Two Decades of Publishing Excellence in Pharmaceutical Biotechnology

Recombinant biological products have revolutionized modern medicine by providing both remarkably effective vaccines to prevent disease and therapeutic drugs to treat a wide variety of unmet medical needs. Since the early 1980s, dozens of new therapeutic protein drugs and macromolecular vaccines have been commercialized, which have benefitted millions of patients worldwide. The pharmaceutical development of these biological products presented many scientific and technical challenges, some of which continue today with newer candidates including recombinant protein-based vaccines with novel adjuvants, peptide and RNA-based drugs, and stem cellular therapies. Compared with small molecule drugs, the characterization, stabilization, formulation, and delivery of biomolecules share common hurdles as well as unique challenges. This area of drug development research has been referred to as “pharmaceutical biotechnology”, in recognition of the critical role that recombinant DNA technology plays in the design and production of most of these biological products. Current research focus areas in this field include (i) determination of structural integrity of the primary sequence, post-translational modifications, and higher-order three dimensional shapes, (ii) assessment of physicochemical degradation pathways and their effects on biological activity and potency, (iii) formulation design and development to optimize stability and delivery, (iv) evaluating and optimizing process development steps including lyophilization and fill-finish, (v) analytical method development and applications of new instruments and data visualization tools, (vi) design and development of drug delivery approaches, and (vii) studies of biological effects including pharmacokinetics, pharmacodynamics, and adverse immunogenicity. During the early days of pharmaceutical biotechnology research, there were numerous scientific challenges because the analytical characterization approaches needed for development of recombinant biological molecules in “real world” pharmaceutical dosage forms were essentially unknown. Furthermore, understanding critical drug product manufacturing issues (e.g., stability of biological compounds during processing, storage, and shipping as well as reproducibility of fill-finish production technologies) and behavior during and after patient administration was often achieved by “on-the-job” training. Fortunately, the pioneers in the field regularly presented research at key conferences and started publishing early in pharmaceutical sciences journals such as Journal of Pharmaceutical Sciences. Recognizing this critically important new field, the then Editor of the journal, Professor Bill Higuchi, instituted a new “pharmaceutical biotechnology” category for research papers. This insightful move was coupled with an equally wise decision to recruit Dr. C. Russell Middaugh as the new Associate Editor for the new research category. As will be detailed below, under Dr. Middaugh’s diligent and expert guidance, pharmaceutical biotechnology papers have grown in number, scope, and impact over the past 20 years, and these days, the Journal of Pharmaceutical Sciences is viewed by scientific leaders in the field as the “go to” place for publication of the most important results and descriptions of innovations in pharmaceutical biotechnology

Detecting microRNA activity from gene expression data

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions.</p> <p>Results</p> <p>Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance.</p> <p>Conclusions</p> <p>We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.</p

Development of a new diabetes medication self-efficacy scale and its association with both reported problems in using diabetes medications and self-reported adherence

Background: Although there are several different general diabetes self-efficacy scales, there is a need to develop a self-efficacy scale that providers can use to assess patient’s self-efficacy regarding medication use. The purpose of this study was to: 1) develop a new diabetes medication self-efficacy scale and 2) examine how diabetes medication self-efficacy is associated with patient-reported problems in using diabetes medications and self-reported adherence. Patients and methods: Adult English-speaking patients with type 2 diabetes were recruited from a family medicine clinic and a pharmacy in Eastern North Carolina, USA. The patients were eligible if they reported being nonadherent to their diabetes medicines on a visual analog scale. Multivariable regression was used to examine the relationship between self-efficacy and the number of reported diabetes medication problems and adherence. Results: The diabetes medication self-efficacy scale had strong reliability (Cronbach’s alpha =0.86). Among a sample (N=51) of mostly African-American female patients, diabetes medication problems were common (6.1±3.1) and a greater number of diabetes medications were associated with lower medication adherence (odds ratio: 0.35; 95% confidence interval: 0.13, 0.89). Higher medication self-efficacy was significantly related to medication adherence (odds ratio: 1.17; 95% confidence interval: 1.05, 1.30) and inversely related to the number of self-reported medication problems (β=-0.13; P=0.006). Conclusion: Higher diabetes medication self-efficacy was associated with fewer patient- reported medication problems and better medication adherence. Assessing medication-specific self-efficacy may help to identify medication-related problems that providers can help the patients address, potentially improving adherence and patient outcomes. Keywords: diabetes, adherence, self-efficacy, literac

The effect of conflicting medication information and physician support on medication adherence for chronically ill patients

This article explores the effect of conflicting information, defined as contradictory information about medication topics from different sources, on medication adherence in a sample of chronically ill patients. We specifically investigate whether conflicting information and physician support directly affect medication adherence or whether the effect is mediated by adherence self-efficacy and outcome expectations for medications

