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Aim: We previously reported sensitivity and specificity levels of the general movements assessment (GMA) to detect cerebral palsy (CP) at 1 year within a clinical setting and with the assistance of the New South Wales (NSW) Rater Network. The aim of this study was to determine whether similarly high levels of validity could be maintained in the same group at 2 years., Methods: A prospective longitudinal cross-sectional study was conducted. GMA was blind-rated from conventional video by two independent certified raters, blinded to medical history. A third rater resolved disagreements. High-risk population screening for CP using the GMA during the fidgety period (12-20 weeks) was carried out in four neonatal intensive care units and one CP service over a 30-month period. Participants were 259 high-risk infants for the initial study. Multidisciplinary follow-up at 2-3 years included Bayley Scales of Infant Development and confirmed diagnosis of CP. Sensitivity and specificity values were calculated with true positives defined as a confirmed diagnosis of CP., Results: At 2-3 years, 184 (71%) completed the follow-up assessment. GMA was normal for 134 (73%, low risk for CP), absent fidgety for 48 (26%, high risk for CP) and abnormal fidgety for 2 (1%, high risk for abnormal neurological disorder). Sensitivity for detecting CP was 97.6% (40/41) and specificity 95.7% (133/139). Sensitivity for detecting any abnormal outcome with absent/abnormal fidgety general movements (GMs) was 57.9% (44/76) and specificity 94.4% (101/107)., Conclusion: Excellent levels of sensitivity and specificity of the GMA for detecting CP in the clinical setting were maintained at 2 years and were similar to our previously reported findings., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: The Emergency Surgery Score (ESS) was recently developed and retrospectively validated as an accurate mortality risk calculator for emergency general surgery. We sought to prospectively validate ESS, specifically in the high-risk nontrauma emergency laparotomy (EL) patient., Methods: This is an Eastern Association for the Surgery of Trauma multicenter prospective observational study. Between April 2018 and June 2019, 19 centers enrolled all adults (aged >18 years) undergoing EL. Preoperative, intraoperative, and postoperative variables were prospectively and systematically collected. Emergency Surgery Score was calculated for each patient and validated using c-statistic methodology by correlating it with three postoperative outcomes: (1) 30-day mortality, (2) 30-day complications (e.g., respiratory/renal failure, infection), and (3) postoperative intensive care unit (ICU) admission., Results: A total of 1,649 patients were included. The mean age was 60.5 years, 50.3% were female, and 71.4% were white. The mean ESS was 6, and the most common indication for EL was hollow viscus perforation. The 30-day mortality and complication rates were 14.8% and 53.3%; 57.0% of patients required ICU admission. Emergency Surgery Score gradually and accurately predicted 30-day mortality; 3.5%, 50.0%, and 85.7% of patients with ESS of 3, 12, and 17 died after surgery, respectively, with a c-statistic of 0.84. Similarly, ESS gradually and accurately predicted complications; 21.0%, 57.1%, and 88.9% of patients with ESS of 1, 6, and 13 developed postoperative complications, with a c-statistic of 0.74. Emergency Surgery Score also accurately predicted which patients required intensive care unit admission (c-statistic, 0.80)., Conclusion: This is the first prospective multicenter study to validate ESS as an accurate predictor of outcome in the EL patient. Emergency Surgery Score can prove useful for (1) perioperative patient and family counseling, (2) triaging patients to the intensive care unit, and (3) benchmarking the quality of emergency general surgery care., Level of Evidence: Prognostic study, level III.

Objective: Proper use of automobile seat belt in a motor vehicle crash is associated with reduced morbidity and mortality, shorter hospital stays, reduced resource utilization, and fewer missed work days. Seatbelt compliance nationwide is 86%. This study was undertaken to identify factors associated with noncompliance with seatbelt use among admitted patients following a motor vehicle crash., Methods: This study was a retrospective analysis of motor vehicle crashes at an Urban Level 1 Trauma Center. Eligible subjects included patients age 18 and over, who were admitted by the Trauma Service following a motor vehicle crash from January to December 2017., Results: Among 766 participants, the overall rate of seatbelt noncompliance was 32% (N = 245). Some participants met the legal limit of intoxication (80 mg/dl) (N = 119 patients; 22%). Drug use was high among this population, including THC (30%), opiates (29%), benzodiazepines (24%), cocaine (10%), and methamphetamine (10%). Patients who did not wear seat belts were more likely to be male (62.4% no seat belt vs. 51.8% seat belt), intoxicated (30.5% vs. 17.0%), screen positive for cocaine (18.2% vs. 4.7%), THC (37.7% vs. 24.2%), and methamphetamine (15.6% vs. 5.9%). We did not detect significant differences by seat belt use with respect to ethnicity, mode of arrival, day of week, opiate use, or benzodiazepine use., Conclusions: In this study, 32% of patients in motor vehicle crashes were not compliant with seat belt use. Noncompliance with seat belt use was higher among patients who were male, younger age, intoxicated, or who had positive screens for cocaine, THC, or methamphetamine., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies.

