Outcomes for Degenerative Cervical Myelopathy Following Implementation of the AO Spine International Guidelines: A Single-Centre Service Evaluation.

Introduction: Degenerative cervical myelopathy (DCM) is a syndrome of symptomatic cervical spinal cord compression due to degenerative spinal changes. Until recently there was no formal consensus on exactly which patients are suitable for surgical or conservative management. The AO Spine international guidelines were introduced to address this issue, based on the best available current evidence.

Interventions to optimise preoperative fasting in paediatrics: a scoping review.

Background: Preoperative fasting is the standard of care for patients undergoing a procedure under general anaesthesia. Despite the increased leniency of fasting guideline recommendations, prolonged preoperative fasting periods continue to disproportionally affect paediatric patients. This review maps existing interventions optimising paediatric fasting practices, to explore strategies that can be best applied in clinical practice.

Seniority of Surgeon in Chronic Subdural Hematoma Recurrence: A Systematic Review and Meta-analysis.

Chronic subdural hematoma (CSDH) is increasingly common, particularly in the older and multimorbid population. Surgical proficiency in management is required in the early years of U.K.

Impact of antithrombotic agents on outcomes in patients requiring surgery for chronic subdural haematoma: a systematic review and meta-analysis.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events.

Superior cortical venous anatomy for endovascular device implantation: a systematic review.

Endovascular electrode arrays provide a minimally invasive approach to access intracranial structures for neural recording and stimulation. These arrays are currently used as brain-computer interfaces (BCIs) and are deployed within the superior sagittal sinus (SSS), although cortical vein implantation could improve the quality and quantity of recorded signals. However, the anatomy of the superior cortical veins is heterogenous and poorly characterised.

Management of mild degenerative cervical myelopathy and asymptomatic spinal cord compression: an international survey.

Study Design: Cross-sectional survey.

Objective: Currently there is limited evidence and guidance on the management of mild degenerative cervical myelopathy (DCM) and asymptomatic spinal cord compression (ASCC). Anecdotal evidence suggest variance in clinical practice.

Endovascular Brain-Computer Interfaces in Poststroke Paralysis.

Stroke is a leading cause of paralysis, most frequently affecting the upper limbs and vocal folds. Despite recent advances in care, stroke recovery invariably reaches a plateau, after which there are permanent neurological impairments. Implantable brain-computer interface devices offer the potential to bypass permanent neurological lesions.

A single centre service evaluation of degenerative cervical and thoracic myelopathy.

Background: Degenerative cervical myelopathy (DCM) and degenerative thoracic myelopathy (DTM) present with leg, bladder and bowel symptoms. If imaging confirms spinal cord compression both conditions are usually managed surgically. Surgical timing is important in patient management as it affects post-operative recovery and long-term outcomes.

Secondary analysis of a James Lind Alliance priority setting partnership to facilitate knowledge translation in degenerative cervical myelopathy (DCM): insights from AO Spine RECODE-DCM.

Objectives: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM).

Design: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM.

Participants And Setting: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally.

Osteopathy in the Early Diagnosis and Management of Degenerative Cervical Myelopathy: National Survey.

Background: Degenerative cervical myelopathy (DCM) is a common and disabling neurodegenerative condition. Surgical decompression is the only evidence-based treatment to halt disease progression; however, diagnosis and access to timely treatment are often delayed, which contribute to significant disability and dependence. Supporting early diagnosis and access to timely treatment is a critical priority.

Personalised therapeutic approaches to glioblastoma: A systematic review.

Introduction: Glioblastoma is the most common and malignant primary brain tumour with median survival of 14.6 months. Personalised medicine aims to improve survival by targeting individualised patient characteristics.

Degenerative cervical myelopathy education in UK medical schools: a national cross-sectional survey of medical students.

