Engineered Artificial Carboligases Facilitate Regioselective Preparation of Enantioenriched Aldol Adducts.

Controlling regio- and stereoselectivity of aldol additions is generally challenging. Here we show that an artificial aldolase with high specificity for acetone as the aldol donor can be reengineered via single active site mutations to accept linear and cyclic aliphatic ketones with notable efficiency, regioselectivity, and stereocontrol. Biochemical and crystallographic data show how the mutated residues modulate the binding and activation of specific aldol donors, as well as their subsequent reaction with diverse aldehyde acceptors. Broadening the substrate scope of this evolutionarily naïve catalyst proved much easier than previous attempts to redesign natural aldolases, suggesting that such proteins may be excellent starting points for the development of customized biocatalysts for diverse practical applications.

Stereodivergent Evolution of Artificial Enzymes for the Michael Reaction.

Enzymes are valuable biocatalysts for asymmetric synthesis due to their exacting stereocontrol. Changing the selectivity of an existing catalyst for new applications is, however, challenging. Here we show that, in contrast, the stereoselectivity of an artificial enzyme created by design and directed evolution is readily tunable. We engineered a promiscuous artificial retro-aldolase into four stereocomplementary catalysts for the Michael addition of a tertiary carbanion to an unsaturated ketone. Notably, this selectivity is also preserved with alternative Michael nucleophiles. Complete stereodiversification of other designer enzymes should similarly be possible by extension of these approaches.

Chemoselective Henry Condensations Catalyzed by Artificial Carboligases.

The promiscuity of de novo designed enzymes provides a privileged platform for diverse abiological reactions. In this work, we report the first example of a nitroolefin synthase that catalyzes the Henry condensation between aromatic aldehydes and nitromethane. Significant catalytic activity was discovered in the computationally designed and evolved carboligase RA95.5-8, and mutations around the active site were shown to improve the reaction rate, demonstrating the potential to optimize the enzyme by directed evolution. This novel nitroolefin synthase could participate in complex biological cascades, whereby the highly tunable chemoselectivity could afford useful synthetic building blocks.

The costs and characteristics of occupational injuries admitted to a trauma unit.

Occupational injuries requiring admission to a trauma unit were examined to outline the events surrounding the injury and to examine the costs. Sixty-nine patients were admitted over a 12-month period, representing 4.30% of all work-related injuries attending the emergency department and 4.25% of all admissions to the trauma unit. Most were male (91%), working in skilled trade occupations (65%), with a mean age of 38.8 years. Personal protective equipment was used only by 46% of injured workers who should have been using it. Sixty-one percent of patients believed that their injury was preventable. Half of the injuries were to the upper limb, fall was the most frequent mechanism (25%) and the median duration of admission was 2 days. The direct hospital costs were estimated at over 300000 GBP. Failure to use protective equipment and to follow health and safety guidelines suggests that opportunities exist for injury prevention.

Surgical techniques and return to work following carpal tunnel release: a systematic review and meta-analysis.

INTRODUCTION: This systematic review was conducted to evaluate return to work (RTW) following minimally invasive carpal tunnel surgery versus open carpal tunnel release. This study also assesses how RTW as an outcome measure was examined in previous randomized controlled trials (RCTs). METHODS: The bibliographic databases Medline, AMED and CINAHL were systematically searched. We found 15 relevant RCTs. Meta-analysis was possible only for four studies. RESULTS: The result indicates that minimally invasive surgery offers earlier return to work compared to open carpal tunnel release (mean difference -7.2 days; 95% CI -10 to -4.4 days). There were remarkable inconsistencies in how return to work as an outcome measure was examined in different RCTs. CONCLUSIONS: Calculating standardised mean difference in future RCTs would allow future reviews to be more inclusive of the evidence. The authors suggest more consistent approach for evaluating work-related features in future studies. We recommend that new fit note categories introduced by UK Department of Work and Pension (unfit for all work/return to modified work or work adaptations/return to normal work) would be used to identify different levels of return to work.

Improving the accuracy of acetabular cup implantation using a bulls-eye spirit level.