Introduction: Pneumonia is a known complication following rib fractures. This study was undertaken to identify clinical and demographic factors associated with the development of pneumonia among trauma patients with rib fractures., Methods: This retrospective study examined trauma patients with one or more rib fractures, who were admitted for inpatient management during the time period 2012 through 2017. Variables studied included age, gender, injury severity score (ISS), mechanism of injury, smoking status, alcohol use, administration of influenza and pneumococcal vaccine, number and side of rib fracture(s), pulmonary contusion, pneumothorax, flail chest, spirometer use, blood transfusion, and intravenous fluid administration., Results: Among 78 cases and 74 controls (matched for age and ISS), patients who developed pneumonia were more likely to be male, have higher number of rib fractures, alcohol consumption of 1-5 drinks per day, and a higher initial volume of intravenous fluids during first 24 h. Patients with pneumonia were more likely to be treated with incentive spirometry. There were no difference in age, ISS, smoking status, side of rib fractures, pulmonary contusion, pneumothorax, flail chest, influenza vaccination, pneumonia vaccination, or mechanism of injury between the two groups., Conclusion: Risk factors for the development of pneumonia following rib fractures include male gender, higher number of rib fractures, alcohol consumption, and higher rates of intravenous fluid administration during the initial 24 h following trauma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Geriatric patients (age >65) comprise a growing segment of the trauma population. New-onset atrial fibrillation may occur after injury, complicating clinical management and resulting in significant morbidity and mortality. This study was undertaken to identify clinical and demographic factors associated with new-onset atrial fibrillation among geriatric trauma patients., Methods: In this case control study, eligible participants included admitted trauma patients age 65 and older who developed new-onset atrial fibrillation during the hospitalization. Controls were admitted trauma patients who were matched for age and injury severity score, who did not develop atrial fibrillation. We evaluated the associations between new-onset atrial fibrillation and clinical characteristics, including patient demographics, health behaviors, chronic medical conditions, and course of care., Results: Data were available for 63 cases and 25 controls. Patients who developed atrial fibrillation were more likely to be male, compared to controls (49% versus 24%; odds ratio 3.0[1.0, 8.9]). Other demographic and clinical factors were not associated with new-onset atrial fibrillation, including mechanism of injury, co-morbid medical conditions, drug or alcohol use, surgical procedures, and intravenous fluid administration., Conclusions: Male geriatric trauma patients were at higher risk for developing new-onset atrial fibrillation. Other demographic and clinical factors were not associated with new-onset atrial fibrillation., Competing Interests: The authors report no conflicts of interest., (© 2019 The Authors. JACEP Open published by Wiley Periodicals, Inc. on behalf of the American College of Emergency Physicians.)

Road traffic injuries are a neglected global public health problem. Over 1.25 million people are killed each year, and middle-income countries, which are motorising rapidly, are the hardest hit. Sri Lanka is dealing with an injury-related healthcare crisis, with a recent 85% increase in road traffic fatality rates. Road traffic crashes now account for 25 000 injuries annually and 10 deaths daily. Development of a trauma registry is the foundation for injury control, care and prevention. Five northern Sri Lankan provinces collaborated with Jaffna Teaching Hospital to develop a local electronic registry. The Centre for Clinical Excellence and Research was established to provide organisational leadership, hardware and software were purchased, and data collectors trained. Initial data collection was modified after implementation challenges were resolved. Between 1 June 2017 and 30 September 2017, 1708 injured patients were entered into the registry. Among these patients, 62% were male, 76% were aged 21-50, 71.3% were motorcyclists and 34% were in a collision with another motorcyclist. There were frequent collisions with uncontrolled livestock (12%) and with fixed objects (14%), and most patients were transported by private vehicles without prehospital care. Head (n=315) and lower extremity (n=497) injuries predominated. Establishment of a trauma registry in low-income and middle-income countries is a significant challenge and requires invested local leadership; the most challenging issue is ongoing funding. However, this pilot registry provides a valuable foundation, identifying unique injury mechanisms, establishing priorities for prevention and patient care, and introducing the concept of an organised system to this region., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Protein primary structure is a potential critical quality attribute for biotherapeutics. Identifying and characterizing any sequence variants present is essential for product development. A sequence variant ~11 kDa larger than the expected IgG mass was observed by size-exclusion chromatography and two-dimensional liquid chromatography coupled with online mass spectrometry. Further characterization indicated that the 11 kDa was added to the heavy chain (HC) Fc domain. Despite the relatively large mass addition, only one unknown peptide was detected by peptide mapping. To decipher the sequence, the transcriptome of the manufacturing cell line was characterized by Illumina RNA-seq. Transcriptome reconstruction detected an aberrant fusion transcript, where the light chain (LC) constant domain sequence was fused to the 3' end of the HC transcript. Translation of this fusion transcript generated an extended peptide sequence at the HC C-terminus corresponding to the observed 11 kDa mass addition. Nanopore-based genome sequencing showed multiple copies of the plasmid had integrated in tandem with one copy missing the 5' end of the plasmid, deleting the LC variable domain. The fusion transcript was due to read-through of the HC terminator sequence into the adjacent partial LC gene and an unexpected splicing event between a cryptic splice-donor site at the 3' end of the HC and the splice acceptor site at the 5' end of the LC constant domain. Our study demonstrates that combining protein physicochemical characterization with genomic and transcriptomic analysis of the manufacturing cell line greatly improves the identification of sequence variants and understanding of the underlying molecular mechanisms.

Competing Interests: Competing interests: None declared.

Food-related attentional bias (AB) varies both between individuals (i.e. trait differences) and within individuals (i.e. state differences), as a function of a food's momentary incentive value. People with self-perceived food addiction (SPFA) find food particularly rewarding and may therefore demonstrate increased AB to food-related cues, relative to those who do not perceive themselves as food addicts. However, these trait differences may interact with state factors, such as hunger and the perceived availability of food, to differentially affect AB to food-cues. In the current study, female participants (N = 120) completed an eye-tracking task to assess AB to chocolate pictures in which the expectancy of receiving chocolate was manipulated on a trial-by-trial basis (0%, 50%, 100%). Participants were randomly allocated such that half completed the task when hungry (hungry condition), and half completed the task following a lunch meal (satiated condition). Participants also indicated the extent to which they perceived themselves to be 'food addicts' (SPFAs: n = 37; Non-addicts: n = 53; Undecided: n = 28). Consistent with previous findings, there was a significant main effect of chocolate expectancy; food-related AB was greater on 100% and 50% trials, compared to 0% trials. However, there was no effect of hunger condition (hungry vs. satiated) on AB. Contrary to our hypotheses, SPFAs did not show increased AB to food-cues, and this was not moderated by hunger condition or the expectancy information. Exploratory analyses revealed that higher desire-to-eat (DtE) chocolate was associated with increased AB to chocolate pictures. These findings partially support contemporary theoretical models of AB by indicating a key role for state factors (reward expectancy, DtE) in determining AB to food-cues, while a trait factor (SPFA) was not a significant determinant of food AB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Selecting the most appropriate protein sequences is critical for precision drug design. Here we describe Haplosaurus, a bioinformatic tool for computation of protein haplotypes. Haplosaurus computes protein haplotypes from pre-existing chromosomally-phased genomic variation data. Integration into the Ensembl resource provides rapid and detailed protein haplotypes retrieval. Using Haplosaurus, we build a database of unique protein haplotypes from the 1000 Genomes dataset reflecting real-world protein sequence variability and their prevalence. For one in seven genes, their most common protein haplotype differs from the reference sequence and a similar number differs on their most common haplotype between human populations. Three case studies show how knowledge of the range of commonly encountered protein forms predicted in populations leads to insights into therapeutic efficacy. Haplosaurus and its associated database is expected to find broad applications in many disciplines using protein sequences and particularly impactful for therapeutics design.

