Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial.

Background: Acute demyelinating optic neuritis, a common feature of multiple sclerosis, can damage vision through neurodegeneration in the optic nerve and in its fibres in the retina. Inhibition of voltage-gated sodium channels is neuroprotective in preclinical models. In this study we aimed to establish whether sodium-channel inhibition with phenytoin is neuroprotective in patient with acute optic neuritis.

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

Introduction: Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak.

Systemic Chemotherapeutic Agents as Adjunctive Periodontal Therapy: A Narrative Review and Suggested Clinical Recommendations.

Periodontitis is an inflammatory condition of the periodontium that leads to destruction of the supporting structures of the tooth, including loss of attachment and alveolar bone. A clinician's first line of treatment for periodontitis is traditionally mechanical periodontal therapy, including oral hygiene instructions together with scaling and root planing. How- ever, it has been shown that mechanical therapy may not always be effective in halting disease.

A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation.

Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop.

Effects of Transcription Elongation Rate and Xrn2 Exonuclease Activity on RNA Polymerase II Termination Suggest Widespread Kinetic Competition.

The torpedo model of transcription termination asserts that the exonuclease Xrn2 attacks the 5'PO4-end exposed by nascent RNA cleavage and chases down the RNA polymerase. We tested this mechanism using a dominant-negative human Xrn2 mutant and found that it delayed termination genome-wide. Xrn2 nuclease inactivation caused strong termination defects downstream of most poly(A) sites and modest delays at some histone and U snRNA genes, suggesting that the torpedo mechanism is not limited to poly(A) site-dependent termination.

Is Real-Time Feedback of Burn-Specific Patient-Reported Outcome Measures in Clinical Settings Practical and Useful? A Pilot Study Implementing the Young Adult Burn Outcome Questionnaire.

Long-term follow-up care of survivors after burn injuries can potentially be improved by the application of patient-reported outcome measures (PROMs). PROMs can inform clinical decision-making and foster communication between the patient and provider. There are no previous reports using real-time, burn-specific PROMs in clinical practice to track and benchmark burn recovery over time.

Measures of Total Energy Expenditure and Its Components Using the Doubly Labeled Water Method in Rehabilitating Burn Children.

Background: A persistent hypermetabolic state delays anabolism and growth in burned children. However, our own clinical experience has been that resting energy expenditure (REE) is not increased during the rehabilitative phase, suggesting other contributing factors. We measured total energy expenditure (TEE) and its components in rehabilitating pediatric burn patients to identify the basis for accelerated energy metabolism in this population.

TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis.

Unraveling the Role of Alkyl F on CH-π Interactions and Uncovering the Tipping Point for Fluorophobicity.

Although fluorine often plays an influential role in molecular recognition, little is known about the effect of aliphatic fluorine on the CH-π interaction in solution. A series of molecular balances were synthesized that contain fluorinated and nonfluorinated alkyl groups. Our findings indicate that fluorine's polarizing ability does enhance CH-π binding and depends on molecular orientation.

Increased frequency of double and triple heterozygous gene variants in children with intrahepatic cholestasis.

Aim: Single gene mutations cause syndromes of intrahepatic cholestasis, but previous multi-gene mutation screening in children with idiopathic cholestasis failed to fulfill diagnostic criteria in approximately two-thirds of children. In adults with fibrosing cholestatic disease, heterozygous ABCB4 mutations were present in 34% of patients. Here, we hypothesized that children with idiopathic cholestasis have a higher frequency of heterozygous non-synonymous gene sequence variants.

A Prognosis System for Periimplant Diseases.

Introduction: Periimplant diseases have slowly become a common complication in implant patients. Here, we present a prognosis system to aid clinicians and researchers in the evaluation and treatment of periimplant diseases. This prognosis system divides periimplant disease into favorable, questionable, unfavorable, and hopeless cases based on the level of bone loss, pocket depth, mobility, bleeding on probing, and suppuration.

