Plastic physicians: The surgical salamanders of the COVID-19 pandemic.

At the time of writing, coronavirus disease-2019 (COVID-19) has affected 6.42 million people globally and over 380,000 deaths, with the United Kingdom now having the highest death rate in Europe. The plastic surgery department at Leeds Teaching Hospitals put necessary steps in place to maintain an excellent urgent elective and acute service whilst also managing COVID-positive medical patients in the ward. We describe the structures and pathways implemented together with complex decision-making, which has allowed us to respond early and effectively. We hope these lessons will prove a useful tool as we look to open conversations around the recovery of normal activity.

Tenosynovial giant cell tumours of the hand: A multicentre case-control study.

Many factors have been proposed to contribute to the risk of recurrent tenosynovial giant cell tumours (TSGCT); however, we remain unable to predict those at risk, which formed the rationale for this multicentre retrospective case-control study of 28 patients with recurrence. We included cases of recurrence in a 1:1 ratio matched for age and sex with controls over 10 years. Using Cox regression, we present hazard ratios (HRs) for recurrence with 95% confidence intervals (CIs). Out of 285 cases, 28 individuals developed recurrence after a median of 2.4 years. Recurrent TSGCT had a higher mitotic count/mm2 in the primary tumour (median increase of 3 [IQR 1, 7]). Mitotic count in the primary tumour was associated with the risk of recurrence (adjusted HR 1.1 [95% CI 1.1, 1.2]) meaning that for every additional mitosis, the risk of recurrence increased by 10% per annum. We recommend a prospective cohort study to validate our findings.

Extracellular vesicles induce protective immunity against Trichuris muris.

Gastrointestinal nematodes, such as Trichuris trichiura (human whipworm), are a major source of morbidity in humans and their livestock. There is a paucity of commercially available vaccines against these parasites, and vaccine development for T. trichiura has been impeded by a lack of known host protective antigens. Experimental vaccinations with T. muris (murine whipworm) soluble Excretory/Secretory (ES) material have demonstrated that it is possible to induce protective immunity in mice; however, the potential for extracellular vesicles (EVs) as a source of antigenic material has remained relatively unexplored. Here, we demonstrate that EVs isolated from T. muris ES can induce protective immunity in mice when administered as a vaccine without adjuvant and show that the protective properties of these EVs are dependent on intact vesicles. We also identified several proteins within EV preparations that are targeted by the host antibodies following vaccination and subsequent infection with T. muris. Many of these proteins, including VWD and vitellogenin N and DUF1943-domain-containing protein, vacuolar protein sorting-associated protein 52 and TSP-1 domain-containing protein, were detected in both soluble ES and EV samples and have homologues in other parasites of medical and veterinary importance, and as such are possible protective antigens.

Age and IQ Explained Working Memory Performance in a RCT with Fatty Fish in a Group of Forensic Inpatients.

OBJECTIVES: To investigate the effect of a long-term fatty fish intervention on a pure cognitive mechanism important for self-regulation and mental health, i.e. working memory (WM), controlling for age and IQ. DESIGN: A randomized controlled trial. SETTING: A forensic facility. PARTICIPANTS: Eighty-four young to middle aged male forensic inpatients with psychiatric disorders. INTERVENTION: Consumption of farmed salmon or control meal (meat) three times a week during 23 weeks. MEASUREMENT: Performance on WM tasks, both accuracy and mean reaction time, were recorded pre and post intervention. RESULTS: Performance on a cognitive functioning tasks taxing WM seemed to be explained by age and IQ. CONCLUSION: Fatty fish consumption did not improve WM performance in a group of young to middle aged adults with mental health problems, as less impressionable factors such as aging and intelligence seemed to be the key components. The present study improves the knowledge concerning the interaction among nutrition, health and the aging process.

A sticky end for gastrointestinal helminths; the role of the mucus barrier.