Chiral 2-substituted-6-methyl 2,3-dihydropyidinones 9, which can be facilely obtained from an asymmetric vinylogous Mannich reaction (VMR) with 1,3-bis-trimethysily enol ether, were used as versatile intermediates in constructing chiral polyfunctional piperidine-based compounds. The 6-methyl group of such compounds can be conveniently functionalized via alkylation and acylation reactions to provide efficient entries to the synthesis of a variety of chiral multi-substituted piperidine-based compounds. Further elaboration of the corresponding intermediates also provided access to polyfunctional indolizidine-based compounds. These methods were showcased in an asymmetric synthesis of 2,6-di-substituted piperidine compound 13, reported as the key intermediate in the synthesis of (+)-calvine and a natural alkaloid (-)-indolizidine 209D. Furthermore, selective C5 iodination of compound 9 enabled the installation of additional functional groups at this position. Finally, we demonstrated that the oxidative cleavage of 2-substituted-6-methyl-2,3-dihydropyidinones is a practical and efficient method for the enantioselective synthesis of β-amino acids, which can undergo further intra-molecular cyclization to give the corresponding chiral four-membered β-lactam derivatives.

High levels of protein expression are key to the successful development and manufacture of a therapeutic antibody. Here, we describe two related antibodies, Ab001 and Ab008, where Ab001 shows a markedly lower level of expression relative to Ab008 when stably expressed in Chinese hamster ovary cells. We use single-gene expression vectors and structural analysis to show that the reduced titer is associated with the VL CDR2 of Ab001. We adopted two approaches to improve the expression of Ab001. First, we used mutagenesis to change single amino-acid residues in the Ab001 VL back to the equivalent Ab008 residues but this resulted in limited improvements in expression. In contrast when we used an in silico structure-based design approach to generate a set of five individual single-point variants in a discrete region of the VL, all exhibited significantly improved expression relative to Ab001. The most successful of these, D53N, exhibited a 25-fold increase in stable transfectants relative to Ab001. The functional potency of these VL-modified antibodies was unaffected. We expect that this in silico engineering strategy can be used to improve the expression of other antibodies and proteins., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures., Methods/design: A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n=116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n=50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken., Discussion: The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour., Trial Registration: Clinical Trials: NCT02591134; registered: 23.10.2015., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Bees are one of the most well-known and important type of pollinators in agriculture and natural ecosystems, and maintaining their diversity in nature is essential. In this study, we report the complete mitochondrial genome of Hylaeus dilatatus, the first mitochondrial genome of Colletidae. Its complete mtDNA sequence is 15,475 bp in length, which contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one control region. The base composition of mtDNA is 44.27% A, 41.52% T, 8.80% C and 5.41% G. The percentage of A + T is 85.79%. The first complete mitogenome of Colletidae family could be used in studies of molecular systematics, conservation genetics, and stock evaluation.

Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A 2 (PLA 2 ) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. In this study, we observed expression of a cytoplasmic PLA 2 (PLA2G4D) in psoriatic mast cells but, unexpectedly, also found PLA2G4D activity to be extracellular. This was explained by IFN-α-induced mast cell release of exosomes, which transferred cytoplasmic PLA 2 activity to neighboring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid-specific CD1a-reactive T cells inducing production of IL-22 and IL-17A. Circulating and skin-derived T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared with healthy controls. Overall, these data present an alternative model of psoriasis pathogenesis in which lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA 2 inhibition or CD1a blockade may have therapeutic potential for psoriasis., (© 2016 Cheung et al.)

IL-33 is the most recent addition to the IL-1 cytokine family, identified in 2005 as the ligand of T1/ST2 and inducer of type-2 immune responses. IL-33 has been implicated in a wide range of disease settings, in anti-inflammatory responses and homeostasis, and thus signalling must be strictly regulated. Altered gene expression, post-translational modification, decoy receptor, and receptor signalling are all modulatory mechanisms used to control the IL-33 pathway. Understanding both the genetic and post-translational factors influencing IL-33 activity will be critical for provision of safe effective treatment of type-2 disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Atopic dermatitis is a common pruritic skin disease in which barrier dysfunction and cutaneous inflammation contribute to pathogenesis. Mechanisms underlying the associated inflammation are not fully understood, and although Langerhans cells expressing the nonclassical major histocompatibility complex (MHC) family member CD1a are known to be enriched within lesions, their role in clinical disease pathogenesis has not been studied. We observed that house dust mite (HDM) allergen generates neolipid antigens presented by CD1a to T cells in the blood and skin lesions of affected individuals. HDM-responsive CD1a-reactive T cells increased in frequency after birth in individuals with atopic dermatitis and showed rapid effector function, consistent with antigen-driven maturation. In HDM-challenged human skin, we observed phospholipase A2 (PLA2) activity in vivo. CD1a-reactive T cell activation was dependent on HDM-derived PLA2, and such cells infiltrated the skin after allergen challenge. Moreover, we observed that the skin barrier protein filaggrin, insufficiency of which is associated with atopic skin disease, inhibited PLA2 activity and decreased CD1a-reactive PLA2-generated neolipid-specific T cell activity from skin and blood. The most widely used classification schemes of hypersensitivity suggest that nonpeptide stimulants of T cells act as haptens that modify peptides or proteins; however, our results show that HDM proteins may also generate neolipid antigens that directly activate T cells. These data define PLA2 inhibition as a function of filaggrin, supporting PLA2 inhibition as a therapeutic approach., (Copyright © 2016, American Association for the Advancement of Science.)

