The formation and function of the neutrophil phagosome.

Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate.

Room-Temperature Photochromism of Silicon Vacancy Centers in CVD Diamond.

The silicon vacancy (SiV) center in diamond is typically found in three stable charge states, SiV0, SiV-, and SiV2-, but studying the processes leading to their formation is challenging, especially at room temperature, due to their starkly different photoluminescence rates. Here, we use confocal fluorescence microscopy to activate and probe charge interconversion between all three charge states under ambient conditions. In particular, we witness the formation of SiV0 via the two-step capture of diffusing, photogenerated holes, a process we expose both through direct SiV0 fluorescence measurements at low temperatures and confocal microscopy observations in the presence of externally applied electric fields. In addition, we show that continuous red illumination induces the converse process, first transforming SiV0 into SiV- and then into SiV2-. Our results shed light on the charge dynamics of SiV and promise opportunities for nanoscale sensing and quantum information processing.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Management of complex regional pain syndrome in trauma and orthopaedic surgery-a systematic review.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a neurological pain disorder that is challenging to diagnose and manage, resulting in increased morbidity and costs. It most commonly occurs following traumatic injury, such as a fracture, crush injury or surgery. Recent research has evaluated the efficacy of treatments which have contradicted previous hypotheses. This systematic review summarizes these findings to improve clinician's decision-making. SOURCES OF DATA: A comprehensive search of PubMed, MEDLINE and Embase databases from inception through January 2021 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened relevant articles discussing the management of CRPS in adult trauma patients. All prospective and retrospective studies, non-randomized comparison studies and case series were considered for inclusion. Data extraction was performed by populating a predefined data abstraction sheet. AREAS OF AGREEMENT: There is strong evidence to suggest the efficacy of prompt physiotherapy, lidocaine, ketamine, bisphosphonates, sympathectomy and brachial plexus blocks in the management of CRPS. AREAS OF CONTROVERSY: The latest evidence suggests that vitamin C has no significant role to play in the treatment or prevention of CRPS. GROWING POINTS: A multidisciplinary team approach and early diagnosis are imperative for successful treatment of CRPS. The Budapest criteria and the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines should be used when diagnosing CRPS. There is currently no clear evidence of superiority in any treatment. AREAS TIMELY FOR DEVELOPING RESEARCH: There are few high-quality studies that inform the best treatment modalities for CRPS. Though emerging treatments show promise, further research is needed.

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

BACKGROUND: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19. OBJECTIVE: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups. DESIGN: Retrospective observational study utilizing electronic health record data from four health systems. SDoH variables analyzed included race, ethnicity, insurance, marital status, Area Deprivation Index, and population density. PARTICIPANTS: COVID-19 patients who met at least one emergency use authorization criterion for nMAb treatment. MAIN MEASURE: We used binary logistic regression to examine the influence of SDoH variables on receiving nMAb treatments and risk of a poor outcome from COVID-19 and marginal structural models to study treatment effectiveness. RESULTS: The study population included 25,241 (15.1%) nMAb-treated and 141,942 (84.9%) non-treated patients. Black or African American patients were less likely to receive treatment than white non-Hispanic patients (adjusted odds ratio (OR) = 0.86; 95% CI = 0.82-0.91). Patients who were on Medicaid, divorced or widowed, living in rural areas, or living in areas with the highest Area Deprivation Index (most vulnerable) had lower odds of receiving nMAb treatment, but a higher risk of a poor outcome. For example, compared to patients on private insurance, Medicaid patients had 0.89 (95% CI = 0.84-0.93) times the odds of receiving nMAb treatment, but 1.18 (95% CI = 1.13-1.24) times the odds of a poor COVID-19 outcome. Age, comorbidities, and COVID-19 vaccination status had a stronger influence on risk of a poor outcome than SDoH variables. nMAb treatment benefited all SDoH subgroups with lower rates of 14-day hospitalization and 30-day mortality. CONCLUSION: Disparities existed in receiving nMAbs within SDoH subgroups despite the benefit of treatment across subgroups.