Gastrointestinal (GI) nematodes are a group of successful multicellular parasites that have evolved to coexist within the intestinal niche of multiple species. It is estimated that over 10% of the world's population are chronically infected by GI nematodes, making this group of parasitic nematodes a major burden to global health. Despite the large number of affected individuals, there are few effective treatments to eradicate these infections. Research into GI nematode infections has primarily focused on defining the immunological and pathological consequences on host protection. One important but neglected aspect of host protection is mucus, and the concept that mucus is just a simple barrier is no longer tenable. In fact, mucus is a highly regulated and dynamic-secreted matrix, underpinned by a physical hydrated network of highly glycosylated mucins, which is increasingly recognized to have a key protective role against GI nematode infections. Unravelling the complex interplay between mucins, the underlying epithelium and immune cells during infection are a major challenge and are required to fully define the protective role of the mucus barrier. This review summarizes the current state of knowledge on mucins and the mucus barrier during GI nematode infections, with particular focus on murine models of infection.

The balancing act of foraging: mammalian herbivores trade-off multiple risks when selecting food patches.

Animals face multiple risks while foraging such as the risk of acquiring inadequate energy from food and the risk of predation. We evaluated how two sympatric rabbits (pygmy rabbits, Brachylagus idahoensis, and mountain cottontail rabbits, Sylvilagus nuttallii) that differ in size, use of burrows, and habitat specialization in the sagebrush-steppe of western North America respond to different types and levels of perceived risks (i.e., fitness cost × probability of occurrence), including fiber and toxins in food, exposure to predation, and distance from a refuge. We measured food intake by the rabbits at paired food patches that varied in these risks and used the method of paired comparisons to create a relative ranking of habitat cues, which revealed an animal's perceived risk on a single scale representing an integrated response to a variety of risks. Pygmy rabbits perceived exposure to predation risk and distance from a burrow as riskier than did cottontails, whereas cottontails perceived dietary toxin as riskier. Pygmy rabbits consumed lower quality food, containing higher fiber or toxins, thereby avoided feeding in exposed patches or traveling far from their burrow to forage. In contrast, cottontails fed in exposed patches and traveled farther from the burrow to obtain higher quality food. We have shown how risks can be integrated into a single model that allows animals to reveal their perceptions of risks on a single scale that can be used to create a spatially explicit landscape of risk.

Antarctic ice sheet discharge driven by atmosphere-ocean feedbacks at the Last Glacial Termination.

Reconstructing the dynamic response of the Antarctic ice sheets to warming during the Last Glacial Termination (LGT; 18,000-11,650 yrs ago) allows us to disentangle ice-climate feedbacks that are key to improving future projections. Whilst the sequence of events during this period is reasonably well-known, relatively poor chronological control has precluded precise alignment of ice, atmospheric and marine records, making it difficult to assess relationships between Antarctic ice-sheet (AIS) dynamics, climate change and sea level. Here we present results from a highly-resolved 'horizontal ice core' from the Weddell Sea Embayment, which records millennial-scale AIS dynamics across this extensive region. Counterintuitively, we find AIS mass-loss across the full duration of the Antarctic Cold Reversal (ACR; 14,600-12,700 yrs ago), with stabilisation during the subsequent millennia of atmospheric warming. Earth-system and ice-sheet modelling suggests these contrasting trends were likely Antarctic-wide, sustained by feedbacks amplified by the delivery of Circumpolar Deep Water onto the continental shelf. Given the anti-phase relationship between inter-hemispheric climate trends across the LGT our findings demonstrate that Southern Ocean-AIS feedbacks were controlled by global atmospheric teleconnections. With increasing stratification of the Southern Ocean and intensification of mid-latitude westerly winds today, such teleconnections could amplify AIS mass loss and accelerate global sea-level rise.

Time-frequency analysis of the EEG mu rhythm as a measure of sensorimotor integration in the later stages of swallowing.

