Diversity of thought: public perceptions of genetic testing across ethnic groups in the UK.

Genetic testing is becoming rapidly more accessible to the general populous either through or outside healthcare systems. Few large-scale studies have been carried out to gauge public opinion in this growing area. Here, we undertook the largest cross-sectional study on genetic testing in the UK. The primary purpose of this study is to identify the differences in attitudes toward genetic testing across ethnic groups. A cohort of 6500 individuals from a diverse population completed a 72-item survey in a cross-sectional study. Responses between ethnic minority and white individuals in the UK were compared using a wilcoxon rank-sum and chi-square tests. The white cohort was approximately twice as likely to have taken a genetic test and 13% more had heard about genetic testing before the survey. The ethnic minority cohort appeared more apprehensive about the impact of genetic testing on employability. This study highlights that in the UK, significant differences in opinions regarding genetic testing exist between white individuals and ethnic minority individuals. There is an urgent need to develop more inclusive strategies to equally inform individuals from all backgrounds to avoid disparities in the utilisation of genetic testing.

Twelve tips for designing and implementing peer-led assessment writing schemes in health professions education.

Peer-led assessment (PLA) has gained increasing prominence within health professions education as an effective means of engaging learners in the process of assessment writing and practice. Involving students in various stages of the assessment lifecycle, including item writing, quality assurance, and feedback, not only facilitates the creation of high-quality item banks with minimal faculty input but also promotes the development of students' assessment literacy and fosters their growth as teachers. The advantages of involving students in the generation of assessments are evident from a pedagogical standpoint, benefiting both students and faculty. However, faculty members may face uncertainty when it comes to implementing such approaches effectively. To address this concern, this paper presents twelve tips that offer guidance on important considerations for the successful implementation of peer-led assessment schemes in the context of health professions education.

Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of the protein dystrophin. Gene therapy strategies that aim to increase expression of a functional dystrophin protein (mini-dystrophin) are under investigation. The ability to accurately quantify dystrophin/mini-dystrophin is essential in assessing the level of gene transduction. We demonstrated the validation and application of a novel peptide immunoaffinity liquid chromatography-tandem mass spectrometry (IA-LC-MS/MS) assay. Data showed that dystrophin expression in Becker muscular dystrophy and DMD tissues, normalized against the mean of non-dystrophic control tissues (n = 20), was 4-84.5% (mean 32%, n = 20) and 0.4-24.1% (mean 5%, n = 20), respectively. In a DMD rat model, biceps femoris tissue from dystrophin-deficient rats treated with AAV9.hCK.Hopti-Dys3978.spA, an adeno-associated virus vector containing a mini-dystrophin transgene, showed a dose-dependent increase in mini-dystrophin expression at 6 months post-dose, exceeding wildtype dystrophin levels at high doses. Validation data showed that inter- and intra-assay precision were ≤20% (≤25% at the lower limit of quantification [LLOQ]) and inter- and intra-run relative error was within ±20% (±25% at LLOQ). IA-LC-MS/MS accurately quantifies dystrophin/mini-dystrophin in human and preclinical species with sufficient sensitivity for immediate application in preclinical/clinical trials.

Phenotyping for waterlogging tolerance in crops: current trends and future prospects.

Yield losses to waterlogging are expected to become an increasingly costly and frequent issue in some regions of the world. Despite the extensive work that has been carried out examining the molecular and physiological responses to waterlogging, phenotyping for waterlogging tolerance has proven difficult. This difficulty is largely due to the high variability of waterlogging conditions such as duration, temperature, soil type, and growth stage of the crop. In this review, we highlight use of phenotyping to assess and improve waterlogging tolerance in temperate crop species. We start by outlining the experimental methods that have been utilized to impose waterlogging stress, ranging from highly controlled conditions of hydroponic systems to large-scale screenings in the field. We also describe the phenotyping traits used to assess tolerance ranging from survival rates and visual scoring to precise photosynthetic measurements. Finally, we present an overview of the challenges faced in attempting to improve waterlogging tolerance, the trade-offs associated with phenotyping in controlled conditions, limitations of classic phenotyping methods, and future trends using plant-imaging methods. If effectively utilized to increase crop resilience to changing climates, crop phenotyping has a major role to play in global food security.

A speckle-tracking strain-based artificial neural network model to differentiate cardiomyopathy type.

