Trehalose Glycopolymer Enhances Both Solution Stability and Pharmacokinetics of a Therapeutic Protein.

Biocompatible polymers such as poly(ethylene glycol) (PEG) have been successfully conjugated to therapeutic proteins to enhance their pharmacokinetics. However, many of these polymers, including PEG, only improve the in vivo lifetimes and do not protect proteins against inactivation during storage and transportation. Herein, we report a polymer with trehalose side chains (PolyProtek) that is capable of improving both the external stability and the in vivo plasma half-life of a therapeutic protein.

Prescription of renin-angiotensin system blockers and risk of acute kidney injury: a population-based cohort study.

Objective: To investigate whether there is an association between use of ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) and risk of acute kidney injury (AKI).

Study Design: We conducted a new-user cohort study of the rate of AKI among users of common antihypertensives.

Setting: UK primary care practices contributing to the Clinical Practice Research Datalink (CPRD) eligible for linkage to hospital records data from the Hospital Episode Statistics (HES) database between April 1997 and March 2014.

Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans.

Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed.

Partner Bereavement and Risk of Herpes Zoster: Results from Two Population-Based Case-Control Studies in Denmark and the United Kingdom.

Background: Psychological stress is commonly thought to increase the risk of herpes zoster by causing immunosuppression. However, epidemiological studies on the topic are sparse and inconsistent. We conducted 2 parallel case-control studies of the association between partner bereavement and risk of zoster using electronic healthcare data covering the entire Danish population and general practices in the UK Clinical Practice Research Datalink.

Passive drift or active swimming in marine organisms?

Predictions of organismal movements in a fluid require knowing the fluid's velocity and potential contributions of the organism's behaviour (e.g. swimming or flying).

Dynamics of Hydrogel-Assisted Giant Unilamellar Vesicle Formation from Unsaturated Lipid Systems.

While current research is centered on observing biophysical properties and phenomena in giant unilamellar vesicles (GUVs), little is known about fabrication parameters that control GUV formation. Using different lipids and rehydration buffers, we directly observe varying dynamics of hydrogel-assisted GUV formation via fluorescence microscopy. We observe the effects of buffer ionic strength, osmolarity, agarose density, and pH on the formation of GUVs using neutral and charged lipids.

Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.

Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension.

Compound Property Optimization in Drug Discovery Using Quantitative Surface Sampling Micro Liquid Chromatography with Tandem Mass Spectrometry.

Surface sampling micro liquid chromatography tandem mass spectrometry (SSμLC-MS/MS) was explored as a quantitative tissue distribution technique for probing compound properties in drug discovery. A method was developed for creating standard curves using surrogate tissue sections from blank tissue homogenate spiked with compounds. The resulting standard curves showed good linearity and high sensitivity.

Biomarkers reveal sea turtles remained in oiled areas following the Deepwater Horizon oil spill.

Assessments of large-scale disasters, such as the Deepwater Horizon oil spill, are problematic because while measurements of post-disturbance conditions are common, measurements of pre-disturbance baselines are only rarely available. Without adequate observations of pre-disaster organismal and environmental conditions, it is impossible to assess the impact of such catastrophes on animal populations and ecological communities. Here, we use long-term biological tissue records to provide pre-disaster data for a vulnerable marine organism.

Identifying patients with chronic widespread pain in primary care.

Chronic widespread pain (CWP) is common in the general population. It is unclear how people reporting this problem present in primary care; they may regularly consult for regional pains without being recognized as having a generalized condition. Our objectives were to determine the prevalence of people consulting in primary care for musculoskeletal conditions in different body regions on different occasions (recurrent regional pain consultation), the proportion with diagnosed generalized pain and survey-reported widespread pain, and if they have features characteristic of CWP.

Supporting rabies control in India.

Earlier this year, Tony Fooks and colleagues described how, under a laboratory twinning project run by the World Organisation for Animal Health (OIE), the UK's OIE Reference Laboratory for rabies, based at the APHA in Weybridge, had been working with the Changchun Veterinary Research Institute in the People's Republic of China to help the institute develop into an OIE Reference Laboratory itself (VR, March 5, 2016, vol 178, pp 231-232). Now, the APHA is taking part in a further three-year project to build rabies diagnosis capability in Bangalore, India, as he and his colleagues explain below.

Antiviral Nucleotide Incorporation by Recombinant Human Mitochondrial RNA Polymerase Is Predictive of Increased In Vivo Mitochondrial Toxicity Risk.

Nucleoside or nucleotide inhibitors are a highly successful class of antivirals due to selectivity, potency, broad coverage, and high barrier to resistance. Nucleosides are the backbone of combination treatments for HIV, hepatitis B virus, and, since the FDA approval of sofosbuvir in 2013, also for hepatitis C virus (HCV). However, many promising nucleotide inhibitors have advanced to clinical trials only to be terminated due to unexpected toxicity.