OBJECTIVE: Electroencephalography (EEG) was used to map the temporal dynamics of sensorimotor integration relative to the strength and timing of muscular activity during swallowing. METHODS: 64-channel EEG data and surface electromyographic (sEMG) data were recorded from 25 neurologically-healthy adults during swallowing and tongue-tapping. Events were demarcated so that sensorimotor activity primarily from the pharyngeal and esophageal phases of swallowing could be compared to activity resulting from tongue tapping. RESULTS: Independent component analysis identified bilateral clusters of sensorimotor mu components localized to the premotor and primary motor cortices as well as an infrahyoid myogenic cluster. Subsequent event-related spectral perturbations (ERSP) analyses showed event-related desynchronization (ERD) in the spectral power in the alpha (8-13Hz) and beta (15-25Hz) frequency bands of the mu clusters in both tasks. Mu ERD was stronger during swallowing when compared to tongue tapping (pFDR<.05) and the differences in sensorimotor processing between conditions was greater in the right hemisphere than the left, suggesting stronger right hemisphere lateralization for swallowing than tongue-tapping. CONCLUSION: Mu activity was interpreted as representing a normal feed forward and feedback driven sensorimotor loop during the later stages of swallowing. SIGNIFICANCE: Results support further use of this novel neuroimaging technique to concurrently map neural and muscle activity during swallowing in clinical populations using EEG.

Organising pneumonia due to dronedarone.

Organising pneumonia is one of the responses of the lung to injury and can mimic bacterial pneumonia but importantly it does not respond to antibiotic therapy. We present the case of a 67-year-old male who was diagnosed with organising pneumonia secondary to dronedarone. Drug reactions are a common cause and early identification of the culprit is mandatory to prevent further morbidity and ensure a favourable outcome. On chest radiography there may be fleeting peripheral consolidation, while computed tomography can show a range of stereotyped patterns including perilobular consolidation. Bronchoscopic biopsy may not always be possible but response to steroids is often rapid following removal of the culprit drug. Dronedarone should be included in the list of possible drugs and the Pneumotox database remains a useful resource for the clinician when acute drug-related pneumotoxicity is suspected.

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries.

OBJECTIVE: To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. DESIGN: Cross-country comparative study of linked population-based databases. SETTING: Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. POPULATION: All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995-2010). METHODS: Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). RESULTS: There were 9,028,802 deliveries (3,031,399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. CONCLUSION: Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia.

A population of fast radio bursts at cosmological distances.

Searches for transient astrophysical sources often reveal unexpected classes of objects that are useful physical laboratories. In a recent survey for pulsars and fast transients, we have uncovered four millisecond-duration radio transients all more than 40° from the Galactic plane. The bursts' properties indicate that they are of celestial rather than terrestrial origin. Host galaxy and intergalactic medium models suggest that they have cosmological redshifts of 0.5 to 1 and distances of up to 3 gigaparsecs. No temporally coincident x- or gamma-ray signature was identified in association with the bursts. Characterization of the source population and identification of host galaxies offers an opportunity to determine the baryonic content of the universe.

MRI of the reconstructed ulnar collateral ligament.

OBJECTIVE: We are often asked to evaluate the postoperative elbow using MRI. In this article, we present both the normal appearance of the reconstructed ulnar collateral ligament (UCL) and a spectrum of UCL graft abnormalities at MR arthrography. CONCLUSION: The UCL is the primary medial stabilizer of the elbow during flexion and is susceptible to injury, particularly in overhead throwing athletes. In the setting of UCL injury, ligament reconstruction is the principal surgical procedure available to restore stability and function and to relieve pain with activity. We have found MR arthrography useful in assessing the reconstructed UCL.

Changes in the mucosal barrier during acute and chronic Trichuris muris infection.

The intestinal mucosal barrier, part of the innate immune defence, is responsive to the external environment and changes in response to infection. There is disparate evidence for the epithelial and goblet cell products within the intrinsic barrier being part of a response to resolve infection. We comprehensively analysed the changes of mucosal glycoconjugates during acute and chronic infection by utilising the Trichuris muris (T. muris) model. Transcription factors, atonal homolog 1 (Math-1) and SAM pointed domain containing ETS transcription factor (Spdef) were activated during acute infection, which promoted stem cell fate towards a secretory cell phenotype. The thickness of the intermediate barrier, the carbohydrate-rich glycocalyx, composed of cell surface mucins increased with exposure to T. muris, with an increase in Muc4, Muc13 and Muc17. Overall, hypersecretion of glycoproteins into the extrinsic barrier (mediated by IL-13) via the gamma amino-butyric acid-α3 receptor (GABA-α3), was observed during acute infection. Furthermore, altered glycosylation was observed during acute and chronic infection; mucins were more highly charged during acute infection than during chronic infection. This study readdresses the changes within the mucosal barrier, in particular in the cell surface and secreted mucins during acute and chronic nematode infection.

