Penile-scrotal erythrodysesthesia among rectal cancer patients receiving fluoropyrimidine-based chemoradiation: a case report series.

BACKGROUND: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine. CASE PRESENTATION: We identified five cases of moderate to severe penis and scrotal erythrodysesthesia over a 2-year period at a large tertiary cancer center, representing an estimated incidence of 3.6% among male patients with rectal cancer who were treated with fluoropyrimidine-based chemoradiation within our institution. CONCLUSIONS: Improved understanding of erythrodysesthesia involving the penis and scrotum can facilitate early identification and treatment of symptoms, and possibly prevent the discontinuation or delay of cancer treatment in patients treated with capecitabine and similar drugs. These clinical advances would improve and prolong patient quality of life during cancer treatment and prevent complications that result in hospitalization.

Optimising paediatric bedside teaching for medical students.

Bedside teaching is a common teaching modality in undergraduate and postgraduate curricula and involves students being supervised in a clinical interaction at a patient's bedside by a more senior clinician. Following the clinical encounter, the students and teacher discuss the case and students' consultation skills. This is of particular value in teaching paediatrics to medical students, for whom paediatrics is an unfamiliar environment, and the approach to consultation is very different to usual adult practice. Junior doctors are often tasked with teaching medical students, either in structured bedside teaching sessions during formal teaching roles, or in ad hoc sessions with students shadowing on clinical placements. As paediatrics may be unfamiliar to the junior doctors themselves, offering teaching to medical students may cause some anxiety in their own ability and knowledge. This article provides doctors in paediatrics with an insight into the evidence base underlying paediatric bedside teaching, including model structures for bedside teaching and debriefing after the session, with the aims of improving their confidence in undertaking these sessions and improving their learners' and their own yield of learning.

Wheat photosystem II heat tolerance: evidence for genotype-by-environment interactions.

High temperature stress inhibits photosynthesis and threatens wheat production. One measure of photosynthetic heat tolerance is Tcrit - the critical temperature at which incipient damage to photosystem II (PSII) occurs. This trait could be improved in wheat by exploiting genetic variation and genotype-by-environment interactions (GEI). Flag leaf Tcrit of 54 wheat genotypes was evaluated in 12 thermal environments over 3 years in Australia, and analysed using linear mixed models to assess GEI effects. Nine of the 12 environments had significant genetic effects and highly variable broad-sense heritability (H2 ranged from 0.15 to 0.75). Tcrit GEI was variable, with 55.6% of the genetic variance across environments accounted for by the factor analytic model. Mean daily growth temperature in the month preceding anthesis was the most influential environmental driver of Tcrit GEI, suggesting biochemical, physiological and structural adjustments to temperature requiring different durations to manifest. These changes help protect or repair PSII upon exposure to heat stress, and may improve carbon assimilation under high temperature. To support breeding efforts to improve wheat performance under high temperature, we identified genotypes superior to commercial cultivars commonly grown by farmers, and demonstrated potential for developing genotypes with greater photosynthetic heat tolerance.

Review: The Chemistry, Toxicity and Antibacterial Activity of Curcumin and Its Analogues.

Antimicrobial resistance is a global challenge that is already exacting a heavy price both in terms of human health and financial cost. Novel ways of approaching this crisis include the investigation of natural products. Curcumin is the major constituent in turmeric, and it is commonly used in the preparation of Asian cuisine. In addition, it possesses a wide range of pharmacological properties. This review provides a detailed account of curcumin and its analogues' antibacterial activity against both gram-positive and gram-negative isolates, including its potential mechanism(s) of action and the safety and toxicity in human and animal models. We also highlight the key challenges in terms of solubility/bioavailability associated with the use of curcumin and include research on how these challenges have been overcome.

WGNAM: whole-genome nested association mapping.