Comparison of the extent and pattern of cognitive impairment among predialysis, dialysis and transplant patients: A cross-sectional study from Australia.

Aim: The aim of this study was to compare the extent of cogntive impairment and the types of cognitive deficits in an Australian cohort of four patient groups with end stage kidney disease. Characteristics predicting the presence of cognitive impairment were also evaluated.

Methods: Observational cross-sectional study of 155 patients with end stage kidney disease are recruited from a regional Australian renal unit.

Detection of intracellular bacteria in exfoliated urothelial cells from women with urge incontinence.

The role of subclinical infection in patients with urge incontinence has been largely ignored. The aim of this study was to test for the presence of intracellular bacteria in exfoliated urothelial cells obtained from the urine of patients with detrusor overactivity or mixed incontinence +/- a history of UTI, and compare this to a control group of patients with stress incontinence and no history of infection. Bacterial cystitis was assessed by routine microbiology and compared to microscopic analysis of urine by Wright staining.

Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States.

A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria.

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/μl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation.

Methodological challenges when carrying out research on CKD and AKI using routine electronic health records.

Research regarding chronic kidney disease (CKD) and acute kidney injury (AKI) using routinely collected data presents particular challenges. The availability, consistency, and quality of renal data in electronic health records has changed over time with developments in policy, practice incentives, clinical knowledge, and associated guideline changes. Epidemiologic research may be affected by patchy data resulting in an unrepresentative sample, selection bias, misclassification, and confounding by factors associated with testing for and recognition of reduced kidney function.

High Rates of Detection of Clade 2.3.4.4 Highly Pathogenic Avian Influenza H5 Viruses in Wild Birds in the Pacific Northwest During the Winter of 2014-15.

In 2014, clade 2.3.4.

Quantification of risk factors for postherpetic neuralgia in herpes zoster patients: A cohort study.

Objective: To investigate risk factors for postherpetic neuralgia, the neuropathic pain that commonly follows herpes zoster.

Methods: Using primary care data from the Clinical Practice Research Datalink, we fitted multivariable logistic regression models to investigate potential risk factors for postherpetic neuralgia (defined as pain ≥90 days after zoster, based on diagnostic or prescription codes), including demographic characteristics, comorbidities, and characteristics of the acute zoster episode. We also assessed whether the effects were modified by antiviral use.

The Functional Activity of the Human Serotonin 5-HT1A Receptor Is Controlled by Lipid Bilayer Composition.

Although the properties of the cell plasma membrane lipid bilayer are broadly understood to affect integral membrane proteins, details of these interactions are poorly understood. This is particularly the case for the large family of G protein-coupled receptors (GPCRs). Here, we examine the lipid dependence of the human serotonin 5-HT1A receptor, a GPCR that is central to neuronal function.

JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue Implicates Myelin Sheath in Intracerebral Dissemination of Infection.

Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection of the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, but it has recently emerged as a drug safety issue through its association with diverse immunomodulatory therapies. To better understand the relationship between the JCV life cycle and PML pathology, we studied autopsy brain tissue from a 70-year-old psoriasis patient on the integrin alpha-L inhibitor efalizumab following a ~2 month clinical course of PML.

Innate and adaptive immune responses to tick-borne flavivirus infection in sheep.

The flaviviruses tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are closely-related genetically and antigenically, have broadly similar host ranges that include rodents and other mammals (including sheep), and are both transmitted by the same tick species, Ixodes ricinus. Although human infection with TBEV results in a febrile illness followed in some cases by encephalitis, humans appear to be much less susceptible to infection with LIV. However, these viruses demonstrate different susceptibilities in sheep; LIV infection causes encephalitic disease, whereas TBEV infection generally does not.

Tissue-Specific Signatures in the Transcriptional Response to Anaplasma phagocytophilum Infection of Ixodes scapularis and Ixodes ricinus Tick Cell Lines.

Anaplasma phagocytophilum are transmitted by Ixodes spp. ticks and have become one of the most common and relevant tick-borne pathogens due to their impact on human and animal health. Recent results have increased our understanding of the molecular interactions between Ixodes scapularis and A.

Diagnosis of acute kidney injury and its association with in-hospital mortality in patients with infective exacerbations of bronchiectasis: cohort study from a UK nationwide database.

Background: Many patients with bronchiectasis have recurrent hospitalisations for infective exacerbations. Acute kidney injury (AKI) is known to be associated with increased in-hospital mortality. This study examined the frequency of AKI, associated risk-factors, and the association of AKI with in-hospital mortality among patients with bronchiectasis.