There is a great variety of orthopaedic conditions presenting to a large hospital in Sierra Leone: a 3-year prospective study.

PURPOSE: In Sierra Leone there is a large void in orthopaedic research into the type of orthopaedic injuries, both acute and chronic. Improved data collection is essential in providing insight to guide health care planning and research. This study aims to outline the types of orthopaedic injury sustained. METHOD: Data were prospectively collected by local surgeons in the Orthopaedic outpatient department at a large hospital between January 2016 and January 2019. RESULTS: The orthopaedic department saw a mean 728 patients per year, with mean age 24.0 years. The workload comprised of 64.92% acute orthopaedic conditions or their complications, with 35.08% elective orthopaedics. Fractures made up the largest proportion of clinical appointments, annually 244.33 fractures; however there was a high incidence of osteomyelitis. CONCLUSION: The study gives an important insight into the types and distribution of elective and trauma orthopaedic injuries sustained in Sierra Leone, which has not been previously reported, and highlights key areas where resources may be focused in order to improve clinical outcomes.

Vessel segmentation for X-ray coronary angiography using ensemble methods with deep learning and filter-based features.

BACKGROUND: Automated segmentation of coronary arteries is a crucial step for computer-aided coronary artery disease (CAD) diagnosis and treatment planning. Correct delineation of the coronary artery is challenging in X-ray coronary angiography (XCA) due to the low signal-to-noise ratio and confounding background structures. METHODS: A novel ensemble framework for coronary artery segmentation in XCA images is proposed, which utilizes deep learning and filter-based features to construct models using the gradient boosting decision tree (GBDT) and deep forest classifiers. The proposed method was trained and tested on 130 XCA images. For each pixel of interest in the XCA images, a 37-dimensional feature vector was constructed based on (1) the statistics of multi-scale filtering responses in the morphological, spatial, and frequency domains; and (2) the feature maps obtained from trained deep neural networks. The performance of these models was compared with those of common deep neural networks on metrics including precision, sensitivity, specificity, F1 score, AUROC (the area under the receiver operating characteristic curve), and IoU (intersection over union). RESULTS: With hybrid under-sampling methods, the best performing GBDT model achieved a mean F1 score of 0.874, AUROC of 0.947, sensitivity of 0.902, and specificity of 0.992; while the best performing deep forest model obtained a mean F1 score of 0.867, AUROC of 0.95, sensitivity of 0.867, and specificity of 0.993. Compared with the evaluated deep neural networks, both models had better or comparable performance for all evaluated metrics with lower standard deviations over the test images. CONCLUSIONS: The proposed feature-based ensemble method outperformed common deep convolutional neural networks in most performance metrics while yielding more consistent results. Such a method can be used to facilitate the assessment of stenosis and improve the quality of care in patients with CAD.

Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades.Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function.Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population.

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus.

OBJECTIVES: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. METHODS: Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. RESULTS: Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. CONCLUSIONS: Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy.

The spatial distribution of thin filament activation influences force development and myosin activity in computational models of muscle contraction.

Striated muscle contraction is initiated by Ca2+ binding to, and activating, thin filament regulatory units (RU) within the sarcomere, which then allows myosin cross-bridges from the opposing thick filament to bind actin and generate force. The amount of overlap between the filaments dictates how many potential cross-bridges are capable of binding, and thus how force is generated by the sarcomere. Myopathies and atrophy can impair muscle function by limiting cross-bridge interactions between the filaments, which can occur when the length of the thin filament is reduced or when RU function is disrupted. To investigate how variations in thin filament length and RU density affect ensemble cross-bridge behavior and force production, we simulated muscle contraction using a spatially explicit computational model of the half-sarcomere. Thin filament RUs were disabled either uniformly from the pointed end of the filament (to model shorter thin filament length) or randomly throughout the length of the half-sarcomere. Both uniform and random RU 'knockout' schemes decreased overall force generation during maximal and submaximal activation. The random knockout scheme also led to decreased calcium sensitivity and cooperativity of the force-pCa relationship. We also found that the rate of force development slowed with the random RU knockout, compared to the uniform RU knockout or conditions of normal RU activation. These findings imply that the relationship between RU density and force production within the sarcomere involves more complex coordination than simply the raw number of RUs available for myosin cross-bridge binding, and that the spatial pattern in which activatable RU are distributed throughout the sarcomere influences the dynamics of force production.

