Nerve root block versus surgery (NERVES) for the treatment of radicular pain secondary to a prolapsed intervertebral disc herniation: study protocol for a multi-centre randomised controlled trial.

Background: Sciatica is a common condition reported to affect over 3% of the UK population at any time and is often caused by a prolapsed intervertebral disc (PID). Although the duration and severity of symptoms can vary, pain persisting beyond 6 weeks is unlikely to recover spontaneously and may require investigation and treatment. Currently, there is no specific care pathway for sciatica in the National Health Service (NHS), and no direct comparison exists between surgical microdiscectomy and transforaminal epidural steroid injection (TFESI).

CRL4 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.

Multi-subunit cullin-RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation.

Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review.

Background: Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment up to 70% of individuals with active epilepsy have the potential to become seizure-free, and to go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, sodium valproate and phenytoin are commonly used antiepileptic drugs for monotherapy treatment.

Rare coding variants in genes encoding GABA receptors in genetic generalised epilepsies: an exome-based case-control study.

Background: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes using recombinant viral vectors, which do not target transgenes to specific genomic sites. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair.

Revisiting IL-2: Biology and therapeutic prospects.

Interleukin-2 (IL-2), the first cytokine that was molecularly cloned, was shown to be a T cell growth factor essential for the proliferation of T cells and the generation of effector and memory cells. On the basis of this activity, the earliest therapeutic application of IL-2 was to boost immune responses in cancer patients. Therefore, it was a surprise that genetic deletion of the cytokine or its receptor led not only to the expected immune deficiency but also to systemic autoimmunity and lymphoproliferation.

Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review.

Background: This is an updated version of the original Cochrane Review published in Issue 11, 2006 of the Cochrane Database of Systematic Reviews.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment up to 70% of individuals with active epilepsy have the potential to become seizure-free, and to go into long-term remission shortly after starting drug therapy with a single antiepileptic drug (AED) in monotherapy.

Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation.

In this Letter, analysis of steady-state regulatory T (Treg) cell percentages from Il2ra enhancer deletion (EDEL) and wild-type (WT) mice revealed no differences between them (Extended Data Fig. 9d). This analysis included two mice whose genotypes were incorrectly assigned.

Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms.

Site-specific eukaryotic genome editing with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems has quickly become a commonplace amongst researchers pursuing a wide variety of biological questions. Users most often employ the Cas9 protein derived from Streptococcus pyogenes in a complex with an easily reprogrammed guide RNA (gRNA). These components are introduced into cells, and through a base pairing with a complementary region of the double-stranded DNA (dsDNA) genome, the enzyme cleaves both strands to generate a double-strand break (DSB).

Antiepileptic drugs as prophylaxis for postcraniotomy seizures.

Background: This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery.

Rufinamide add-on therapy for refractory epilepsy.

Background: Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical activity in the brain. Despite the development of more than 10 new antiepileptic drugs (AEDs) since the early 2000s, approximately a third of people with epilepsy remain resistant to pharmacotherapy, often requiring treatment with a combination of AEDs.

The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service.

There is an increasing interest in the use of the ketogenic diet (KD) as an adjuvant therapy for glioma patients. We assessed the tolerability and feasibility of a modified ketogenic diet (MKD) in patients with glioma, along with willingness of patients to participate in future randomized controlled trials. The study was undertaken in two parts; a patient questionnaire and evaluation of the diet.

The role of ketogenic diets in the therapeutic management of adult and paediatric gliomas: a systematic review.

Aim: We performed a systematic review of the evidence for effectiveness and acceptability of different ketogenic diets (KDs) in the therapeutic management of gliomas.

Methods: The search strategy included searches of seven electronic databases. Data extraction and quality assessment were undertaken independently by two authors.

A voxel-based asymmetry study of the relationship between hemispheric asymmetry and language dominance in Wada tested patients.

Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole-brain voxel-based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients.

The prescribable drugs with efficacy in experimental epilepsies (PDE3) database for drug repurposing research in epilepsy.

Objective: Current antiepileptic drugs (AEDs) have several shortcomings. For example, they fail to control seizures in 30% of patients. Hence, there is a need to identify new AEDs.

Genetic variation in predicts phenytoin-induced maculopapular exanthema in European-descent patients.

Objective: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs.

Methods: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed.

Epilepsy and psychosis: a practical approach.

The psychoses of epilepsy can be classified according to their temporal relationship with seizures, namely as ictal, postictal and interictal psychosis. Interictal psychosis is the most common and may resemble schizophrenia. They can be challenging to diagnose and to manage, especially given the perception that some antipsychotic drugs may exacerbate seizures, while some antiepileptic medications may worsen psychosis.

A critical review of recent clinical practice guidelines on management of cryptorchidism.

Background/purpose: Limited efforts have been made in assessing the qualities of clinical practice guidelines (CPGs) on cryptorchidism (UDT). This appraisal aims to determine the quality of recent CPGs on the management of UDT.

Methods: After systematic literature search, all English-based CPGs providing recommendations for the management of UDT from 2012 to 2017 were reviewed.

Breakthrough seizures-Further analysis of the Standard versus New Antiepileptic Drugs (SANAD) study.

Objectives: To develop prognostic models for risk of a breakthrough seizure, risk of seizure recurrence after a breakthrough seizure, and likelihood of achieving 12-month remission following a breakthrough seizure. A breakthrough seizure is one that occurs following at least 12 months remission whilst on treatment.

Methods: We analysed data from the SANAD study.

Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

Background: Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.

Multiplexed droplet single-cell RNA-sequencing using natural genetic variation.

Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that harnesses natural genetic variation to determine the sample identity of each droplet containing a single cell (singlet) and detect droplets containing two cells (doublets).

Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial): study protocol for a randomised pilot study.

Background: Glioblastoma is the commonest form of malignant brain tumour in adults, affecting 2-3 people per 100,000 per year. Despite current treatment options including surgical resection, radiotherapy and temozolomide chemotherapy, overall survival at 2 years is approximately 27%, with a median survival of 12-14 months. The ketogenic diet (KD) is postulated to work by simulating the metabolic response to fasting by promoting the utilisation of ketones as a primary energy source, and depriving the glycolytic pathways utilised by malignant glioma cells for growth.

Preoperative progressive pneumoperitoneum in obese patients with loss of domain hernias.

Background: Repair of hernias with loss of domain in obese patients can lead to acute respiratory failure.

Objectives: The objective of this study was to analyze preoperative progressive pneumoperitoneum (PPP) in increasing abdominal cavity volume and its impact on respiratory function.

Setting: The study was conducted at the University Hospital, State University of Londrina, Brazil, which is a referral center for the treatment of obesity.