Chronic suppurative otitis media in Nepal: ethnicity does not determine whether disease is associated with cholesteatoma or not.

OBJECTIVES: To determine the frequency of cholesteatoma in a population of patients with chronic suppurative otitis media, and to determine whether this frequency is affected by ethnicity. PATIENTS: The study included 6005 patients with chronic suppurative otitis media seen during the course of 30 charitable surgical 'ear camps' in Nepal. MAIN OUTCOME MEASURES: Proportion of patients with each subtype of disease, and their ethnicity. A secondary outcome measure was concordance of surname with Nepalese ethnic affiliation. RESULTS: A total of 762 patients were grouped as being of Tibeto-Mongolian origin, and 4875 as Indo-Caucasian. The rate of chronic suppurative otitis media with cholesteatoma, expressed as a proportion of the rate of all chronic suppurative otitis media subtypes, was 17.8 per cent in Tibeto-Mongolian patients and 18.6 per cent in Indo-Caucasian patients (p > 0.05). The effect of other risk factors (i.e. age, gender and geographical district) on disease distribution was also non-significant. Analysis of secondary outcome measures indicated that patients' surnames were a reliable predictor of ethnicity in this Nepalese population. CONCLUSION: There is almost complete concordance in proportions of patients with significant genetic, cultural, and even geographical heterogeneity, suggesting that, in Nepal, the aetiology of cholesteatoma owes little to these factors.

Phase Ib safety and pharmacokinetic evaluation of daily and twice daily oral enzastaurin in combination with pemetrexed in advanced/metastatic cancer.

BACKGROUND: This phase Ib study evaluated the safety, pharmacokinetics, and activity of enzastaurin either 500 mg once daily (QD) or 250 mg twice daily (b.i.d.) in combination with pemetrexed. PATIENTS AND METHODS: Pemetrexed 500 mg/m(2) with folic acid and vitamin B(12) was given on day 1 every 21 days with enzastaurin 500 mg orally QD starting on day 5 of cycle 1 after a loading dose of 400 mg thrice daily on day 4. To evaluate whether a b.i.d. regimen results in higher enzastaurin exposures, the study was amended. After amendment, in cycle 1, patients received 500 mg enzastaurin QD on days 1-15 without initial loading dose and 250 mg b.i.d. on days 16-30; in subsequent cycles, patients received pemetrexed on day 1 every 21 days with enzastaurin b.i.d. RESULTS: Sixty-eight patients (42 preamendment and 26 postamendment) were assessed. Pemetrexed toxicity and pharmacokinetics did not appear to be altered by enzastaurin. Enzastaurin average steady-state plasma concentration (C(av,ss)) decreased by approximately 25% in the presence of pemetrexed. Enzastaurin C(av,ss) were approximately 40% higher in the b.i.d. versus QD regimen. Three patients (4.4%) with thyroid cancer of follicular/papillary type had partial response as defined by RECIST. CONCLUSIONS: Pemetrexed plus enzastaurin is well tolerated with preliminary evidence of anticancer activity, particularly in thyroid cancer.

Avulsion of the medial epicondyle after ulnar collateral ligament reconstruction: imaging of a rare throwing injury.

OBJECTIVE: The objective of this article is to report and describe the clinical and imaging features of an avulsion fracture of the medial epicondyle after ulnar collateral ligament (UCL) reconstruction. CONCLUSION: Avulsion fracture of the medial epicondyle is a rare complication of UCL reconstruction with distinct radiographic and MRI findings.