Aim: The aim of this study was to calculate the sensitivity and specificity of the General Movements Assessment (GMA) for estimating diagnostic accuracy in detecting cerebral palsy (CP) in an Australian context by a newly established NSW rater network., Methods: A prospective longitudinal cross-sectional study was conducted. The GMA was blind-rated from conventional video by two independent certified raters, blinded to medical history. A third rater resolved disagreements. High-risk population screening for CP using the GMA during the fidgety period (12-20 weeks) was carried out in four neonatal intensive care units and one CP service over a 30-month period (2012-2013). Participants were 259 high-risk infants. Sensitivity and specificity values were calculated with true positives defined as a confirmed diagnosis of CP from a medical doctor., Results: Of the 259 infants assessed, 1-year follow-up data were available for 187. Of these, n = 48 had absent fidgety (high risk for CP), n = 138 had normal fidgety (low risk for CP), and n = 1 had abnormal fidgety (high risk for a neurological disorder). Of the 48 with absent fidgety movements, 39 had received a diagnosis of CP by 18 months and another 6 had an abnormal outcome. Of the n = 138 normal fidgety cases, n = 99 cases had a normal outcome, n = 38 had an abnormal outcome but not CP, and n = 1 had CP. For detecting CP, we had a sensitivity of 98% and specificity of 94%., Conclusion: GMA was feasible in an Australian context and accurately identified CP with a sensitivity and specificity comparable with European standards and published neuroimaging data., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Group 2 innate lymphoid cells (ILC2) are important in effector functions for eliciting allergic inflammation, parasite defense, epithelial repair, and lipid homeostasis. ILC2 lack rearranged Ag-specific receptors, and although many soluble factors such as cytokines and lipid mediators can influence ILC2, direct interaction of these cells with the microenvironment and other cells has been less explored. Natural cytotoxicity receptors are expressed by subsets of group 1 ILC and group 3 ILC and thought to be important for their effector function, but they have not been shown to be expressed by ILC2. Therefore, we sought to investigate the expression and functional properties of the natural cytotoxicity receptor NKp30 on human ILC2. A subset of ex vivo and cultured ILC2 express NKp30 that upon interaction with its cognate activatory ligand B7-H6 induces rapid production of type 2 cytokines. This interaction can be blocked by NKp30 blocking Ab and an inhibitory ligand, galectin-3. Higher expression of B7-H6 was observed in lesional skin biopsies of patients with atopic dermatitis, and incubation of keratinocytes with proinflammatory and type 2 cytokines upregulated B7-H6, leading to increased ILC2 cytokine production. NKp30-B7-H6 interaction is a novel cell contact mechanism that mediates activation of ILC2 and identifies a potential target for the development of novel therapeutics for atopic dermatitis and other atopic diseases., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Alcohol consumption is a potential risk factor for being overweight. We aimed to investigate the effects of an alcohol priming dose and an alcohol-related environment on snacking behaviour. One hundred and fourteen social drinkers completed one of four experimental sessions either receiving a priming dose of alcohol (.6 g/kg) or soft drink in a bar-lab or a sterile lab. Participants provided ratings of appetite, snack urge, and alcohol urge before and after consuming their drinks. Participants completed an ad libitum snack taste test of savoury and sweet, healthy and unhealthy foods before completing the self-reports a final time. Appetite and snack urge increased more following alcohol consumption, and decreased to a lesser extent following the taste test relative to the soft drink. Total calories (including drink calories) consumed were significantly higher in the alcohol groups. There was a marginal effect of environment; those in the bar-lab consumed a higher proportion of unhealthy foods. These effects were more pronounced in those who were disinhibited. While alcohol may not increase food consumption per se, alcohol may acutely disrupt appetite signals, perhaps via processes of reward and inhibitory control, resulting in overall greater calorie intake. Individuals who are generally disinhibited may be more vulnerable to the effects of alcohol and drinking environments on eating behaviour., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: This literature review was designed to examine the role of the arts in medical education. It is distinctive from previous literature reviews in that it focuses specifically on what medical education as a discipline can learn from the arts and does not seek to measure the effectiveness of arts-based educational interventions in students or clinicians., Methods: A literature search using the terms 'educat*' or 'medic*' and phrases such as 'arts', 'therapy', 'medicine', 'arts therapy', 'professional artistry' and 'nursing/doctoral education' was conducted. The 60 items identified were filtered for relevance. Key data were extracted from the remaining items and subjected to a literature analysis to identify important or recurring themes., Results: A total of 39 pieces of literature were included in the study. Collectively, these outlined four main areas in which the use of the arts impacts upon medical education. These refer to using the arts: (i) as a tool for professional development; (ii) to develop pedagogy; (iii) to critique the prevailing approach of medical education, and (iv) to view practice as a succession of performances., Conclusions: The effectiveness of the arts cannot be measured by yardsticks that have been set for judging technical proficiency or short-term impact. The possible outcomes of embracing the arts in medical education include an enriched view of lifelong learning and professional development, the potential to critique prevailing approaches to medical practice, and the revisualisation of medicine as a succession of performances. These open up the broader social aspects of medical practice to scrutiny and offer new and distinctive ways of exploring professional knowledge and identity., (© 2015 John Wiley & Sons Ltd.)

Conjunctival lymphoma is well documented in the medical literature, but veterinary reports are few. We report five cases of canine lymphoma, and three of feline in which the presenting sign was conjunctival involvement. All animals were in apparently good health at the time of presentation, and attended the referring clinic because of conjunctival disease. One dog showed generalized lymphadenopathy at presentation, although the ocular lesion was the reason for consultation, but all other patients were well with no detectable disease beyond the eye. All cats were presented for their ocular disease. All dogs were confirmed to have T-cell tumors, although the histological appearance of these was variable. In contrast, all cats had B-cell tumors. Referring clinicians and owners were contacted for follow-up information. Three dogs had been euthanased within 6 months of diagnosis for deterioration of general health. The remaining two were alive and showed no signs of systemic disease. Two cats had good survival following diagnosis, the other died of lesions that may not be related., (© 2013 American College of Veterinary Ophthalmologists.)

Despite the development of high-titer bioprocesses capable of producing >10 g L(-1) of recombinant monoclonal antibody (MAb), some so called "difficult-to-express" (DTE) MAbs only reach much lower process titers. For widely utilized "platform" processes the only discrete variable is the protein coding sequence of the recombinant product. However, there has been little systematic study to identify the sequence parameters that affect expression. This information is vital, as it would allow us to rationally design genetic sequence and engineering strategies for optimal bioprocessing. We have therefore developed a new computational tool that enables prediction of MAb titer in Chinese hamster ovary (CHO) cells based on the recombinant coding sequence of the expressed MAb. Model construction utilized a panel of MAbs, which following a 10-day fed-batch transient production process varied in titer 5.6-fold, allowing analysis of the sequence features that impact expression over a range of high and low MAb productivity. The model identified 18 light chain (LC)-specific sequence features within complementarity determining region 3 (CDR3) capable of predicting MAb titer with a root mean square error of 0.585 relative expression units. Furthermore, we identify that CDR3 variation influences the rate of LC-HC dimerization during MAb synthesis, which could be exploited to improve the production of DTE MAb variants via increasing the transfected LC:HC gene ratio. Taken together these data suggest that engineering intervention strategies to improve the expression of DTE recombinant products can be rationally implemented based on an identification of the sequence motifs that render a recombinant product DTE., (© 2013 American Institute of Chemical Engineers.)

Genital herpes simplex virus (HSV) is a sexually transmitted infection that can be transmitted from mother to child in utero, perinatally, or postnatally. Cutaneous infection with HSV commonly presents as vesicles affecting the skin, eyes, or mouth. In our case, we report a well child with cutaneous hypopigmented patches at birth that preceded typical blistering., (© 2012 Wiley Periodicals, Inc.)

Objectives:   To evaluate the success rate of various surgical techniques for the management of lower eyelid entropion in cats., Design:   Retrospective study. Animals studied  One hundred and twenty-four cats with surgical correction of lower eyelid entropion of 200 eyes over a 13 year period., Methods:   Records of 124 cats were reviewed for signalment, type of entropion, surgical procedure performed and post-operative result., Results:   Combinations of the Hotz-Celsus (HC), lateral canthal closure and full thickness wedge resection techniques were used to treat 64 bilateral and 60 unilateral cases of lower lid entropion. Twenty-three cats were under a year of age, 52 cats were aged between 2 and 8 years and 49 were over 8 years old. The overall success rate for a single surgical procedure (which may consist of multiple techniques) to correct lower eyelid entropion was 96.0% per eye. The remaining 4.0% had the entropion resolved with a second surgery. A combined HC and lateral canthal closure had a 99.21% success rate of resolving lower lid entropion. Geriatric cats were the most likely age group to develop corneal sequestra; 37% of cats in this group presented with entropion and corneal sequestra concurrently. Seventeen percent of cats that presented with unilateral entropion and did not have prophylactic surgery on the fellow eye went on to develop entropion in the fellow eye., Conclusions:   A combined HC and lateral canthal closure was the most effective surgical technique in managing lower eyelid entropion of cats in our study. Prophylactic lateral canthal closure in the unaffected eye is recommended., (© 2011 American College of Veterinary Ophthalmologists.)

Objectives: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies. The eczema pathway focuses on defining the competences to improve the equity of care received by children with eczema., Method: The eczema pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including paediatricians, allergists, dermatologists, specialist nurses, dietician, patients' representatives and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. It was also reviewed by a wide range of stakeholders., Results: The results are presented in three sections: the evidence review, mapping and the core knowledge document. The various entry points to the ideal pathway of care are defined from self-care through to follow-up. There is considerable emphasis on good skin care and when allergy problems should be dealt with. The pathway algorithm and associated competences can be downloaded from http://www.rcpch.ac.uk/allergy/eczema., Conclusions: Effective eczema management is holistic and encompasses an assessment of severity and impact on quality of life, treatment of the inflamed epidermal skin barrier, recognition and treatment of infection and assessment and management of environmental and allergy triggers. Patient and family education which seeks to maximise understanding and concordance with treatment is also important in all children with eczema.

Objective: To estimate mean Schirmer tear test (STT) and intraocular pressure (IOP) values in healthy koalas both conscious and anesthetized., Methods: Data were gathered from koalas in Victoria, Australia. Conscious examinations were performed on captive koalas. Free-ranging (wild) koalas were examined under anesthesia. Anesthesia was induced using alfaxalone, and animals were maintained on oxygen and isoflurane if required. All animals were healthy and had no surface ocular pathology detectable during slit lamp biomicroscopy. STT I tests were performed using commercial STT test strips placed in the lower fornix for 1 min. IOP was measured using an applanation tonometer after topical anesthesia. The higher value of the two eyes for both STT and IOP was analyzed. STT was measured in 53 koalas (34 conscious, 19 anesthetized) and IOP was measured in 43 koalas (30 conscious, 13 anesthetized). A two-sample t-test was used to compare means. A P-value <0.05 was regarded as significant. Mean ± SD is presented., Results: The mean higher STT in conscious koalas was 10.3 ± 3.6 mm wetting/min and in anesthetized koalas it decreased to 3.8 ± 4.0 mm wetting/min (P < 0.0001). The mean higher IOP in conscious koalas was 15.3 ± 5.1 mmHg, and in anesthetized koalas it was 13.8 ± 3.4 mmHg (P = 0.32). There was no effect of sex on either STT or IOP., Conclusions: The mean and SD of STT and IOP values for koalas both conscious and anesthetized were reported. The mean STT was significantly reduced by alfaxalone anesthesia., (© 2011 American College of Veterinary Ophthalmologists.)

A case of a traumatic scleral rupture with uveal herniation in a dog was treated with an autogenous fascia lata graft. Placement of the graft resolved the uveal prolapse and resulted in return of strength and a more normal structure. Fascia lata appears to be an effective scaffolding graft for the repair of scleral defects. It is cheap, easily harvested and large grafts may be obtained. Healing was rapid and the end result was a cosmetic, comfortable, fully functional eye., (© 2011 American College of Veterinary Ophthalmologists.)

A 2-year-old Jack Russell Terrier was presented for treatment of a worsening corneal ulcer and keratomalacia following removal of a vegetative foreign body. The keratomalacia responded to topical gentamicin therapy; however, the eye became suddenly painful and at examination two areas of increased opacity had developed. Fungal keratitis was demonstrated by corneal scrape showing branching, septate fungal hyphae. Treatment with 1% voriconazole was effective in resolving the keratomycosis.

A large 1.29 x 10(11) antibody fragment library, based upon variable (V) genes isolated from human B-cells from 160 donors has been constructed and its performance measured against a panel of 28 different clinically relevant antigens. Over 5000 different target-specific antibodies were isolated to the 28 antigens with 3340 identified as modulating the biological function (e.g. antagonism, agonism) of the target antigen. This represents an average of approximately 120 different functionally active antibodies per target. Analysis of a sample of >800 antibodies from the unselected library indicates V gene usage is representative of the human immune system with no strong bias towards any particular V(H)-V(L) pairing. Germline diversity is broad with 45/49 functional V(H) germlines and 28/30 V(lambda) and 30/35 V(kappa) light-chain germlines represented in the sample. The number of functional V(H) germlines and V(kappa) light-chain germlines present is increased to 48/49 and 31/35, respectively, when selected V gene usage is included in the analysis. However, following selection on the antigen panel, V(H)1-V(lambda)1 germline family pairings are preferentially enriched and represent a remarkable 25% of the antigen-specific selected repertoire.

Background/objectives: To evaluate a peer modelling, rewards and pedometer-feedback intervention designed to increase children's physical activity and which uses the same behaviour-change principles underlying the Food Dude Healthy Eating Programme., Subjects/methods: The study was conducted in two primary schools in Wales. Participants were 47 children (21 boys, 26 girls) from the experimental school and 53 children (29 boys, 24 girls) from a matched control school, aged 9-11 years. Children in the experimental school took part in the intervention; over 8 days they were introduced to fictional role models (the Fit n' Fun Dudes) via visual and audio intervention materials and received small rewards when their daily pedometer step counts increased by 1500 steps per day relative to their baselines. Pedometer measures were taken from children in both schools at baseline, intervention (baseline 2 for the control school) and 12-week follow-up., Results: Among experimental girls, steps per day were significantly higher during the intervention (14 686+/-2540) and at follow-up (13 737+/-3288) compared to baseline (10 864+/-2481, P<0.001) and control girls (P<0.005). Experimental boys showed significantly higher daily steps during the intervention compared to baseline (16 237+/-4204 cf. 13 452+/-3258, P<0.001) and control boys (P<0.005). There were no significant differences between activity levels of experimental and control boys at follow-up., Conclusions: The intervention resulted in substantial increases in children's physical activity, which was well maintained over a 12-week period in girls.

Primary lipid disorders causing fasting triglyceridaemia have been documented infrequently in Burmese cats. Due to the known increased risk of diabetes mellitus and sporadic reports of lipid aqueous in this breed, the aim of this study was to determine whether healthy Burmese cats displayed a more pronounced pre- or post-prandial triglyceridaemia compared to other cats. Serum triglyceride (TG) concentrations were determined at baseline and variably at 2, 4 and 6h after ingestion of a high-fat meal (ie, an oral fat tolerance test) in a representative sample of Burmese and non-Burmese cats. The median 4 and 6h serum TG concentrations were significantly higher in Burmese cats (4h - 2.8mmol/l; 6h - 8.2mmol/l) than in other pedigree and domestic crossbred cats (4h - 1.5mmol/l; 6h - 1.0mmol/l). The non-Burmese group had post-prandial TG concentrations ranging from 0.6 to 3.9mmol/l. Seven Burmese cats had post-prandial TG concentrations between 6.6 and 19.0mmol/l, five had concentrations between 4.2 and 4.7mmol/l, while the remaining 15 had post-prandial concentrations between 0.5 and 2.8mmol/l. None of these Burmese cats had fasting triglyceridaemia. Most Burmese cats with a 4 h TG > 6.0 mmol/l had elevated fasting very low density lipoprotein (VLDL) concentrations. This study demonstrates that a proportion of Burmese cats in Australia have delayed TG clearance compared to other cats. The potential repercussions of this observation with reference to lipid aqueous, pancreatitis and diabetes mellitus in Burmese cats are discussed.

Aims: Excessive methylation may be a precipitating factor for Parkinson's disease (PD) since S-adenosylmethionine (SAM), the endogenous methyl donor, induces PD-like changes when injected into the rat brain. The hydrolysis of the methyl ester bond of the methylated proteins produces methanol. Since methanol is oxidized into formaldehyde, and formaldehyde into formic acid in the body, we investigated the effects of SAM on the production of methanol, formaldehyde and formic acid in rat brain striatal homogenates and the toxicity of these products in PC12 cells., Main Methods: Radio-enzymatic and colorimetric assays, cell viability, Western blot., Key Findings: SAM increased the formation of methanol, formaldehyde and formic acid in a concentration and time-dependent manner. Concentrations of [3H-methyl]-SAM at 0.17, 0.33, 0.67 and 1.34 nM produced 3.8, 8.0, 18.3 and 34.4 fmol/mg protein/h of [3H] methanol in rat striatal homogenates, respectively. SAM also significantly generated formaldehyde and formic acid in striatal homogenates. Formaldehyde was the most toxic metabolite to differentiated PC12 pheochromocytoma cells in cell culture studies, indicating that formaldehyde formed endogenously may contribute to neuronal damage in excessive methylation conditions. Subtoxic concentration of formaldehyde decreased the expression of tyrosine hydroxylase, the limiting factor in dopamine synthesis. Formaldehyde was more toxic to catecholaminergic PC12 cells than C6 glioma cells, indicating that neurons are more vulnerable to formaldehyde than glia cells., Significance: We suggest that excessive carboxylmethylation of proteins might be involved in the SAM-induced PD-like changes and in the aging process via the toxic effects of formaldehyde.

Objective: To evaluate a peer-modelling and rewards-based intervention designed to increase children's fruit and vegetable consumption., Design: Over a 5-month period, children in an experimental and a control school were presented with fruit and vegetables at lunchtime. Children aged 5-7 y also received fruit at snacktime (mid-morning). The intervention was implemented in the experimental school and levels of fruit and vegetable consumption were measured at baseline, intervention and at 4-month follow-up., Setting: Two inner-city London primary schools., Subjects: In total, 749 children aged 5-11 y., Intervention: Over 16 days children watched video adventures featuring heroic peers (the Food Dudes) who enjoy eating fruit and vegetables, and received small rewards for eating these foods themselves. After 16 days there were no videos and the rewards became more intermittent., Main Outcome Measures: Consumption was measured (i) at lunchtime using a five-point observation scale; (ii) at snacktime using a weighed measure; (iii) at home using parental recall., Results: Compared to the control school, lunchtime consumption in the experimental school was substantially higher at intervention and follow-up than baseline (P<0.001), while snacktime consumption was higher at intervention than baseline (P<0.001). The lunchtime data showed particularly large increases among those who initially ate very little. There were also significant increases in fruit and vegetable consumption at home (P<0.05)., Conclusions: The intervention was effective in bringing about substantial increases in children's consumption of fruit and vegetables.

Progressive osseous heteroplasia (OMIM 166350) is a rare autosomal dominant condition that presents in childhood as dermal ossification and may progress deeper to involve subcutaneous fat and connective tissue. Recently, paternally inherited inactivating mutations in the GNAS1 gene on chromosome 20q13 have been implicated in the pathogenesis, although sporadic cases have also been reported. We report a 9-year-old British Chinese girl with progressive osseous heteroplasia resulting from a de novo missense mutation (W281R) in the GNAS1 gene. She is of small stature (0.4th centile) and started to develop skin lesions at the age of 9 months. These have been confirmed histologically as osteoma cutis. She is of normal intelligence and development and has no dysmorphic features. The GNAS1 gene exhibits imprinting and maternally inherited mutations have previously been shown to result in Albright's hereditary osteodystrophy (OMIM 103580) with pseudohypothyroidism type 1a, whereas paternally inherited mutations result in progressive osseous heteroplasia or the Albright's hereditary osteodystrophy phenotype with pseudopseudohypothyroidism (OMIM 300800). With only nine mutations of the GNAS1 gene reported so far in progressive osseous heteroplasia, this new mutation helps to extend further the genotype-phenotype correlation.

Many authors have reported that the claustrum, which comprises the insular claustrum and the endopiriform nucleus, is missing from the monotreme forebrain. We used Nissl and myelin staining in conjunction with enzyme histochemistry for acetylcholinesterase and immunohistochemistry for parvalbumin, calbindin, calretinin and tyrosine hydroxylase to examine the brains of two monotremes, the short-beaked echidna (Tachyglossus aculeatus) and the platypus (Ornithorhynchus anatinus). We found that although the insular claustrum is a small structure in the echidna brain, it is nevertheless clearly present as loosely clustered neurons embedded in the white matter ventrolateral to the putamen and deep to the piriform and entorhinal cortices. Neurons in this region share the chemical features of the adjacent cortex (presence of a similar proportion of parvalbumin immunoreactive neurons and minimal activity for acetylcholinesterase and tyrosine hydroxylase), unlike the adjacent putamen and ventral pallidum. A putative endopiriform nucleus can be identified in the interior of the piriform lobe of the echidna as calretinin immunoreactive neurons embedded within the white matter. The situation is much less clear in the platypus, but our data suggest that there may be an insular claustrum deep to frontal cortex, separated from layer VI by only a thin layer of white matter. We could not identify an endopiriform nucleus in our platypus material. Our findings indicate that presence of the claustrum cannot be considered a feature confined to therian mammals and lend weight to arguments that this structure was present in the ancestral mammalian brain.

A 6-month-old Rhodesian ridgeback-cross, a 6-year-old Chihuahua and a 12-month-old Australian cattle dog were presented to the authors with a history of colliding with obstacles in daylight. Ophthalmic examination was normal and all three dogs successfully negotiated obstacle courses in dim light. In daylight the dogs became suddenly blind and repeatedly collided with obstacles. Elecroretinography (ERG) revealed no retinal activity to high frequency (30 Hz), bright intensity blue light retinal stimulation by any dog, confirming cone dysfunction. Achromatopsia has previously been recorded in Alaskan malamutes and miniature poodles. This clinical case series illustrates the characteristic behavioral presentation and the electroretinographic findings of severe day-blindness and demonstrates that this condition may exist in other breeds of dogs.

Cutaneous sarcoidosis is rare in children. We report a case of a 5-year-old Bangladeshi girl who presented with fever, a papular eruption on the lower limbs and trunk, malaise, anorexia and weight loss. There was multisystem involvement with marked hepatosplenomegaly, generalized lymphadenopathy, parotid fullness and chronic uveitis. Pulmonary infiltrates were seen on the chest X-ray. Histology of a skin biopsy showed naked noncaseating granulomata and PCR for Mycobacterium tuberculosis was negative. A clinical diagnosis of sarcoidosis was made. The patient was treated with oral prednisolone (2 mg/kg per day). An excellent clinical response with resolution of the rash and improvement of extracutaneous signs was noted within 3 months and she remains well on low-dose prednisolone on alternate days. We discuss the presentation and management of sarcoidosis in children, and highlight the potential difficulty in differentiating this from disseminated tuberculosis.

A 16-month-old, male, neuter Dwarf Lop rabbit presented with exophthalmos of the right eye of 3 weeks duration. Under sedation an ultrasound of the right eye was performed and showed an orbital hypo-echoic area posterior and ventrolateral to the right globe, which was presumed to be a cyst. Fine needle aspirate removed 5.5 mLs of straw-colored fluid from the cyst, which allowed the globe to return to its normal position. Two months later the rabbit re-presented with exophthalmos of the right eye. Exploratory surgery was performed and a large cystic structure was removed from the ventro-lateral conjunctival fornix. Histology confirmed the cyst to be a coenurus of Taenia serialis.

Objective: To evaluate a higher total energy protocol for diode laser transscleral cyclophotocoagulation (TSCP) for the treatment of primary glaucoma in dogs., Procedures: Diode laser TSCP was performed on 24 eyes of 18 dogs (six dogs were treated bilaterally). A glaucoma probe with a spot size of 600 microns was applied in 25 sites 3-4 mm posterior to the limbus for dogs. A power of 1000 milliwatts (mW) for a duration of 5000 milliseconds (ms) to deliver an average 125 J of energy per eye, which is higher energy delivery than previously reported for the diode laser for the treatment of canine glaucoma. Anterior chamber needle paracentesis was performed using a 30-gauge needle until intraocular pressure (IOP) was measured to be less than 15 mmHg by applanation tonometry. Subconjunctival corticosteroids were administered in all cases and a temporary tarsorrhaphy was applied in 13 of the 24 treated eyes. Postoperative topical and systemic corticosteroids, and carbonic anhydrase inhibitors were administered as required to maintain an IOP of less than 25 mmHg. Intraocular pressure was measured at approximately 3 h postoperatively then at 1, 2, 3, 7, 14, 28, 60, 120, and 180 days. Adequate control of IOP was considered to be less than 25 mmHg on re-examination., Results: Intraocular pressure was successfully maintained within the normal range in 22/24 eyes (92%). Three eyes required a second diode laser treatment within the first week postoperatively. Two eyes developed recurrence of glaucoma at 8 and 32 weeks postoperatively. Follow-up ranged from 8 to 21 months. Fourteen eyes were assessed by clinical examination and history to be potentially visual. Of these, seven eyes (50%) regained useful visual function. Mean IOP at 6 months was 11.0 +/- 7.6 mmHg and at 12 months was 11.0 +/- 8 mmHg. Postoperative complications included cataracts (six cases), corneal ulceration (three cases), and keratitis (three cases). Of 13 cases that were treated postoperatively with a temporary tarsorrhaphy, only one case (8%) developed corneal disease. Of the remaining 11 cases that were not treated with a temporary tarsorrhaphy, there were three cases of corneal ulceration and two cases of vascular keratitis (45% incidence of corneal disease). This was found to be statistically significant (P < 0.05). Postoperative complications of hyphema and phthisis bulbi were not seen in this series., Conclusion: Low energy, higher power laser cyclophotocoagulation was effective in the treatment of canine primary glaucoma, with 50% of potentially visual eyes regaining vision, but may cause an increased incidence of secondary cataracts.

A 3-year-old Paint gelding was presented for sudden onset of cataract affecting the right eye. Ophthalmic examination revealed subtle to mild microphthalmia and a mature cataract affecting the right globe. The right eye was treated with an antibiotic-corticosteroid ophthalmic ointment and phacofragmentation was recommended. On re-examination 5 months later, resorption of the cortex of the right lens and a morgagnian cataract were evident. The nucleus was positioned ventronasally in the lens capsule. The right eye had light perception, and a menace response was present. Examination of the right fundus via binocular indirect ophthalmoscopy was not possible. Ophthalmic ultrasonography revealed that the right globe was 4 mm shorter in axial length when compared with the left globe. There was a marked reduction in the size of the right lens vs. the left lens, and the presence of a moderate amount of hyperechoic debris was identified within the vitreal compartment of the right globe. Phacofragmentation, irrigation and aspiration of the morgagnian cataract and an anterior vitrectomy were performed. On postoperative examination, the eye was comfortable and a menace response was present. The horse regained useful vision and continues to have a comfortable, visual eye 7 months postoperatively.

Recently we have demonstrated that a disease-specific subpopulation of CD4+ T cells isolated from skin lesions of chronic plaque psoriasis produces interferon-gamma in response to group A streptococcal (GAS) antigens. To determine if these T cells recognize M or non-M protein, extracts from cell wall of type M6 GAS (M6W) and its isogenic M gene deletion mutant (M-W), M6 membrane extract (M6M) and recombinant M6 protein (rM6) were used to stimulate GAS-reactive T-cell lines from nine patients with chronic plaque psoriasis. T-cell lines were incubated with or without streptococcal extracts for 18 h in the presence of a transport inhibitor, stained for surface CD4 and intracellular cytokine expression, and analysed by flow cytometry. Variable numbers (0.2-34%) of CD4+ T cells produced interferon-gamma, in all but one of the T-cell lines tested, in response to M6W, M-W and M6M extracts. No significant difference between the response to M6W and M-W extracts was detected. In addition, rM6 protein failed to increase CD4+/interferon-gamma+ T-cell numbers in seven of nine T-cell lines compared to medium alone. For the group, there was a highly significant correlation between the responses to the three extracts (M6W vs M-W, P = 0.0005; M6W vs M6M, P = 0.0003; M-W vs M6M, P = 0.0001). Low or minimal numbers of interleukin-4- and interleukin-10-producing CD4+ T cells were occasionally induced. These findings suggest that a subpopulation of CD4+ T cells isolated from skin lesions of chronic plaque psoriasis patients produces interferon-gamma in response to non-M protein(s) present on the cell wall and membrane of GAS.

We describe a 42-year-old woman who developed lichen myxoedematosus. Twenty years after the onset of the disease she became breathless and hypertensive, and an echocardiogram showed a mass on the mitral valve, which was thought to be a mucin deposit. Her hypertension was resistant to treatment with combination antihypertensives. To our knowledge, this is the first report to link lichen myxoedematosus with a valvular mucinous mass. This case also demonstrates the slow clinical progression of the disease over 20 years.