Objectives. In heart failure, invasive angiography is often employed to differentiate ischaemic from non-ischaemic cardiomyopathy. We aim to examine the predictive value of echocardiographic strain features alone and in combination with other features to differentiate ischaemic from non-ischaemic cardiomyopathy, using artificial neural network (ANN) and logistic regression modelling. Design. We retrospectively identified 204 consecutive patients with an ejection fraction <50% and a diagnostic angiogram. Patients were categorized as either ischaemic (n = 146) or non-ischaemic cardiomyopathy (n = 58). For each patient, left ventricular strain parameters were obtained. Additionally, regional wall motion abnormality, 13 electrocardiographic (ECG) features and six demographic features were retrieved for analysis. The entire cohort was randomly divided into a derivation and a validation cohort. Using the parameters retrieved, logistic regression and ANN models were developed in the derivation cohort to differentiate ischaemic from non-ischaemic cardiomyopathy, the models were then tested in the validation cohort. Results. A final strain-based ANN model, full feature ANN model and full feature logistic regression model were developed and validated, F1 scores were 0.82, 0.79 and 0.63, respectively. Conclusions. Both ANN models were more accurate at predicting cardiomyopathy type than the logistic regression model. The strain-based ANN model should be validated in other cohorts. This model or similar models could be used to aid the diagnosis of underlying heart failure aetiology in the form of the online calculator (https://cimti.usj.edu.lb/strain/index.html) or built into echocardiogram software.

Pediatric Drowning: A Standard Operating Procedure to Aid the Prehospital Management of Pediatric Cardiac Arrest Resulting From Submersion.

OBJECTIVES: Drowning is one of the leading causes of death in children. Resuscitating a child following submersion is a high-pressure situation, and standard operating procedures can reduce error. Currently, the Resuscitation Council UK guidance does not include a standard operating procedure on pediatric drowning. The objective of this project was to design a standard operating procedure to improve outcomes of drowned children. METHODS: A literature review on the management of pediatric drowning was conducted. Relevant publications were used to develop a standard operating procedure for management of pediatric drowning. RESULTS: A concise standard operating procedure was developed for resuscitation following pediatric submersion. Specific recommendations include the following: the Heimlich maneuver should not be used in this context; however, prolonged resuscitation and therapeutic hypothermia are recommended. CONCLUSIONS: This standard operating procedure is a potentially useful adjunct to the Resuscitation Council UK guidance and should be considered for incorporation into its next iteration.

Hereditary haemorrhagic telangiectasia with multiple complications presenting in an older patient.

Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant multi-organ vascular disorder associated with bleeding and a reduced life expectancy. We present a 91-year-old woman with complications of previously undiagnosed HHT. This case demonstrates three potential complications: pulmonary arteriovenous malformation (AVM) resulting in a right to left shunt, cerebral infarctions and pericardial effusion. Despite these potentially life-threatening complications and the reduced life-expectancy associated with HHT the patient has survived to an advanced age. Due to the patient's late diagnosis and frailty, the treatment options of AVM embolization and pericardiocentesis were deemed inappropriate. The patient was treated with tranexamic acid to reduce bleeding severity and discharged home with a care package and home oxygen.

Formative student-authored question bank: perceptions, question quality and association with summative performance.

PURPOSE OF THE STUDY: There are few studies on the value of authoring questions as a study method, the quality of the questions produced by students and student perceptions of student-authored question banks. Here we evaluate PeerWise, a widely used and free online resource that allows students to author, answer and discuss multiple-choice questions. STUDY DESIGN: We introduced two undergraduate medical student cohorts to PeerWise (n=603). We looked at their patterns of PeerWise usage; identified associations between student engagement and summative exam performance; and used focus groups to assess student perceptions of the value of PeerWise for learning. We undertook item analysis to assess question difficulty and quality. RESULTS: Over two academic years, the two cohorts wrote 4671 questions, answered questions 606 658 times and posted 7735 comments. Question writing frequency correlated most strongly with summative performance (Spearman's rank: 0.24, p=<0.001). Student focus groups found that: (1) students valued curriculum specificity; and (2) students were concerned about student-authored question quality. Only two questions of the 300 'most-answered' questions analysed had an unacceptable discriminatory value (point-biserial correlation <0.2). CONCLUSIONS: Item analysis suggested acceptable question quality despite student concerns. Quantitative and qualitative methods indicated that PeerWise is a valuable study tool.

Identification of methylated metabolites of oat avenanthramides in human plasma using UHPLC QToF-MS.