KEY MESSAGE: A powerful QTL analysis method for nested association mapping populations is presented. Based on a one-stage multi-locus model, it provides accurate predictions of founder specific QTL effects. Nested association mapping (NAM) populations have been created to enable the identification of quantitative trait loci (QTL) in different genetic backgrounds. A whole-genome nested association mapping (WGNAM) method is presented to perform QTL analysis in NAM populations. The WGNAM method is an adaptation of the multi-parent whole genome average interval mapping approach where the crossing design is incorporated through the probability of inheriting founder alleles for every marker across the genome. Based on a linear mixed model, this method provides a one-stage analysis of raw phenotypic data, molecular markers, and crossing design. It simultaneously scans the whole-genome through an iterative process leading to a model with all the identified QTL while keeping the false positive rate low. The WGNAM approach was assessed through a simulation study, confirming to be a powerful and accurate method for QTL analysis for a NAM population. This novel method can also accommodate a multi-reference NAM (MR-NAM) population where donor parents are crossed with multiple reference parents to increase genetic diversity. Therefore, a demonstration is presented using a MR-NAM population for wheat (Triticum aestivum L.) to perform a QTL analysis for plant height. The strength and size of the putative QTL were summarized enhancing the understanding of the QTL effects depending on the parental origin. Compared to other methods, the proposed methodology based on a one-stage analysis provides greater power to detect QTL and increased accuracy in the estimation of their effects. The WGNAM method establishes the basis for accurate QTL mapping studies for NAM and MR-NAM populations.

A Novel Approach to the Design and Analysis of Field Experiments to Study Variation in the Tolerance and Resistance of Cultivars to Root Lesion Nematodes (Pratylenchus spp.).

The root lesion nematode (RLN) species Pratylenchus thornei and P. neglectus are widely distributed within cropping regions of Australia and have been shown to limit grain production. Field experiments conducted to compare the performance of cultivars in the presence of RLNs investigate management options for growers by identifying cultivars with resistance, by limiting nematode reproduction, and tolerance, by yielding well in the presence of nematodes. A novel experimental design approach for RLN experiments is proposed where the observed RLN density, measured prior to sowing, is used to condition the randomization of cultivars to field plots. This approach ensured that all cultivars were exposed to consistent ranges of RLN in order to derive valid assessments of relative cultivar tolerance and resistance. Using data from a field experiment designed using the conditioned randomization approach and conducted in Formartin, Australia, the analysis of tolerance and resistance was undertaken in a linear mixed model framework. Yield response curves were derived using a random regression approach and curves modeling change in RLN densities between sowing and harvest were derived using splines to account for nonlinearity. Groups of cultivars sharing similar resistance levels could be identified. A comparison of slopes of yield response curves of cultivars belonging to the same resistance class identified differing tolerance levels for cultivars with equivalent exposures to both presowing and postharvest RLN densities. As such, the proposed design and analysis approach allowed tolerance to be assessed independently of resistance.

Fifteen-minute consultation: Kawasaki disease: how to distinguish from other febrile illnesses: tricks and tips.

Kawasaki disease (KD) is challenging to diagnose because there is no specific laboratory test and the presentation is often similar to common childhood infections. We highlight some of those KD diagnostic challenges. KD, a self-limiting vasculitis, can cause coronary artery aneurysms. The aim is to optimise management during the acute febrile illness to try and prevent these because a giant coronary artery aneurysm is devastating enough without thinking that it might have been prevented. The conundrum for acute paediatricians is which clinical features best distinguish the febrile child with possible KD, needing intravenous immunoglobulin, from the many other children with febrile illnesses.

Pediatric Erythromelalgia and SCN9A Mutations: Systematic Review and Single-Center Case Series.