Characteristics of L-PRP preparations for treating Achilles tendon rupture within the PATH-2 study.

Platelet-rich plasma (PRP) is an autologous preparation that has been claimed to improve healing and mechanobiological properties of tendons both in vitro and in vivo. In this sub-study from the PATH-2 (PRP in Achilles Tendon Healing-2) trial, we report the cellular and growth factor content and quality of the Leukocyte-rich PRP (L-PRP) (N = 103) prepared using a standardized commercial preparation method across 19 different UK centers. Baseline whole blood cell counts (red cells, leukocyte and platelets) demonstrated that the two groups were well-matched. L-PRP analysis gave a mean platelet count of 852.6 x 109/L (SD 438.96), a mean leukocyte cell count of 15.13 x 109/L (SD 10.28) and a mean red blood cell count of 0.91 x 1012/L (SD 1.49). The activation status of the L-PRP gave either low or high expression levels of the degranulation marker CD62p before and after ex-vivo platelet activation respectively. TGF-ß, VEGF, PDGF, IGF and FGFb mean concentrations were 131.92 ng/ml, 0.98 ng/ml, 55.34 ng/ml, 78.2 ng/ml and 111.0 pg/ml respectively with expected correlations with both platelet and leukocyte counts. While PATH-2 results demonstrated that there was no evidence L-PRP is effective for improving clinical outcomes at 24 weeks after Achilles tendon rupture, our findings support that the majority of L-PRP properties were within the method specification and performance.

Automated Spleen Injury Detection Using 3D Active Contours and Machine Learning.

The spleen is one of the most frequently injured organs in blunt abdominal trauma. Computed tomography (CT) is the imaging modality of choice to assess patients with blunt spleen trauma, which may include lacerations, subcapsular or parenchymal hematomas, active hemorrhage, and vascular injuries. While computer-assisted diagnosis systems exist for other conditions assessed using CT scans, the current method to detect spleen injuries involves the manual review of scans by radiologists, which is a time-consuming and repetitive process. In this study, we propose an automated spleen injury detection method using machine learning. CT scans from patients experiencing traumatic injuries were collected from Michigan Medicine and the Crash Injury Research Engineering Network (CIREN) dataset. Ninety-nine scans of healthy and lacerated spleens were split into disjoint training and test sets, with random forest (RF), naive Bayes, SVM, k-nearest neighbors (k-NN) ensemble, and subspace discriminant ensemble models trained via 5-fold cross validation. Of these models, random forest performed the best, achieving an Area Under the receiver operating characteristic Curve (AUC) of 0.91 and an F1 score of 0.80 on the test set. These results suggest that an automated, quantitative assessment of traumatic spleen injury has the potential to enable faster triage and improve patient outcomes.

Return to sport following Lisfranc injuries: A systematic review and meta-analysis.

BACKGROUND: Information regarding return rates (RR) and mean return times (RT) to sport following Lisfranc injuries remains limited. METHODS: A systematic search of nine major databases was performed to identify all studies which recorded RR or RT to sport following lisfranc injuries. RESULTS: Seventeen studies were included (n=366). For undisplaced (Stage 1) injuries managed nonoperatively (n=35), RR was 100% and RT was 4.0 (0-15) wks. For stable minimally-displaced (Stage 2) injuries managed nonoperatively (n=16), RR was 100% and RT was 9.1 (4-14) wks. For the operatively-managed injuries, Percutaneous Reduction Internal Fixation (PRIF) (n=42), showed significantly better RR and RT compared to both: Open Reduction Internal Fixation (ORIF) (n=139) (RR - 98% vs 78%, p<0.019; RT - 11.6 wks vs 19.6 wks, p<0.001); and Primary Partial Arthrodesis (PPA) (n=85) (RR - 98% vs 85%, p<0.047; RT - 11.6 wks vs 22.0 wks, p<0.002). CONCLUSIONS: Stage 1 and stable Stage 2 Lisfranc injuries show good results with nonoperative management. PRIF offers the best RR and RT from the operative methods, though this may not be possible with high-energy injuries. LEVEL OF EVIDENCE: IV. Systematic Review of Level I to Level IV Studies.