Use and Perceived Credibility of Medication Information Sources for Patients with a Rare Illness: Differences by Gender

Patients with rare illnesses may use medication information sources that are appreciably different from those used by patients with more common illnesses. This article's purpose is to describe vasculitis patients' most frequently used medication information sources, determine which sources patients perceive as credible, and explore gender differences in source use and perceived credibility. Using an online questionnaire, patients (n=232) indicated how often they obtained medication information from 12 sources during the previous year and rated the credibility of 6 sources. The authors used multivariate analysis of covariance and follow-up contrasts to test for gender differences in source use and conducted t tests to compare patients' perceived credibility ratings. Patients used physicians and the Internet most often to obtain medication information and rated them as the most credible sources. Male patients used their spouse/partner more often and rated them as more credible than did female patients. Female patients were more likely to use medication package inserts and the Internet and were less likely to use nurses than were male patients. There appear to be similarities and differences between the information-seeking behaviors of vasculitis patients and other patient populations. Because male patients view their spouse/partner as a credible information source, providers may want to involve the spouse/partner in prescription decision making

CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation

Particulate ligands including cholesterol crystals and amyloid fibrils induce NLRP3-dependent production of interleukin-1β (IL-1β) in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands including oxidized-LDL, amyloid-β and amylin peptides accumulate in these diseases. Here we identify a CD36-mediated endocytic pathway that coordinates the intracellular conversion of these soluble ligands to crystals or fibrils, resulting in lysosomal disruption and NLRP3-inflammasome activation. Consequently, macrophages lacking CD36 failed to elicit IL-1β production in response to these ligands and targeting CD36 in atherosclerotic mice reduced serum IL-1β and plaque cholesterol crystal accumulation. Collectively, these findings highlight the importance of CD36 in the accrual and nucleation of NLRP3 ligands from within the macrophage and position CD36 as a central regulator of inflammasome activation in sterile inflammation

Safetxt: a safer sex intervention delivered by mobile phone messaging on sexually transmitted infections (STI) among young people in the UK - protocol for a randomised controlled trial.

INTRODUCTION: Young people aged 16 to 24 have the highest prevalence of genital chlamydia and gonorrhoea compared with other age groups and re-infection rates following treatment are high. Long-term adverse health effects include subfertility and ectopic pregnancy, particularly among those with repeated infections. We developed the safetxt intervention delivered by text message to reduce sexually transmitted infection (STI) by increasing partner notification, condom use and (STI) testing among young people in the UK. METHODS AND ANALYSIS: A single-blind randomised trial to reliably establish the effect of the safetxt intervention on chlamydia and gonorrhoea infection at 1 year. We will recruit 6250 people aged 16 to 24 years who have recently been diagnosed with chlamydia, gonorrhoea or non-specific urethritis from health services in the UK. Participants will be allocated to receive the safetxt intervention (text messages designed to promote safer sexual health behaviours) or to receive the control text messages (monthly messages asking participants about changes in contact details) by an automated remote online randomisation system. The primary outcome will be the cumulative incidence of chlamydia and gonorrhoea infection at 1 year assessed by nucleic acid amplification tests. Secondary outcomes include partner notification, correct treatment of infection, condom use and STI testing prior to sex with new partners. ETHICS AND DISSEMINATION: Ethics approval was obtained from NHS Health Research Authority - London - Riverside Research Ethics Committee (REC reference: 15/LO/1665) and the London School of Hygiene & Tropical Medicine. We will submit the results of the trial for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: International Standard Randomised Controlled Trials Number: ISRCTN64390461. Registered on 17th March 2016. WHO trial registration data set available at: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN64390461. TRIAL PROTOCOL VERSION: 12, 19th July 2018

Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes

Use of Carpenter-Coustan compared to National Diabetes Data Group (NDDG) criteria increases the number of women diagnosed with GDM by 30-50%, but whether treatment of this milder GDM reduces adverse outcomes is unknown. We explored the effects of the diagnostic criteria used on the benefits of GDM treatment

Fostering relations: first sex and marital timings for children raised by kin and non-kin carers

Kinship fostering is generally preferred to non-kin fostering by policy makers in the U.S. and elsewhere. Researchers and policy makers alike tend to provide several proximate reasons for why this may be, generally neglecting an ultimate evolutionary framework. However, kin selection theory predicts that in the absence of genetically related parents, care from kin will result in the most similar life history outcomes. In low-fertility settings, parents typically favour increased investment in embodied capital and thus delayed reproductive life history strategy. Using archival data from the original Kinsey survey, collected in the U.S. from 1938 to 1963, we used survival analyses to compare the effects of living with kin and non-kin fosterers in childhood on timings of first sex and marriage. Our results support a kin selection hypothesis showing that while fostered children have accelerated life histories compared to children from "intact families", kin fosterers buffer children from early sexual and reproductive behaviors, compared to children cared for by non-kin. © 2014 The Authors