Acetabular introducers have a built-in inclination of 45 degrees to the handle shaft. With patients in the lateral position, surgeons aim to align the introducer shaft vertical to the floor to implant the acetabulum at 45 degrees. We aimed to determine if a bulls-eye spirit level attached to an introducer improved the accuracy of implantation. A small circular bulls-eye spirit level was attached to the handle of an acetabular introducer. A saw bone hemipelvis was fixed to a horizontal, flat surface. A cement substitute was placed in the acetabulum and subjects were asked to implant a polyethylene cup, aiming to obtain an angle of inclination of 45 degrees. Two attempts were made with the spirit level masked and two with it unmasked. The distance of the air bubble from the spirit level's center was recorded by a single assessor. The angle of inclination of the acetabular component was then calculated. Subjects included both orthopedic consultants and trainees. Twenty-five subjects completed the study. Accuracy of acetabular implantation when using the unmasked spirit level improved significantly in all grades of surgeon. With the spirit level masked, 12 out of 50 attempts were accurate at 45 degrees inclination; 11 out of 50 attempts were "open," with greater than 45 degrees of inclination, and 27 were "closed," with less than 45 degrees. With the spirit level visible, all subjects achieved an inclination angle of exactly 45 degrees. A simple device attached to the handle of an acetabular introducer can significantly improve the accuracy of implantation of a cemented cup into a saw bone pelvis in the lateral position.

Enhancing promiscuous chemistries of a Schiff-base forming enzyme by divergent evolution.

Directed evolution has emerged as a powerful technique for the rapid tailoring of enzymes toward particular synthetic demands, spawning a number of enzymes capable of complex chemical transformations. During random mutagenesis of a protein, changes in fitness must be assayed in order to quantify and understand the relative effect a given mutation has, and the assay employed must be carefully chosen to report directly on the transformation of interest. Here, we describe a series of medium-throughput screening techniques that have been utilized for the evolution and engineering of an artificial carboligase, RA95.5-8, resulting in improvement of catalytic efficiency of a number of promiscuous chemistries. The methods make use of common analytical chemistry equipment and low-cost materials, and may help inspire development of novel screening workflows for related transformations.

Universal 2 total wrist arthroplasty: high satisfaction but high complication rates.

The Universal 2 total wrist arthroplasty is intended to alleviate wrist pain and restore function. There is limited evidence regarding its success and safety. We report outcomes in 48 wrists of 46 patients with Universal 2 arthroplasty between 2006 and 2014. We recorded range of motion of the operated wrist, patient satisfaction, complication and revision rates, and radiological appearances of the wrists with mean follow-up of 7 years (3.5 to 11 years). We found a significant improvement in DASH scores after surgery, with active range of wrist motion being 33° flexion and 24° extension. Thirty-nine patients would undergo the procedure again if he had similar wrist problems. Twenty-three patients had loosening of at least one component of the implant. Complications were found in 13 wrists; seven underwent revision. We conclude that the Universal 2 arthroplasty produces significant improvements in DASH scores and high levels of satisfaction of the patients. However, the surgery has a high complication rate. LEVEL OF EVIDENCE: IV.

Rehabilitation regimens following surgical repair of extensor tendon injuries of the hand-a systematic review of controlled trials.

There is no consensus on the most effective rehabilitation regimen following extensor tendon repair of the hand. This systematic review evaluates the outcomes of the various regimens. The Cochrane, MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker databases were searched for any prospective randomised clinical trials comparing rehabilitation regimens for acute extensor tendon injuries in adults. Five papers met the inclusion criteria. The regimens were static immobilisation, dynamic splinting and early active motion (EAM). There was no standard format of reporting. The sample size ranged from 27 to 100 patients. The duration of follow-up ranged from 8 to 24 weeks. Overall, patients' total active motion improved with time. Early mobilisation regimens (active and passive) achieve quicker recovery of motion than static immobilisation but the long-term outcome appears similar. Given the comparable outcomes between dynamic splinting and EAM, we therefore favour EAM which is simpler and more convenient.

The differential diagnosis of foot lumps: 101 cases treated surgically in North Glasgow over 4 years.