C5a anaphylatoxin and its role in critical illness-induced organ dysfunction.

Critical illness is an aetiologically and clinically heterogeneous syndrome that is characterised by organ failure and immune dysfunction. Mortality in critically ill patients is driven by inflammation-associated organ damage and a profound vulnerability to nosocomial infection. Both factors are influenced by the activated complement protein C5a, released by unbridled activation of the complement system during critical illness. C5a exerts deleterious effects on organ systems directly and suppresses antimicrobial functions of key immune cells. Whilst several recent reports have added key knowledge of the cellular signalling pathways triggered by C5a, there remain a number of areas that are incompletely understood and therapeutic opportunities are still being evaluated. In this review, we summarise the cellular basis for C5a-induced vulnerability to nosocomial infection and organ dysfunction. We focus on cells of the innate immune system, highlighting the major areas in need of further research and potential avenues for targeted therapies.

Excellent Survival and Good Outcomes at 15 Years Using the Press-Fit Condylar Sigma Total Knee Arthroplasty.

BACKGROUND: We report 15-year survival, clinical, and radiographic follow-up data for the Press-Fit Condylar Sigma total knee arthroplasty. METHODS: Between October 1998 and October 1999, 235 consecutive TKAs were performed in 203 patients. Patients were reviewed at a specialist nurse-led clinic before surgery and at 5, 8-10, and 15 years postoperatively. Clinical outcomes, including Knee Society Score, were recorded prospectively at each clinic visit, and radiographs were obtained. RESULTS: Of our initial cohort, 99 patients (118 knees) were alive at 15 years, and 31 patients (34 knees) were lost to follow-up. Thirteen knees (5.5%) were revised; 5 (2.1%) for infection, 7 (3%) for instability, and 1 (0.4%) for aseptic loosening. Cumulative survival with the end point of revision for any reason was 92.3% at 15 years and with revision for aseptic failure as the end point was 94.4%. The mean Knee Society Score knee score was 77.4 (33-99) at 15 years, compared with 31.7 (2-62) preoperatively. Of 71 surviving knees for which X-rays were available, 12 (16.9%) had radiolucent lines and 1 (1.4%) demonstrated clear radiographic evidence of loosening. CONCLUSION: The Press-Fit Condylar Sigma total knee arthroplasty represents a durable, effective option for patients undergoing knee arthroplasty, with excellent survival and good clinical and radiographic outcomes at 15 years.

Using a Model to Understand the Symptoms of Ophthalmoplegia.

When the term muscular paralysis is used, most people will think of large muscle groups such as the upper and lower limbs or life-dependent muscles such as the diaphragm. However, the extrinsic extraocular muscles can also succumb to paralysis (whether partial or otherwise). Ophthalmoplegia can arise from a number of neural conditions, and in conjunction with the complex anatomy of the ocular orbit, it can be difficult to teach such syndromes. The range of existing physical models for the eye are limited in their functional ability, prohibiting the understanding of the structure and its function especially with regards to muscles. Only one eye model has been developed which is tangible and functional by design in relation to rotational movements (Williams, 1965). The aim of this study was to ultimately build a modern version of Williams' model and via means of a Likert-type, cross-sectional questionnaire, determine the model's capacity to assist students in learning the function and anatomy of the extrinsic muscles of the eye. This foundational knowledge could then be transferred to better understand the internal causes of the visible symptoms of ophthalmoparesis and ophthalmoplegia. In much the same way that different diagnostic scans are used to observe different bodily materials, functional models may not necessarily replace the range of anatomical resources which exist, but it is hoped that models such as this will instead provide insight into an alternative aspect of anatomical learning which is yet to be considered.