OBJECTIVES: To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Nav1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations. STUDY DESIGN: PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood. Clinical features, management, and genotype were extracted. Case notes of pediatric patients with erythromelalgia from the Great Ormond Street Hospital Pain Service were reviewed for clinical features, patient-reported outcomes, and treatments. Children aged over 10 years were recruited for quantitative sensory testing. RESULTS: Twenty-eight publications described erythromelalgia associated with 15 different SCN9A gene variants in 25 children. Pain was severe and often refractory to multiple treatments, including nonspecific sodium channel blockers. Skin damage or other complications of cold immersion for symptomatic relief were common (60%). SCN9A mutations resulting in greater hyperpolarizing shifts in Nav1.7 sodium channels correlated with symptom onset at younger ages (P = .016). Variability in reporting, and potential publication bias toward severe cases, limit any estimations of overall prevalence. In our case series, symptoms were similar but comorbidities were more common in children with SCN9A mutations. Quantitative sensory testing revealed marked dynamic warm allodynia. CONCLUSIONS: Inherited erythromelalgia in children is associated with difficult-to-manage pain and significant morbidity. Standardized reporting of outcome and management in larger series will strengthen identification of genotype-phenotype relationships. More effective long-term therapies are a significant unmet clinical need.

Using Yield Response Curves to Measure Variation in the Tolerance and Resistance of Wheat Cultivars to Fusarium Crown Rot.

The disease crown rot, caused predominantly by the fungal pathogen Fusarium pseudograminearum, is a major disease of winter cereals in many regions of the world, including Australia. A methodology is proposed, using response curves, to robustly estimate the relationship between grain yield and increasing crown rot pathogen burdens. Using data from a field experiment conducted in northern New South Wales, Australia in 2016, response curves were derived for five commercial wheat cultivars exposed to six increasing rates of crown rot inoculum, where the rates served to establish a range of crown rot pathogen burdens. In this way, the response curve methodology is fundamentally different from alternate approaches that rely on genetic or environmental variation to establish a range in pathogen burdens over which yield loss relationships are estimated. By manipulating only the rates of crown rot inoculum and, thus, pathogen burden directly, the number of additional confounding factors and interactions are minimized, enabling the robust estimation of the rate of change in yield due to increasing crown rot pathogen burdens for each cultivar. The methodology revealed variation in the rate of change in yield between cultivars, along with the extent of crown rot symptoms expressed by the cultivars. Variation in the rate of change in yield between cultivars provides definitive evidence of differences in the tolerance of commercial Australian wheat cultivars to crown rot caused by F. pseudograminearum, while variation in the extent of crown rot symptoms signifies differences in the resistance of the cultivars to this disease. The response curve methodology also revealed variation in how the different mechanisms of tolerance and resistance act to limit yield losses due to crown rot for different cultivars.

Think about the 'C' (in custard and crackers).

CASE HISTORY: A 9-year-old girl with autistic spectrum disorder (ASD) was admitted for a flare-up of chronic recurrent multi-osteomyelitis (CRMO). She complained of leg pain over 3 months, was unable to weight-bear and had a petechial rash for 10 days. She had bleeding gums and a long history of only eating custard and crackers.CRMO was diagnosed at age 3. She'd had shoulder, knee, and ankle involvement, two courses of pamidronate (2011 and 2015) and was currently taking simple analgesia.On examination, she was afebrile, with a widespread petechial rash, most pronounced over her ankles/shins. Her knees and ankles were tender; her ankles had small medial effusions. INVESTIGATIONS: Mild hypochromic anaemia, normal platelets, white cell countand coagulation. CRP 16. Figures 1 and 2 show her knee radiograph and MRI, respectively.edpract;103/6/304/F1F1F1Figure 1edpract;103/6/304/F2F2F2Figure 2 QUESTION 1: Give four differential diagnoses of petechial rash, bleeding gums and leg pain in an afebrile child? QUESTION 2: Name three behaviours associated with ASD with health consequences. Answers to the questions are on page 02 ANSWERS TO THE QUESTIONS ON PAGE 02.

Seroepidemiological and phylogenetic characterization of neurotropic enteroviruses in Ireland, 2005-2014.