INTRODUCTION: There are a wide variety of different lesions which present as lumps of the foot. There have been very few studies which look at the presenting characteristics or the differential diagnosis of such lesions. PATIENTS AND METHODS: All patients who underwent excision or biopsy of a foot lump over a period of 4 years were studied in order to determine patient demographics, presenting characteristics, diagnoses encountered and to assess the diagnostic accuracy of the surgeon. RESULTS: In total, 101 patients were identified. Average age was 47.3 years (range, 14-79 years); there was a marked female preponderance with 73 females and 28 males. Thirty different histological types were identified; ganglion cysts were the most commonly encountered lesions and there was only one malignant lesion encountered in this study. Only 58 out of the 101 lumps were correctly diagnosed prior to surgery. Certain lesions were more commonly encountered in specific zones of the foot. CONCLUSIONS: We have shown that there are a wide variety of potential diagnoses which have to be considered when examining a patient with a foot lump. There is a low diagnostic accuracy for foot lumps and, therefore, surgical excision and histological diagnosis should be sought if there is any uncertainty.

A new skatepark: the impact on the local hospital.

BACKGROUND: There has been a resurgence of skateboarding, rollerblading and BMX riding in recent years and in response dedicated skateparks have opened in many cities across the UK. It is acknowledged that these sports are associated with risk of injury and it is recommended that participants wear protective clothing. OBJECTIVE: We aimed to determine if the opening of a skatepark near our hospital had any effect on the number of skatepark related injuries attending the emergency department and to describe the types of injuries sustained. METHODS: All patients attending the emergency department with sports injuries were identified over 24 consecutive weeks. At the end of the 12th week a skatepark opened nearby. Data recorded prospectively included age and sex of subjects, the delay from injury to presenting to hospital, whether or not protective equipment was worn and if first aid was administered before attending hospital. The investigations performed in the emergency department, the diagnosis, treatment received and disposal from the hospital were also recorded. RESULTS: After the skatepark opened there was a significant increase in the number of skatepark related attendances from 7 to 32. Protective clothing was only worn by 9 out of 39 of those with injuries. The commonest injuries were musculoskeletal and the limbs were injured more frequently than the head and trunk. CONCLUSION: We demonstrated a significant increase in the number of skatepark related injuries attending the emergency department following the opening of a nearby skatepark.

One plunge or two?--hand disinfection with alcohol gel.

OBJECTIVE: To compare health care workers' hand surface coverage using two different volumes of alcohol gel for hand disinfection. PARTICIPANTS: and methods. A total of 84 members of staff in our hospital were studied. Subjects were asked to disinfect their hands with alcohol gel containing a clear fluorescent substance. Performance was assessed by using UV light to identify areas which had been missed, and the total surface area missed was calculated. A total of 42 subjects received 3.5 ml of alcohol gel, and 42 age-, sex-, and job-matched subjects received 1.75 ml of alcohol gel. RESULTS: Significantly less area was missed when hand disinfecting with double the volume of alcohol gel; 1.23 versus 6.35% surface area was missed (P < 0.001). CONCLUSION: Doubling the volume of alcohol gel used for hand disinfection significantly improves the efficiency of coverage of the hands with alcohol gel. This may result in lower bacterial count on the hands and may reduce the spread of nosocomial infections including that of methicillin-resistant Staphylococcus aureus.

Improving hand-washing performance - a crossover study of hand-washing in the orthopaedic department.

INTRODUCTION: Effective hand-washing is essential for reducing the spread of infection in hospitals. We aimed to evaluate hand-washing performance of hospital personnel and to determine if this could be improved by education. MATERIALS AND METHODS: A total of 55 personnel working in the orthopaedic department were asked to clean their hands using an alcohol gel containing a clear fluorescent substance. They were unaware of the assessment method. Performance was assessed by examining their hands under UV light to identify areas that had been neglected. Subjects could visualise which areas they had missed and were then educated regarding hand-washing technique and retested after 7 days. RESULTS: Of the 55 subjects, 53 completed the study. Individual performance varied widely. Following a simple educational intervention, 49 out of 53 subjects improved from an average of 7.8% to 2.3% area missed (P < 0.001). CONCLUSIONS: We suggest that hand-washing effectiveness needs to be improved and that a simple educational intervention can be effective.