Introduction: Degenerative cervical myelopathy (DCM) is a common and progressive neurological condition caused by injury of the cervical spinal cord by degenerative spinal pathology. Delayed diagnosis leading to avoidable and irreversible disability is a major current problem limiting patient outcomes. Lack of sufficient representation of DCM in undergraduate and postgraduate medical curricula may contribute to poor recognition of DCM by non-specialist doctors.

Hard collar immobilisation following elective surgery on the cervical spine: a cross-sectional survey of UK spinal surgeons.

Introduction: Although mostly used in the management of spinal trauma, hard collar immobilisation is also used as an adjunct to recovery after elective cervical spine surgery. Many surgeons believe that bracing reduces the risk of non-union and pain and provides a subjective sense of security for patients. There is little if any, evidence for this practice and immobilisation can be a direct cause of adverse events.

Drug discovery in leishmaniasis using protein lipidation as a target.

The leishmaniases are infectious diseases caused by a number of species of obligate intracellular protozoa of the genus with disease manifesting as cutaneous, mucocutaneous and visceral forms. Despite being endemic in more than 80 countries and its being the cause of high morbidity and mortality, leishmaniasis remains a neglected tropical disease. Chemotherapy is the frontline treatment, but drugs in current use suffer from toxic side effects, difficulties in administration and extended treatment times - moreover, resistance is emerging.

The forgotten drought of 1765-1768: Reconstructing and re-evaluating historical droughts in the British and Irish Isles.

Historical precipitation records are fundamental for the management of water resources, yet rainfall observations typically span 100-150 years at most, with considerable uncertainties surrounding earlier records. Here, we analyse some of the longest available precipitation records globally, for England and Wales, Scotland and Ireland. To assess the credibility of these records and extend them further back in time, we statistically reconstruct (using independent predictors) monthly precipitation series representing these regions for the period 1748-2000.

Novel Thienopyrimidine Inhibitors of -Myristoyltransferase with On-Target Activity in Intracellular Amastigotes.

The leishmaniases, caused by species of protozoan parasites, are neglected tropical diseases with millions of cases worldwide. Current therapeutic approaches are limited by toxicity, resistance, and cost. -Myristoyltransferase (NMT), an enzyme ubiquitous and essential in all eukaryotes, has been validated via genetic and pharmacological methods as a promising anti-leishmanial target.

Crystal structures of the GH18 domain of the bifunctional peroxiredoxin-chitinase CotE from Clostridium difficile.

CotE is a coat protein that is present in the spores of Clostridium difficile, an obligate anaerobic bacterium and a pathogen that is a leading cause of antibiotic-associated diarrhoea in hospital patients. Spores serve as the agents of disease transmission, and CotE has been implicated in their attachment to the gut epithelium and subsequent colonization of the host. CotE consists of an N-terminal peroxiredoxin domain and a C-terminal chitinase domain.

Water Networks Can Determine the Affinity of Ligand Binding to Proteins.

Solvent organization is a key but underexploited contributor to the thermodynamics of protein-ligand recognition, with implications for ligand discovery, drug resistance, and protein engineering. Here, we explore the contribution of solvent to ligand binding in the virulence protein SiaP. By introducing a single mutation without direct ligand contacts, we observed a >1000-fold change in sialic acid binding affinity.

Site-selective C-C modification of proteins at neutral pH using organocatalyst-mediated cross aldol ligations.

The bioconjugation of proteins with small molecules has proved an invaluable strategy for probing and perturbing biological mechanisms. The general use of chemical methods for protein functionalisation can be limited however by the requirement for complicated reaction partners to be present in large excess, and harsh conditions which are incompatible with many protein scaffolds. Herein we describe a site-selective organocatalyst-mediated protein aldol ligation (OPAL) that affords stable carbon-carbon linked bioconjugates at neutral pH.

Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus.

Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry.

Structure-guided optimization of quinoline inhibitors of -myristoyltransferase.

The parasite is the most widely distributed cause of recurring malaria. -Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both and -myristoyltransferase (NMT).