Epidural corticosteroid injections for lumbosacral radicular pain.

Background: Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space, with the aim of reducing the local inflammatory process and, consequently, relieving the symptoms of lumbosacral radicular pain. This Cochrane Review is an update of a review published in Annals of Internal Medicine in 2012.

Modeling cancer genomic data in yeast reveals selection against ATM function during tumorigenesis.

The DNA damage response (DDR) comprises multiple functions that collectively preserve genomic integrity and suppress tumorigenesis. The Mre11 complex and ATM govern a major axis of the DDR and several lines of evidence implicate that axis in tumor suppression. Components of the Mre11 complex are mutated in approximately five percent of human cancers.

Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures.

The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics.

Socio-demographic and ecological factors associated with anti-HCV prevalence in people who inject drugs: A systematic review.

Background: The World Health Organization (WHO) aim to eliminate hepatitis C virus (HCV) as a public health threat by 2030. People who inject drugs (PWID) are a key risk group for HCV transmission globally. We explored socio-demographic and ecological variables associated with HCV antibody (anti-HCV) prevalence among samples of PWID.

Protein and Antibody Delivery into Difficult-to-Transfect Cells by Polymeric Peptide Mimics.

Intracellular protein delivery using simple noncovalent carriers is an emerging field advancing the study of intracellular pathways and novel therapeutics. Here, we directly compare green fluorescent protein delivery using our recently reported protein transduction domain mimic (PTDM) to delivery with four commercially available amphiphilic macromolecular carriers in five diverse cell types. While most carriers succeeded only in serum-free conditions, the PTDM maintained robust delivery in complete media, even when tasked with antibody delivery into difficult-to-transfect neurons for the first time.

Cost and Outcomes of Implantable Cardiac Electronic Device Infections in Victoria, Australia.

Background: Implantable cardiac electronic device (ICED) infections are associated with significant morbidity, mortality and cost. The aim of this study was to perform the first analysis for the cost of ICED infection in Australia. Secondary aims were to provide an update on the incidence, burden and outcomes of ICED infections and an analysis of the hospital ICD-10 codes used for ICED infection admissions.

Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis.

Background: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.

Methods: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018.

Reductions in emergency department presentations associated with opioid agonist treatment vary by geographic location: A retrospective study in New South Wales, Australia.

Introduction And Aims: It is not known if the reduction in ED use during periods of OAT occurs across urgent and low acuity presentations. We aimed to compare the incidence and costs of urgent and low acuity ED presentations of people with opioid use disorder (OUD) in and out of opioid agonist treatment (OAT).

Design And Methods: This was a retrospective cohort study (N=24,875), using linked administrative health data from New South Wales (NSW), Australia.

(New) Methods for Detection of Resistance in Clinical Samples.

Purpose Of Review: The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of with increasing resistance observed against triazole antifungals, including voriconazole and isavuconazole, the most commonly used antifungal agents for the disease. Culture-based methods for determining triazole resistance are still the gold standard but are time consuming and lack sensitivity. We sought to provide an update on non-culture-based methods for detecting resistance patterns to .

Conformational State Hopping of Knots in Tensioned Polymer Chains.

We use Brownian dynamics simulations to study the conformational states of knots on tensioned chains. Focusing specifically on the 8 knot, we observe knot conformational state hopping and show that the process can be described by a two-state kinetic model in the presence of an external force. The distribution of knot conformational states depends on the applied chain tension, which leads to a force-dependent distribution of knot untying pathways.

Modelling the potential prevention benefits of a treat-all hepatitis C treatment strategy at global, regional and country levels: A modelling study.

The World Health Organization (WHO) recently produced guidelines advising a treat-all policy for HCV to encourage widespread treatment scale-up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country-level factors affect impact.

How to Untie a Protein Knot.

The origin of protein backbone threading through a topological knot remains elusive. To understand the evolutionary origin of protein knots, in this issue of StructureKo et al. (2019) used circular permutation to untie a knotted protein.

Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies.

Proteins associated with familial neurodegenerative disease often aggregate in patients' neurons. Several such proteins, e.g.

Take-Home Naloxone for the Emergency Interim Management of Opioid Overdose: The Public Health Application of an Emergency Medicine.

Naloxone is a well-established essential medicine for the treatment of life-threatening heroin/opioid overdose in emergency medicine. Over two decades, the concept of 'take-home naloxone' has evolved, comprising pre-provision of an emergency supply to laypersons likely to witness an opioid overdose (e.g.

Mechanical Unfolding and Folding of a Complex Slipknot Protein Probed by Using Optical Tweezers.

Knotted and slipknotted proteins are topologically complex. Understanding their folding and unfolding mechanism has attracted considerable interest. Here we combined protein engineering, single-molecule optical tweezers, and steered molecular dynamics (SMD) simulations to investigate the mechanical unfolding and folding of a slipknotted protein pyruvoyl-dependent arginine decarboxylase (PADC).

Three-dimensional culture of endometrial cells from domestic cats: A new in vitro platform for assessing plastic toxicity.

Plastic polymers can be combined with additives that modify physical properties and stability of the material. However, the biocompatibility of those additives is not well known. The objective of the study was to characterize the impact of zinc stearate-a common additive-through the development of a novel three-dimensional (3-D) in vitro platform with endometrial cells from domestic cats.

Deep Learning With Asymmetric Connections and Hebbian Updates.

We show that deep networks can be trained using Hebbian updates yielding similar performance to ordinary back-propagation on challenging image datasets. To overcome the unrealistic symmetry in connections between layers, implicit in back-propagation, the feedback weights are separate from the feedforward weights. The feedback weights are also updated with a local rule, the same as the feedforward weights-a weight is updated solely based on the product of activity of the units it connects.

Association of Cohort and Individual Substance Use With Risk of Transitioning to Drug Use, Drug Use Disorder, and Remission From Disorder: Findings From the World Mental Health Surveys.

Importance: Limited empirical research has examined the extent to which cohort-level prevalence of substance use is associated with the onset of drug use and transitioning into greater involvement with drug use.

Objective: To use cross-national data to examine time-space variation in cohort-level drug use to assess its associations with onset and transitions across stages of drug use, abuse, dependence, and remission.

Design, Setting, And Participants: The World Health Organization World Mental Health Surveys carried out cross-sectional general population surveys in 25 countries using a consistent research protocol and assessment instrument.

Cross-national patterns of substance use disorder treatment and associations with mental disorder comorbidity in the WHO World Mental Health Surveys.

Aims: To examine cross-national patterns of 12-month substance use disorder (SUD) treatment and minimally adequate treatment (MAT), and associations with mental disorder comorbidity.

Design: Cross-sectional, representative household surveys.

Setting: Twenty-seven surveys from 25 countries of the WHO World Mental Health Survey Initiative.

Direct observation of the fast and robust folding of a slipknotted protein by optical tweezers.

Understanding the folding mechanism of knotted and slipknotted proteins has attracted considerable interest. Due to their topological complexity, knotted and slipknotted proteins are predicted to fold slowly and involve large topological barriers. Molecular dynamics simulation studies suggest that a slipknotted conformation can serve as an important intermediate to help greatly reduce the topological difficulty during the folding of some knotted proteins.

Untying a Protein Knot by Circular Permutation.

Topologically knotted proteins are tantalizing examples of how polypeptide chains can explore complex free energy landscapes to efficiently attain defined knotted conformations. The evolution trails of protein knots, however, remain elusive. We used circular permutation to change an evolutionally conserved topologically knotted SPOUT RNA methyltransferase into an unknotted form.