009, Singapore implemented strict containment measures for pandemic (H1N1) 2009 with enhanced surveillance and hospital isolation. In the first month, seasonal influenza, predominantly virus subtype H3N2, was diagnosed for 32% of patients with acute febrile respiratory illness. Our findings underscore the high prevalence of seasonal influenza in Singapore

Using reflexivity to enhance in-depth interviewing skills for the clinician researcher

<p>Abstract</p> <p>Background</p> <p>Primary health care clinicians are being encouraged to undertake qualitative research, however the in-depth interviewing skills required are not as straightforward as might be first supposed. While there are benefits and certain skills that clinicians can bring to interview-based research, there are important new skills to develop. To date there has been neither discussion about these new skills, nor any preparatory guidelines for clinicians entering into interview-based research in the qualitative research literature. In the absence of formal guidelines, we suggest the use of reflexivity throughout the interview process as a means to become more accomplished in this area. We present our own experiences as a novice general practitioner (GP) researcher undertaking a PhD study and her experienced supervisors. The PhD study used critical phenomenology through in-depth interviews to understand the experience of the patient-doctor relationship between same-sex attracted women and their usual GP in Australia.</p> <p>Results</p> <p>We used reflexivity to improve the rigour of the data collection. This enabled improved probing, fewer assumptions, avoidance of premature interpretation, and an accentuated sense of curiosity during interviews. We also enlisted reciprocity between interviewer and interviewee as a tool to improve engagement and trust, share interview control, and ultimately improve the depth of the interview content.</p> <p>Conclusion</p> <p>Preparatory recommendations for novice clinician research interviewers include the importance of recognising the multiple identities that they bring to the interview. In this setting in particular this involves acknowledging the clinician interviewer as a potential insider in relation to interviewees and negotiating shared understanding to avoid insider assumptions. Other essential requirements are having an experienced research supervisor, arranging pilot interviews that include active feedback on interviewing style from interviewees, and being reflexive during interviews. More formal guidelines for in-depth interviewing skills development are needed.</p

Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies

<p>Abstract</p> <p>Background</p> <p>Until recently, genome-wide association studies (GWAS) have been restricted to research groups with the budget necessary to genotype hundreds, if not thousands, of samples. Replacing individual genotyping with genotyping of DNA pools in Phase I of a GWAS has proven successful, and dramatically altered the financial feasibility of this approach. When conducting a pool-based GWAS, how well SNP allele frequency is estimated from a DNA pool will influence a study's power to detect associations. Here we address how to control the variance in allele frequency estimation when DNAs are pooled, and how to plan and conduct the most efficient well-powered pool-based GWAS.</p> <p>Methods</p> <p>By examining the variation in allele frequency estimation on SNP arrays between and within DNA pools we determine how array variance [var(e_array)] and pool-construction variance [var(e_construction)] contribute to the total variance of allele frequency estimation. This information is useful in deciding whether replicate arrays or replicate pools are most useful in reducing variance. Our analysis is based on 27 DNA pools ranging in size from 74 to 446 individual samples, genotyped on a collective total of 128 Illumina beadarrays: 24 1M-Single, 32 1M-Duo, and 72 660-Quad.</p> <p>Results</p> <p>For all three Illumina SNP array types our estimates of var(e_array) were similar, between 3-4 × 10^-4for normalized data. Var(e_construction) accounted for between 20-40% of pooling variance across 27 pools in normalized data.</p> <p>Conclusions</p> <p>We conclude that relative to var(e_array), var(e_construction) is of less importance in reducing the variance in allele frequency estimation from DNA pools; however, our data suggests that on average it may be more important than previously thought. We have prepared a simple online tool, PoolingPlanner (available at <url>http://www.kchew.ca/PoolingPlanner/</url>), which calculates the effective sample size (ESS) of a DNA pool given a range of replicate array values. ESS can be used in a power calculator to perform pool-adjusted calculations. This allows one to quickly calculate the loss of power associated with a pooling experiment to make an informed decision on whether a pool-based GWAS is worth pursuing.</p

Implementation of multimodal computed tomography in a telestroke network : five-year experience

Aims: Penumbral selection is best-evidence practice for thrombectomy in the 6-24 hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal computed tomography (mCT) at the primary centre—including noncontrast CT, CT perfusion, and CT angiography—may enhance reperfusion therapy decision-making. We developed a network with five spoke primary stroke sites and assessed safety, feasibility, and influence of mCT in rural hospitals on decision-making for thrombolysis. Methods: Consecutive patients assessed via telemedicine from April 2013 to June 2018. Clinical outcomes were measured, and decision-making compared using theoretical models for reperfusion therapy applied without mCT guidance. Symptomatic intracranial hemorrhage (sICH) was assessed according to Safe Implementation of Treatments in Stroke Thrombolysis Registry criteria. Results: A total of 334 patients were assessed, 240 received mCT, 58 were thrombolysed (24.2%). The mean age of thrombolysed patients was 70 years, median baseline National Institutes of Health Stroke Scale was 10 (IQR 7-18) and 23 (39.7%) had a large vessel occlusion. 1.7% had sICH and 3.5% parenchymal hematoma. Three months poststroke, 55% were independent, compared with 70% in the non-thrombolysed group. Conclusion: Implementation of CTP in rural centers was feasible and led to high thrombolysis rates with low rates of sICH. © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd