Bacterial endometritis-induced changes in the endometrial proteome in mares: Potential uterine biomarker for bacterial endometritis.

Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics.

The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population.

INTRODUCTION: Myasthenia gravis (MG) is a rare neuromuscular disorder marked by a variable combination of weakness of eye, bulbar, respiratory, axial, and limb muscles. This study compared the experience of people with MG regarding breathing, fatigue, sleep, pain/discomfort, mental health, and usual activities with the general population. METHODS: The MyRealWorld-MG digital, multinational study enrolled patients with MG and collected demographics, PROMIS-Dyspnea, PROMIS-Sleep Disturbance, FACIT-Fatigue, EQ-5D-5L, Health Utilities Index (HUI-3), Hospital Anxiety and Depression Scale (HADS), MG-Activities of Daily Living (MG-ADL), and MG-Quality-of-Life (MG-QoL-15r). Comparisons with the general population were based on PROMIS population norms, published literature, or on data from a digital, multinational, observational study which enrolled a representative sample of the general population (POPUP). RESULTS: In MyRealWorld-MG (N = 2074), patients experienced higher intensity, frequency, and duration of PROMIS shortness of breath than a US population (p < 0.0001). Patients with MG had higher PROMIS-Sleep Disturbance scores than POPUP (53.7 vs 50.0, p < 0.0001), and 54.9% of patients had clinically severe FACIT-Fatigue scores vs 6.8% in POPUP (p < 0.0001). Among patients with MG, 69.6% and 18.5% had moderate-to-severe HADS-Anxiety and HADS-Depression compared to 20.3% and 6.9% in POPUP (p < 0.001). Statistically significant and strong associations were found between fatigue, sleep, dyspnea, usual activities, and emotions. All outcomes worsened with more severe disease. CONCLUSION: A considerable burden was observed in this comparison of breathing, sleep, fatigue, mental health, and usual activities between patients with MG and the general population, using data from two international studies and published population norms. Even mildly affected patients had significantly worse outcomes than the general population.

People Diagnosed with Myasthenia Gravis have Lower health-related quality of life and Need More Medical and Caregiver Help in Comparison to the General Population: Analysis of Two Observational Studies.

INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease causing extreme muscular fatigue, triggering problems with vision, swallowing, speech, mobility, dexterity, and breathing. This analysis intended to estimate the health-related quality-of-life impact, the medical burden, and the need for caregiver help of people diagnosed with MG. METHODS: MyRealWorld-MG (MRW) is an observational study among adults diagnosed with MG in 9 countries. The General Population Norms (POPUP) observational study enrolled representative members of the general population in 8 countries. In both digital studies, respondents entered personal characteristics and provided data on medical conditions, EQ-5D-5L, HUI3, MG-Activities of Daily Living (MG-ADL), sick leave, caregiver help, and medical care utilization. RESULTS: In MRW (n = 1859), 58.4% of respondents had moderate-to-severe MG. Average utility values were lower in MRW versus POPUP (0.739 vs. 0.843 for EQ-5D-5L; 0.493 vs. 0.746 for HUI3), and declined with more severe disease (0.872, 0.707, 0.511 EQ-5D-5L utilities and 0.695, 0.443, 0.168 HUI3 utilities for mild, moderate, and severe MG, respectively). Taking sick leave in the past month was 2.6 times more frequent among people diagnosed with MG compared to the general population (34.4% vs. 13.2%) and four times more people diagnosed with MG reported needing help from a caregiver (34.8% vs. 8.3%). Use of medical care was twice as likely in MRW in comparison with POPUP (51.9% vs. 24.6%). CONCLUSION: This direct comparison of people diagnosed with MG and the general population using two large international studies revealed significant negative impact of MG. Results were consistent across all outcomes, in all countries.

Evaluation of testicular echotexture with Ecotext as a diagnostic method of testicular dysfunction in stallions.

This study aimed to assess if Ecotext, a new software for evaluation of testicular echotexture, is a good method for diagnosis of stallions with testicular dysfunction (TD). Relationships between Ecotext parameters and sperm motility and production, testicular volume, and testicular blood flow were also studied. Ecotext provides a total of six echotexture parameters: Ecotext 1 (black pixels), 2 (white pixels) and 3 (grey pixels), and another 3 parameters related to hypoechogenic areas: Ecotext tubular density (ETD), Ecotext tubular diameter (ETd), and Ecotext tubular area (ETA). Stallions (n = 33) were assessed using proven diagnostic techniques (spermiogram, B-mode and Pulse Doppler ultrasound), and subsequent analysis with Ecotext. Animals were classified as "control stallions" (n:21, acceptable semen quality), and "stallions with TD" (n:12, poor semen quality (TM < 60%, PM < 45% and total nº of sperm with PM < 2000 × 106 spz), that were subdivided into "induced TD group" (immunized, anti-GnRH vaccine) and "acquired TD group". The acquired TD group showed differences in all Ecotext parameters in relation to controls (Ecotext 1:0.11 ± 0.17 vs 2.82 ± 2.52, Ecotext 2:1584.0 ± 575.8 vs 388 ± 368.2, Ecotext 3:134.2 ± 9.26; ETA: 2.14 ± 0.59 vs 5.40 ± 1.90; ETd: 65.66 ± 6.27 vs 86.93 ± 10.65 and ETD: 92.35 ± 11.24 vs 132.10 ± 16.35, p ≤ 0.001). Results suggest acquired TD stallions were suffering testicular degeneration with loss of architecture and function as all Ecotext parameters were altered in relation to controls. Induced TD horses only showed a reduction in ETD (116.2 ± 8.59 vs 132.10 ± 16.35, p ≤ 0.001), despite all sperm parameters being worse. These findings suggested immunized stallions probably only experience an acute loss of testicular functionality and parenchyma architecture is likely not affected since differences in Ecotext parameters with control stallions were not detected. ETD was the best parameter to identify animals with TD (AUC: 0.84, optimal cut-off value of 124.3 seminiferous tubules/cm2). Correlations were found between ETD and Doppler indices (PI: 0.60; RI: 0.47 p ≤ 0.001), total testicular volume (r: 0.48; p ≤ 0.05) and sperm motility (TM:0.51; and PM:0.54; p ≤ 0.001) and production (r:0.51; p ≤ 0.001). In summary, Ecotext could identify changes in testicular echotexture of stallions with TD. Results open the possibility for new research focused on establishing the relationship between Ecotext parameters and histomorphometry features in stallion testes.

Network Canvas: Key decisions in the design of an interviewer assisted network data collection software suite.

Self-reported social network analysis studies are often complex and burdensome, both during the interview process itself, and when conducting data management following the interview. Through funding obtained from the National Institute on Drug Abuse (NIDA/NIH), our team developed the Network Canvas suite of software - a set of complementary tools that are designed to simplify the collection and storage of complex social network data, with an emphasis on usability and accessibility across platforms and devices, and guided by the practical needs of researchers. The suite consists of three applications: Architect: an application for researchers to design and export interview protocols; Interviewer: a touch-optimized application for loading and administering interview protocols to study participants; and Server: an application for researchers to manage the interview deployment process and export their data for analysis. Together, they enable researchers with minimal technological expertise to access a complete research workflow, by building their own network interview protocols, deploying these protocols widely within a variety of contexts, and immediately attaining the resulting data from a secure central location. In this paper, we outline the critical decisions taken in developing this suite of tools for the network research community. We also describe the work which guides our decision-making, including prior experiences and key discovery events. We focus on key design choices, taken for theoretical, philosophical, and pragmatic reasons, and outline their strengths and limitations.

IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies.

BACKGROUND: Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents. PATIENTS AND METHODS: Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0. RESULTS: A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab. CONCLUSIONS: IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies.

Assessing professional competence in optometry - a review of the development and validity of the written component of the competency in optometry examination (COE).

BACKGROUND: Credentialing assessment for overseas-educated optometrists seeking registration in Australia and New Zealand is administered by the Optometry Council of Australia and New Zealand. The aim was to review the validation and outcomes of the written components of this exam to demonstrate credentialing meets entry-level competency standards. METHODS: The Competency in Optometry Examination consists of two written and two clinical parts. Part 1 of the written exam comprises multiple choice questions (MCQ) covering basic and clinical science, while Part 2 has 18 short answer questions (SAQ) examining diagnosis and management. Candidates must pass both written components to progress to the clinical exam. Validity was evaluated using Kane's framework for scoring (marking criteria, item analysis), generalization (blueprint), extrapolation (standard setting), and implications (outcome, including pass rates). A competency-based blueprint, the Optometry Australia Entry-level Competency Standards for Optometry 2014, guided question selection with the number of items weighted towards key competencies. A standard setting exercise, last conducted in 2017, was used to determine the minimum standard for both written exams. Item response theory (Rasch) was used to analyse exams, produce reliability metrics, apply consistent standards to the results, calibrate difficulty across exams, and score candidates. RESULTS: Data is reported on 12 administrations of the written examination since 2014. Of the 193 candidates who sat the exam over the study period, 133 (68.9%) passed and moved on to the practical component. Ninety-one (47.2%) passed both the MCQ and SAQ exams on their first attempt. The MCQ exam has displayed consistently high reliability (reliability index range 0.71 to 0.93, average 0.88) across all 12 administrations. Prior to September 2017 the SAQ had a set cutscore of 50%, and the difficulty of the exam was variable. Since the introduction of Rasch analysis to calibrate difficulty across exams, the reliability and power of the SAQ exam has been consistently high (separation index range 0.82 to 0.93, average 0.86). CONCLUSIONS: The findings from collective evidence support the validity of the written components (MCQ and SAQ) of the credentialing of the competency of overseas-educated optometrists in Australia and New Zealand.

Observational study of pre-operative intravenous iron given to anaemic patients before elective cardiac surgery.

Cardiac surgical patients with anaemia experience increased morbidity and mortality. Iron deficiency is the most common cause of pre-operative anaemia in this group. We designed and implemented the Cardiff Pathway, a pre-assessment and treatment pathway to identify cardiac surgical patients with anaemia and iron deficiency. Patients identified with anaemia and/or iron deficiency (Hb < 130 g.l-1 and ferritin < 100 µg.l-1 ) were offered intravenous iron infusion 20 mg.kg-1 pre-operatively. Treatment success was defined as Hb ≥ 130g.l-1 on the day of surgery. We analysed data from 447 patients: 300 (67%) were not anaemic; 75 (17%) were anaemic and treated with intravenous iron; and 72 (16%) were anaemic and not treated. Haemoglobin concentration increased in successfully treated anaemic patients by a mean (95%CI) of 17 (13-21) g.l-1 and they received a median (IQR [range]) of 0 (0-2 [0-15]) units of blood peri-operatively. Transfusion was avoided in 54% of the successfully treated anaemic patients, which was significantly more than the unsuccessfully treated anaemic (22%, p = 0.005) and untreated anaemic (28%, p = 0.018) patients and similar to non-anaemic patients who received a median (IQR [range] of 0 (0-1 [0-16])) units of blood and, 63% avoided transfusion). Mean (95%CI) Hb fell between pre-assessment and surgery in the untreated anaemic (-2 (0 to -4) g.l-1 ) and non-anaemic groups (-2 (-1 to -3) g.l-1 ). Twenty-one (7%) of the non-anaemic group became newly anaemic waiting for surgery. The Cardiff Pathway reliably identified patients with anaemia and iron deficiency. Anaemic patients who had their Hb restored to normal after treatment required less blood peri-operatively and over half of them required no transfusion at all.

The Use Of Dermal Regeneration Templates For Primary Burns Surgery In A UK Regional Burns Centre.

The gold standard of treatment for major burns is early burn excision and autografting. In major burns this is complicated by a lack of donor site availability. Another challenge after burn injury is achieving optimal cosmetic and functional outcomes. Dermal regeneration templates (DRT) are biomatrices that help to address these problems. Within our centre the most commonly used are two-stage Integra® and single-stage Matriderm®. We review the use and outcomes of DRT in primary burns reconstruction within our regional burns centre. All patients undergoing primary burn reconstruction using Integra® (n=59) or Matriderm® (n=35) over a 13-year period were included. Integra® was used in patients with significantly larger burns (20.4% TBSA vs 1.7% TBSA). Comparable levels of graft take were seen in both groups. Major infections were significantly higher in the Integra® group (11/35 compared to 3/59). There was no significant difference in haematoma development, hypertrophic scarring or the need for secondary reconstructive surgery. Burn contractures developed in 15 patients treated with Matriderm® and 21 with Integra®. DRT have been used safely and effectively and have played an increasingly important role in our service over the last 13 years. Integra® is used primarily in large burns with limited donor sites and Matriderm® in smaller burns in cosmetically sensitive areas.

Le traitement de référence des brûlures graves est l'excision précoce et la greffe autologue. Dans ces brûlures graves, ce traitement peut s'avérer difficile par le manque de disponibilité de sites donneurs. De plus, l'obtention de résultats satisfaisants tant sur le plan cosmétique que fonctionnel est un véritable challenge dans les suites de brûlures. Les matrices dermiques (DRT) sont des biomatériaux qui peuvent aider à résoudre ces problèmes. Dans notre centre, les matrices le plus souvent utilisées sont Integra® double couche et Matriderm ®. Nous avons étudié l'utilisation des matrices dermiques et leurs résultats dans la chirurgie primaire des brûlures dans notre centre de traitement des brûlures de province. Tous les patients ayant bénéficié d'une chirurgie primaire pour brûlure par Integra® (n=59) et par Matriderm® (n=35) dans les 13 dernières années ont été inclus. Integra® a été utilisé pour des patients présentant des brûlures significativement plus étendues (20,4% TBSA vs 1,7% TBSA). Le taux de prise des greffes est comparable dans les deux groupes. Les infections sévères sont plus élevées de façon significative dans le groupe traité par Integra® (11/59 contre 3/35). Il n'y a pas de différence significative en ce qui concerne les hématomes, l'évolution hypertrophique des cicatrices ou la nécessité de chirurgie secondaire. Des rétractions cicatricielles sont apparues chez 15 patients traités par Matriderm® et chez 21 patients traités par Integra®. L'utilisation des matrices dermiques nous semble sûre et utile et a été largement développée ces 13 dernières années dans notre centre. Integra® est utilisé en chirurgie primaire pour les brûlures très étendues où les sites donneurs font défaut alors que Matriderm® est utilisé pour les brûlures de petite surface à enjeu fonctionnel et cosmétique.

A comparative in vitro toxicity assessment of electronic vaping product e-liquids and aerosols with tobacco cigarette smoke.

The use of electronic vaping products (EVPs) continues to increase worldwide among adult smokers in parallel with accumulating information on their potential toxicity and relative safety compared to tobacco smoke. At this time, in vitro assessments of many widely available EVPs are limited. In this study, an in vitro battery of established assays was used to examine the cytotoxic (Neutral red uptake), genotoxic (In vitro micronucleus) and mutagenic (Bacterial reverse mutation) responses of two commercial EVPs (blu GO™ disposable and blu PLUS+™ rechargeable) when compared to smoke from a reference cigarette (3R4F). In total, 12 commercial products were tested as e-liquids and as aerosols. In addition, two experimental base liquids containing 1.2% and 2.4% nicotine were also assessed to determine the effect of flavour and nicotine on all three assays. In the bacterial reverse mutation (Ames) and in vitro micronucleus (IVM) assays, exposures to e-liquids and EVP aerosols, with and without nicotine and in a range of flavourings, showed no mutagenic or genotoxic effects compared to tobacco smoke. The neutral red uptake (NRU) assay showed significantly reduced cytotoxicity (P < .05) for whole undiluted EVP aerosols compared to tobacco smoke, which by contrast was markedly cytotoxic even when diluted. The reduced in vitro toxicological responses of the EVPs add to the increasing body of scientific weight-of-evidence supporting the role of high-quality EVPs as a harm reduction tool for adult smokers.

Multiple Sclerosis Performance Test: validation of self-administered neuroperformance modules.

BACKGROUND AND PURPOSE: The purpose was to determine the test-retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self-administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression-based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example. METHODS: Substudy 1 assessed test-retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples. RESULTS: The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician-administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample. CONCLUSIONS: The self-administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting.

Power Doppler can detect the presence of 7-8 day conceptuses prior to flushing in an equine embryo transfer program.

In order to determine whether differences in uterine blood flow between pregnant and non-pregnant mares can be used to predict the presence of the equine embryo prior to flushing in an embryo transfer program, power Doppler ultrasonography was used on a total of 52 mares on days 7 or 8 post-ovulation. Computer analysis of Doppler images was subsequently performed using ImageJ v1.48 software. Vascular perfusion of the endometrium was analyzed using spot meter techniques, measuring mean pixel intensity and area of blood flow. Mares with positive flushings presented a higher uterine blood flow area (one embryo: 54.01 ± 2.27 mm2 or two embryos: 61.01 ± 6.73 mm2) prior to embryo recovery compared to barren mares (21.77 ± 2.22 mm2) (p≤0.05). However, significant differences in vascular perfusion were not detected between single or twin pregnancies. Blood flow area appears to be a good predictor for differentiation between pregnant and non-pregnant mares with an AUC: 0.869; p≤0.001 and an optimal cut-off value of 37.21 mm2. Both the mare's age and day of embryo recovery caused effects on uterine vascular perfusion. According to Youden's J statistics the uterine blood flow area of young pregnant mares was greater than 25.4 mm2 on day 7 (with a sensitivity of 75% and a specificity of 87.5%) and greater than 21.02 mm2 on day 8 post-ovulation (with a sensitivity of 93.8% and a specificity of 100%). The uterine blood flow area in adult pregnant mares was greater than 41.4 mm2 on day 7 (with a sensitivity of 80% and a specificity of 85.5%) and greater than 35.55 mm2 on day 8 after ovulation (with a sensitivity of 97.2% and a specificity of 85.7%). Evaluation on day 8 is therefore considered to be more reliable. Older and middle aged pregnant mares (5-18 years old) had increased uterine vascularization compared to young pregnant mares (2-5 years old) (p≤0.001). Conversely, older barren mares showed higher endometrial vascularity (35.06 ± 2.56 mm2) than young (17.21 ± 1.26 mm2) and middle aged non-pregnant mares (23.84 ± 1.50 mm2) (p≤0.05). We hypothesized that the higher blood flow area seen in older barren mares may be a consequence of a subclinical endometritis due to repeated flushing for embryo recovery. The results of the present study indicate that power Doppler ultrasound combined with computer assisted analysis of images are reliable techniques to detect early pregnancy prior to embryo recovery.

Changing player behaviour in sport during the COVID-19 pandemic: Shake on it?

To prevent the spread of infection during matches and training activities is a major challenge facing all sports returning from the enforced COVID-19 shutdown. During training and matches, rugby league players make contact with others which can result in SARS-CoV-2 virus transmission. While these interactions characterise the appeal of the game, a number of them can be avoided, including shaking hands and conversing after the match. This paper presents a framework underpinned by behavioural science (capability, opportunity, motivation and behaviour model, COM-B) to support stakeholders in helping players adopt new social distance norms and behaviours. This framework helps to ensure the players have the capability, opportunity, and motivation to adopt new COVID-19 risk minimising behaviours, which they will need to commit to 100%.

Outpatient dermatology consultations for oncology patients with acute dermatologic adverse events impact anticancer therapy interruption: a retrospective study.

BACKGROUND: Dermatologic adverse events (dAEs) of anticancer therapies may negatively impact dosing and quality of life. While therapy interruption patterns due to dAEs have been studied in hospitalized cancer patients, similar outcomes in outpatient oncodermatology are lacking. OBJECTIVES: To analyse the therapy interruption patterns, clinico-histopathologic characteristics and management outcomes of outpatient dermatology consultations for acute dAEs attributed to the most frequently interrupted class of oncologic agents. METHODS: We performed a retrospective cohort study of all cancer patients who received a same-day outpatient dermatology consultation for acute dAEs at our institution from 1 January to 30 June 2015. Relevant data were abstracted from electronic medical records, including demographics, oncologic history and explicit recommendations by both the referring clinician and consulting dermatologist on anticancer therapy interruption. Consultations with the most frequently interrupted class of oncologic treatment were characterized according to clinico-histopathologic features, dermatologic management and clinical outcomes. RESULTS: There were 426 same-day outpatient dermatology consultations (median age 59, 60% female, 30% breast cancer), of which 295 (69%) had systemic anticancer therapy administered within 30 days prior. There was weak inter-rater agreement between referring clinicians and consulting dermatologists on interruption of anticancer treatment (n = 150, κ = 0.096; 95% CI -0.02 to 0.21). Seventy-three (25%) consultations involved interruption by the referring clinician, most commonly targeted therapy (24, 33%). Maculopapular rash was commonly observed in 23 consultations with 25 dAEs attributed to targeted agents (48%), and topical corticosteroids were most frequently utilized for management (22, 38%). The majority (83%) of consultations with targeted therapy-induced dAEs responded to dermatologic treatment and 84% resumed oncologic therapy, although three (19%) at a reduced dose. Rash recurred only in two instances (13%). CONCLUSIONS: A high frequency of positive outcomes in the management of targeted therapy-induced dAEs by outpatient consulting dermatologists and low recurrence of skin toxicity suggests impactful reductions in interruption of anticancer therapy.

Altered Schaedler flora mice: A defined microbiota animal model to study the microbiota-gut-brain axis.

Despite considerable attention, the mechanisms by which the microbiota affect brain function and host behaviour via the gut-brain axis remain undefined. Identifying microbe-specific pathways that influence neuronal function and bi-directional communication between the gut microbiota and the host central nervous system is challenging due to the extreme microbial diversity in the gut of conventionally-reared mice. Herein, we describe the use of the altered Schaedler flora (ASF) mouse model as an alternative to conventionally-reared and germ-free animals. Colonized with only 8 bacterial species, use of ASF mice greatly simplifies the examination of microbiota-host interactions. We assessed the extent to which behaviour differed between mice with a limited consortium of bacteria compared with a complex, conventional microbiota. The elevated plus maze and open-field assays were utilized to assess murine behaviour. Histological analysis of ileum and colon was performed to evaluate intestinal morphology, and 16 s rRNA gene taxonomic profiling was performed to determine host-stress induced changes in fecal microbial communities. Behavioural and serum corticosterone differences were observed between ASF and conventionally-reared mice, while no differences were found between the intestinal morphology of these two groups. The stress of the behavioural tests induced significant changes in the ASF fecal microbial community but not in that of the conventionally-reared mice. In contrast to the conventionally-reared mice, the results indicated that the ASF mice displayed a marked anxiogenic-like behaviour. These data indicate that ASF mice represent a unique model to elucidate mechanisms governing microbiota-gut-brain communication affecting behaviour.

Patient and carer experience of blended diet via gastrostomy: a qualitative study.

BACKGROUND: Home enteral feeding is becoming increasingly prevalent within the UK. The use of commercial prescription formula is considered best practice; however, increasingly, patients are choosing to use blended diet via gastrostomy. There is anecdotal evidence suggesting both physical and social benefits, although there are concerns regarding the safety and efficacy of this method of feeding. The present study explores the experiences of patients who are currently using or have used this method of feeding in the past. METHODS: Patients currently using or having previously used blended diet via gastrostomy were identified. Patients and their carers, where applicable, were invited to participate in a semi-structured interview. The data were transcribed and themes were identified. RESULTS: Thematic analysis of the data collected showed that patients had an overall positive experience of blended diet with few or no identified disadvantages. Participants reported improvements in gastrointestinal symptoms, as well as general wellbeing, in addition to the social benefits of their family member being included in family mealtimes. Reference was made to the lack of support for this method of feeding and the desire for blended diet to be offered as an alternative to commercial enteral feed. CONCLUSIONS: This research highlights the benefits of blended diet via gastrostomy as an alternative to commercial formula. More research is needed to develop evidence-based guidelines for patients and the healthcare professionals supporting them.

Correction to: Acceptability of HIV self-sampling kits (TINY vial) among people of black African ethnicity in the UK: a qualitative study.

It has been highlighted that in the original article [1] there is a typesetting mistake in the name of I. Fakoya. This was incorrectly captured as F. Fakoya. This correction article clarifies the correct name of the author.

Acceptability of HIV self-sampling kits (TINY vial) among people of black African ethnicity in the UK: a qualitative study.

BACKGROUND: Increasing routine HIV testing among key populations is a public health imperative, so improving access to acceptable testing options for those in need is a priority. Despite increasing targeted distribution and uptake of HIV self-sampling kits (SSKs) among men who have sex with men in the UK, little is known about why targeted SSK interventions for black African users are not as wide-spread or well-used. This paper addresses this key gap, offering insight into why some groups may be less likely than others to adopt certain types of SSK interventions in particular contexts. These data were collected during the development phase of a larger study to explore the feasibility and acceptability of targeted distribution of SSKs to black African people. METHODS: We undertook 6 focus groups with members of the public who self-identified as black African (n = 48), 6 groups with specialists providing HIV and social services to black African people (n = 53), and interviews with HIV specialist consultants and policy-makers (n = 9). Framework analysis was undertaken, using inductive and deductive analysis to develop and check themes. RESULTS: We found three valuable components of targeted SSK interventions for this population: the use of settings and technologies that increase choice and autonomy; targeted offers of HIV testing that preserve privacy and do not exacerbate HIV stigma; and ensuring that the specific kit being used (in this case, the TINY vial) is perceived as simple and reliable. CONCLUSIONS: This unique and rigorous research offers insights into participants' views on SSK interventions, offering key considerations when targeting this population.. Given the plethora of HIV testing options, our work demonstrates that those commissioning and delivering SSK interventions will need to clarify (for users and providers) how each kit type and intervention design adds value. Most significantly, these findings demonstrate that without a strong locus of control over their own circumstances and personal information, black African people are less likely to feel that they can pursue an HIV test that is safe and secure. Thus, where profound social inequalities persist, so will inequalities in HIV testing uptake - by any means.