Adenylation Activity of Carboxylic Acid Reductases Enables the Synthesis of Amides.

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids to aldehydes using the cofactors adenosine triphosphate and nicotinamide adenine dinucleotide phosphate, and have become attractive biocatalysts for organic synthesis. Mechanistic understanding of CARs was used to expand reaction scope, generating biocatalysts for amide bond formation from carboxylic acid and amine. CARs demonstrated amidation activity for various acids and amines. Optimization of reaction conditions, with respect to pH and temperature, allowed for the synthesis of the anticonvulsant ilepcimide with up to 96 % conversion. Mechanistic studies using site-directed mutagenesis suggest that, following initial enzymatic adenylation of substrates, amidation of the carboxylic acid proceeds by direct reaction of the acyl adenylate with amine nucleophiles.

Freezing and non-freezing cold weather injuries: a systematic review.

INTRODUCTION: The debilitating impact of cold weather on the human body is one of the world's oldest recorded injuries. The severe and life-changing damage which can be caused is now more commonly seen recreationally in extreme outdoor sports rather than in occupational settings such as the military. The diagnosis and treatment of these injuries need to be completed carefully but quickly to reduce the risk of loss of limb and possibly life. Therefore, we have conducted a systematic review of the literature surrounding cold weather injuries (CWIs) to ascertain the epidemiology and current management strategies. SOURCES OF DATA: Medline (PubMED), EMBASE, CINHAL, Cochrane Collaboration Database, Web of Science, Scopus and Google Scholar. AREAS OF AGREEMENT IMMEDIATE FIELD TREATMENT: The risk of freeze thaw freeze injuries. Delayed surgical intervention when possible. Different epidemiology of freezing and non-freezing injuries. AREAS OF CONTROVERSY: Prophylatic use of antibiotics; the use of vasodilators surgical and medical. GROWING POINTS: The use of ilioprost and PFG2a for the treatment of deep frostbite. AREAS TIMELY FOR DEVELOPING RESEARCH: The treatment of non-freezing CWIs with their long-term follow-up.

The importance of the orthopaedic doctors' appearance: a cross-regional questionnaire based study.

OBJECTIVES: Critics of the Department of Health 'bare below the elbow' guidelines have raised concerns over the impact of these dress regulations on the portrayed image and professionalism of doctors. However, the importance of the doctor's appearance in relation to other professional attributes is largely unknown. The purpose of this study was to determine the opinion of patients on the importance of appearance and the style of clothing worn by doctors. DESIGN: Patient questionnaire survey, administered across four Scottish regions. SETTING: Orthopaedic outpatient departments. PARTICIPANTS: 427 patients and accompanying relatives. MAIN OUTCOME MEASURES: The absolute and relative importance of the doctors' appearance, as reported using a 5-point Likert scale. The absolute and relative importance of the style of clothing worn by doctors, as reported using a 5-point Likert scale. The rank preferences for four different styles of doctors' attire as illustrated by standardised clinical photographs. RESULTS: The study was appropriately powered to identify a 0.5 difference in mean rank values with 0.90 power at a = 0.05. The majority of participants felt the doctors' appearance was important but not as important as compassion, politeness and knowledge. Only 50% felt that the style of doctors clothing mattered; what proved more important was an impression of cleanliness and good personal hygiene. In terms of how patients would prefer doctors to dress in clinic, the most popular choice proved to be the smart casual style of dress, which conforms with the 'bare below the elbows' dress code policy. The smart casual clothing style was the highest ranked choice irrespective of patient age, gender, regional or socioeconomic background. CONCLUSIONS: The doctors' appearance is of importance to patients and their relatives, but they view many other attributes as more important than how we choose to dress. While not specifically addressing the role of doctors clothing in the transmission of infection, our results do support the preference of patients for 'bare below the elbows' workplace attire.