Enteroviruses (EVs) are associated with a broad spectrum of clinical presentation, including aseptic meningitis (AM), encephalitis, hand, foot and mouth disease, acute flaccid paralysis, and acute flaccid myelitis. Epidemics occur sporadically and are associated with increased cases of AM in children. The present study describes the seroepidemiological analysis of circulating EVs in Ireland from 2005 to 2014 and phylogenetic characterization of echovirus 30 (E-30), enterovirus A71 (EV-A71), and enterovirus D68 (EV-D68). EV VP1 genotyping was applied to viral isolates and clinical samples, including cerebrospinal fluid (CSF), and those isolates that remained untypeable by neutralising anti-sera. An increase in AM cases from 2010 to 2014 was associated with an E-30 genogroup variant VII and sequences clustered phylogenetically with those detected in AM outbreaks in France and Italy. EV-D68 viral RNA was not detected in CSF samples and no neurological involvement was reported. Three EV-A71 positive CSF samples were identified in patients presenting with AM. A phylogenetic analysis of respiratory-associated EV-D68 and EV-A71 cases in circulation was performed to determine baseline epidemiological data. EV-D68 segregated with clades B and B(1) and EV-A71 clustered as subgenogroup C2. The EV VP1 genotyping method was more sensitive than neutralising anti-sera methods by virus culture and importantly demonstrated concordance between EV genotypes in faecal and CSF samples which should facilitate EV screening by less invasive sampling approaches in AM presentations.

Determination of Orientation and Practice Requirements When Using an Obstacle Course for Mobility Performance Assessment.

OBJECTIVE: Determine effect of orientation (introduction and familiarization) and practice (repeated performance) on human performance under various load conditions as assessed by an obstacle course. BACKGROUND: Obstacle courses are commonly used as screening tools by military, police, and firefighters or to assess human capabilities and the effect of wearing personal protective equipment (PPE) and other occupationally necessary equipment on mobility task performance. Unfortunately, little is formally documented about the effect of orientation and practice on performance outcomes of obstacle or mobility courses being used. METHOD: Forty-eight participants were recruited from the Canadian Army Infantry and Combat Engineer population. Participants either received regular or extensive orientation of the course before completing it. Following orientation, participants completed the course five consecutive times while wearing their PPE with full fighting order (FFO) and five consecutive times while wearing no PPE and non-FFO across a five-day period (maximum two runs per day), with ensemble presentation order counterbalanced. Total course completion time and individual obstacle completion times were measured for each run of the course. RESULTS: While wearing FFO, participants continued to decrease the time required for completing the course; however, while wearing non-FFO, time to course completion did not significantly change over the five runs. There were no differences in course completion times for the regular and extensive course orientation groups. CONCLUSIONS: Considerations required to mitigate orientation and practicing effects can differ depending on type or complexity of load condition. While wearing FFO, practicing effects can introduce undesired confounding factors into data collection. APPLICATION: Any practice runs on an obstacle course prior to its use as an assessment tool should focus on the loaded (e.g., FFO) condition because improvement on loaded runs is likely transferred to unloaded, but this does not apply in the reverse.

Preparing for a Nursing and Midwifery Council visit in the community setting.

Preparing for a Nursing and Midwifery Council placement monitoring visit can appear daunting if practitioners have not previously participated in the process. This paper identifies why visits are required and how practitioners and the local higher education provider representatives can work together to prepare. Based on the experience of the authors it is proposed that the visit is an opportunity to disseminate good practice linked to the education and mentorship of students. Suggestions linked to successful preparation are also shared to assist community nurse teams who encounter the process in the future. It is advocated that feedback from the visit can be used to further strengthen the practice learning experience for both mentors and students.

Enhancement of antimicrobial activities of whole and sub-fractionated white tea by addition of copper (II) sulphate and vitamin C against Staphylococcus aureus; a mechanistic approach.