The Relative Importance of Domain Applicability Metrics for Estimating Prediction Errors in QSAR Varies with Training Set Diversity.

Unlabelled: In QSAR, a statistical model is generated from a training set of molecules (represented by chemical descriptors) and their biological activities (an "activity model"). The aim of the field of domain applicability (DA) is to estimate the uncertainty of prediction of a specific molecule on a specific activity model. A number of DA metrics have been proposed in the literature for this purpose.

Deep neural nets as a method for quantitative structure-activity relationships.

Neural networks were widely used for quantitative structure-activity relationships (QSAR) in the 1990s. Because of various practical issues (e.g.

An overview of clinical associate roles in the neurointerventional specialty.

Neurointerventionalists have long partnered with certain types of clinical associates to provide longitudinal care. This overview summarizes differences in education, background, roles, and scopes of practice of the various clinical associates (physician assistants, nurse practitioners, clinical nurse specialists, radiology practitioner assistants, radiologist assistants, and nursing care coordinators). Key differences and similarities are highlighted to alleviate confusion about the roles clinical associates can assume on a neurointerventional service.

Nutrition and metabolism in the rehabilitative phase of recovery in burn children: a review of clinical and research findings in a speciality pediatric burn hospital.

During the rehabilitation phase of burn injury, patient care transitions from critical care medicine to restorative treatment strategies that encompass physical and occupational therapies, nutrition repletion, and psychosocial support for community reintegration. As pediatric burn patients undergo rehabilitation, nutrition assessment remains ongoing to define nutritional status and any alterations in metabolism that may take place. For some, a persistent hypermetabolic state appears evident, and weight loss may continue.

eCounterscreening: using QSAR predictions to prioritize testing for off-target activities and setting the balance between benefit and risk.

During drug development, compounds are tested against counterscreens, a panel of off-target activities that would be undesirable for a drug to have. Testing every compound against every counterscreen is generally too costly in terms of time and money, and we need to find a rational way of prioritizing counterscreen testing. Here we present the eCounterscreening paradigm, wherein predictions from QSAR models for counterscreen activity are used to generate a recommendation as to whether a specific compound in a specific project should be tested against a specific counterscreen.

Recovery trajectories after burn injury in young adults: does burn size matter?

The impact of burn size on mortality is well known, but the association of burn size with the trajectories of long-term functional outcomes remains poorly studied. This prospective multi-center study included burned adults ages 19 to 30 years who completed the Young Adult Burn Outcome Questionnaire at initial baseline contact, 2 weeks, and at 6 and 12 months after initial questionnaire administration. Non-burned adults of comparable ages also completed the questionnaire as a reference group.

Discrepancy in Initial Pediatric Burn Estimates and Its Impact on Fluid Resuscitation.

One of the fundamental aspects of initial burn care is the ability to accurately measure the TBSA of injured tissue. Discrepancies between initial estimates of burn size and actual TBSA (determined at the burn unit) have long been reported. These inconsistencies have the potential for unnecessary patient transfer and inappropriate fluid administration which may result in morbidity.

An automated image processing method to quantify collagen fibre organization within cutaneous scar tissue.

Standard approaches to evaluate scar formation within histological sections rely on qualitative evaluations and scoring, which limits our understanding of the remodelling process. We have recently developed an image analysis technique for the rapid quantification of fibre alignment at each pixel location. The goal of this study was to evaluate its application for quantitatively mapping scar formation in histological sections of cutaneous burns.

Inpatient rehabilitation experience of children with burn injuries: a 10-yr review of the uniform data system for medical rehabilitation.

Objective: This study aimed to describe the pediatric burn inpatient rehabilitation population and short-term functional outcomes using the Uniform Data System for Medical Rehabilitation.

Design: This is a secondary analysis of data from the Uniform Data System for Medical Rehabilitation database between 2002 and 2011 included children younger than 18 yrs at time of admission to inpatient rehabilitation with primary diagnosis of burn injury. Demographic, medical, and functional data were evaluated.