BACKGROUND: Enhancement of antimicrobial plant products e.g. pomegranate extract by copper (II) sulphate is known. Such combinations have applications in various settings, including the identification of novel compositions to study, treat and control infection. METHODS: A combination of white tea (WT) (made allowing 10 minutes infusion time at 100°C) was combined with 4.8 mM copper (II) sulphate and tested for antimicrobial effect on the viability of Staphylococcus aureus NCTC 06571. Comparisons were made with green (GT) and black (BT) teas. A WT sub-fraction (WTF < 1000 Da) was tested with copper (II) sulphate and 4.8 mM vitamin C. pH measurements of samples were taken for controls and to observe any changes due to tea/agent interaction. Catalase was used to investigate hydrogen peroxide release. UV-vis. was used to compare WT and WTF. RESULTS: A 30 minute incubation at room temperature of copper (II) sulphate alone and combined with WT reduced the viability of S. aureus NCTC 06571 by c.a 1 log10 cfu mL-1. GT and BT with copper (II) sulphate negated activity to buffer values. Combined with copper (II) sulphate, vitamin C, WTF and, vitamin C plus WTF all reduced the viability of S. aureus NCTC 06571 by c.a. 3.5 log10 cfu mL-1. Independent experiments showed the results were not due to pH effects. Adding WT or WTF to copper (II) sulphate resulted in increased acidity. Copper (II) sulphate alone and combined with WT required c.a 300 µg mL-1 (final concentration) catalase to restore S. aureus viability, WTF with copper (II) sulphate and added vitamin C required c.a 600 µg mL-1. WT and WTF UV-visible spectra were similar. CONCLUSIONS: WT showed no efficacy in the combinations tested. WTF was enhanced with copper (II) sulphate and further with vitamin C. WT and WTF increased acidity of copper (II) sulphate possibly via the formation of chemical complexes. The difference in WT/WTF absorbance possibly represented substances less concentrated or absent in WTF. Investigations to establish which WTF component/s and in what proportions additives are most effective against target organisms are warranted.

Designing authentic simulations in ROSE and EBUS for undergraduate laboratory medicine students.

Introduction: Simulation-based education (SBE) has successfully been implemented in several healthcare professions, more so in the fields of medicine and nursing. Laboratory medicine courses prepare medical scientists for employment in pathology laboratories typically via a staged training regime. Laboratory techniques related to the diagnostic disciplines are introduced to students in a graduated fashion over time for the development of professional skills and technical competencies. For students specialising in diagnostic cytology, there are continual changes to the scope of practice of scientists in industry that require advanced training at undergraduate level to meet expectations of contemporary laboratory testing. Methods: The National Health Education and Training in Simulation (NHET-Sim) framework was applied to create and deliver bespoke simulations for laboratory medicine students. This paper outlines the steps taken, including working with actors and industry partners, to create simulations which contextualise the pressures and team interactions during diagnostic procedures. Findings: Supported by a range of expertise and personnel, five laboratory medicine simulations were developed and delivered to final year students. Details of the steps taken and range of scenarios are included for sharing and discussion. Discussion: SBE can contribute positively to student confidence in communication at interdisciplinary and interprofessional levels in ways that can be essential to successful patient management. Understanding that cytology has now evolved to become part of a multidisciplinary approach to patient-centred care will improve the overall patient outcome and experience to personalised medicine. Conclusion: This paper demonstrates how a high-fidelity SBE scenario can test students' decision-making around technical, clinical and diagnostic competencies in a complex investigation that they would likely experience in industry.

Determination of metabolic activity in planktonic and biofilm cells of Mycoplasma fermentans and Mycoplasma pneumoniae by nuclear magnetic resonance.

Mycoplasmas are fastidious microorganisms, typically characterised by their restricted metabolism and minimalist genome. Although there is reported evidence that some mycoplasmas can develop biofilms little is known about any differences in metabolism in these organisms between the growth states. A systematic metabolomics approach may help clarify differences associated between planktonic and biofilm associated mycoplasmas. In the current study, the metabolomics of two different mycoplasmas of clinical importance (Mycoplasma pneumoniae and Mycoplasma fermentans) were examined using a novel approach involving nuclear magnetic resonance spectroscopy and principle component analysis. Characterisation of metabolic changes was facilitated through the generation of high-density metabolite data and diffusion-ordered spectroscopy that provided the size and structural information of the molecules under examination. This enabled the discrimination between biofilms and planktonic states for the metabolomic profiles of both organisms. This work identified clear biofilm/planktonic differences in metabolite composition for both clinical mycoplasmas and the outcomes serve to establish a baseline understanding of the changes in metabolism observed in these pathogens in their different growth states. This may offer insight into how these organisms are capable of exploiting and persisting in different niches and so facilitate their survival in the clinical setting.

Proteomics reveals commitment to germination in barley seeds is marked by loss of stress response proteins and mobilisation of nutrient reservoirs.

Germination is a critical process in the reproduction and propagation of flowering plants, and is also the key stage of industrial grain malting. Germination commences when seeds are steeped in water, followed by degradation of the endosperm cell walls, enzymatic digestion of starch and proteins to provide nutrients for the growing plant, and emergence of the radicle from the seed. Dormancy is a state where seeds fail to germinate upon steeping, but which prevents inappropriate premature germination of the seeds before harvest from the field. This can result in inefficiencies in industrial malting. We used Sequential Window Acquisition of all THeoretical ions Mass Spectrometry (SWATH-MS) proteomics to measure changes in the barley seed proteome throughout germination. We found a large number of proteins involved in desiccation tolerance and germination inhibition rapidly decreased in abundance after imbibition. This was followed by a decrease in proteins involved in lipid, protein and nutrient reservoir storage, consistent with induction and activation of systems for nutrient mobilisation to provide nutrients to the growing embryo. Dormant seeds that failed to germinate showed substantial biochemical activity distinct from that of seeds undergoing germination, with differences in sulfur metabolic enzymes, endogenous alpha-amylase/trypsin inhibitors, and histone proteins. We verified our findings with analysis of germinating barley seeds from two commercial malting facilities, demonstrating that key features of the dynamic proteome of germinating barley seeds were conserved between laboratory and industrial scales. The results provide a more detailed understanding of the changes in the barley proteome during germination and give possible target proteins for testing or to inform selective breeding to enhance germination or control dormancy. SIGNIFICANCE: Germination is critical to the reproduction and propagation of flowering plants, and in industrial malting. Dormancy, where seeds fail to germinate upon steeping, can result in inefficiencies in industrial malting. Our DIA/SWATH-MS proteomics analyses identified key changes during germination, including an initial loss of proteins involved in desiccation tolerance and germination inhibition, followed by decreases in lipid, protein and nutrient reservoir storage. These changes were consistent between laboratory and industrial malting scales, and therefore demonstrate the utility of laboratory-scale barley germination as a model system for industrial malt house processes. We also showed that dormant seeds that failed to germinate showed substantial biochemical activity distinct from that of seeds undergoing germination, consistent with dormancy being an actively regulated state. Our results provide a more detailed understanding of the changes in the barley proteome during germination and give possible target proteins for testing or to inform selective breeding to enhance germination or control dormancy.

Visualisation and biovolume quantification in the characterisation of biofilm formation in Mycoplasma fermentans.

The ability of mycoplasmas to persist on surfaces has been widely acknowledged, despite their fastidious nature. However, the organism's capability to form a recognisable biofilm structure has been identified more recently. In the current study Mycoplasma fermentans was found to adhere to the glass surface forming highly differentiated biofilm structures. The volumes of biofilm microcolonies were quantified and observed to be greater at late growth stage than those at early growth stage. The channel diameters within biofilms were measured with Scanning Electron Microscopy images and found to be consistent with the size observed in Confocal Laser Scanning Microscope images. The combination of imaging methods with 3D visualisation provides key findings that aid understanding of the mycoplasma biofilm formation and true biofilm architecture. The observations reported here provide better understanding of the persistence of these minimalist pathogens in nature and clinical settings.