Oat avenanthramides (AVAs) are a group of phenolic alkaloids, consisting of an anthranilic acid and a hydroxycinnamic acid linked by a pseudo-peptide bond. Bioavailability of AVA is poor in humans, suggesting transformations for rapid excretion. Thus, we aim to identify metabolites of AVA isomers in plasma of humans after consuming AVA-enriched oats. After lipid removal, AVA and their metabolites in plasma were extracted with ethyl acetate and analysed using an Agilent UHPLC-QToF-MS. Pharmacokinetics of AVA-O showed a bimodal distribution with Cmax1 and 2 for AVA-O at 5.9 ± 5.2 and 7.9 ± 7.0 ng/mL and Tmax1 and 2 at 1.7 ± 0.7 and 3.1 ± 1.2 h, respectively. Only the methyl-AVA-O showed a single Cmax at 14 ± 9.9 ng/mL AVA-O equivalents and a Tmax of 2.4 ± 2.7 h. This analysis is the first to identify methylated metabolites of AVAs and AVA aglycones in human blood after acute AVA consumption.

Waterpipe smoking and risk of coronary artery disease.

PURPOSE OF REVIEW: Smoking tobacco using a water pipe is becoming more prevalent globally, particularly amongst younger populations. In addition to its growing popularity, more evidence is emerging regarding associated harm, and several misconceptions exist concerning the likely adverse health effects of waterpipe smoking (WPS). It is timely, therefore, to examine the body of evidence linking WPS to coronary artery disease (CAD). Here, we review the direct evidence linking WPS to CAD and examine additional, indirect evidence of associated harm. We discuss the clinical and public health implications of the current evidence and provide suggestions for further research. RECENT FINDINGS: A multicentre case-control study in Lebanon has recently demonstrated an association between WPS and CAD. There are few prior studies making this direct link. However, a large body of evidence has emerged showing close similarities between WPS and cigarette smoking with regard to the toxicity of smoke and acute inflammatory and haemodynamic effects following exposure to it. SUMMARY: There are consistent similarities between WPS and cigarette smoking in regard to association with CAD, the nature of the smoke produced, and the acute haemodynamic effects and inflammatory responses that follow exposure. These findings justify both public health and clinical interventions to reduce WPS. Further studies are warranted to confirm a causal association between WPS and CAD.

Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake.

The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric method for the quantification of the proanthocyanin dimer A-2 in human urine and validate urinary proanthocyanin dimer A-2 as a biomarker of cranberry intake. Five healthy, nonsmoking, premenopausal women (20-30 years of age, body mass index: 18.5-25 kg/m(2) ) were assigned to consume a cranberry beverage containing 140 mg proanthocyanin and 35 kilocalories at 237 mL/day, according to a weekly dosing schedule for 7 weeks. Eleven 24 h and morning spot urine samples each were collected from each subject. A reliable, sensitive method for the detection of proanthocyanin dimer A-2 in urine using liquid chromatography with tandem mass spectrometry was developed with a limit of quantitation of 0.25 ng/mL and a relative standard deviation of 7.26%, precision of 5.7%, and accuracy of 91.7%. While proanthocyanin dimer A-2 was quantifiable in urine, it did not appear to be excreted in a concentration that corresponded to the dosing schedule and intake of cranberry juice.

Wünderlich ist nicht so Wunderbar: Bilateral Angiomyolipomas and Wünderlich Syndrome Requiring Emergency Embolization in a Patient without Tuberous Sclerosis.

Bilateral renal angiomyolipomata are rare and usually associated with tuberous sclerosis. Renal angiomyolipomata can rupture spontaneously giving rise to (potentially catastrophic) retroperitoneal hemorrhage (Wünderlich syndrome). We present a very rare case of bilateral renal angiomyolipomata in an individual without tuberous sclerosis, presenting with life-threatening hemorrhage. The patient had emergency embolization of the bleeding angiomyolipoma and received elective embolization of a contralateral lesion. A follow-up brain magnetic resonance imaging showed no tubers but revealed a pituitary adenoma of uncertain significance.

A novel student-led approach to multiple-choice question generation and online database creation, with targeted clinician input.

PROBLEM: Multiple-choice questions (MCQs) are the main method of assessing medical student knowledge. As a result there is a high demand from medical students for formative MCQs. However, teaching staff rarely have the time or incentive to develop high-quality formative questions, focusing instead on material for high-stakes assessments. INTERVENTION: We have developed a novel student-led approach involving an interactive online question database, created by medical students for medical students. We adopted a staged approach to create an online bank of formative MCQ questions. First, students write MCQs following a standardized format. Questions are then peer-reviewed by other students, discussing relevant clinical topics, guidelines, and journals to improve question quality. The questions are then scrutinized by specialist doctors and academics. Next, questions are piloted online. Finally, question performance is evaluated statistically. This 5-stage student-led process produced a bank of more than 200 MCQs in three months. CONTEXT: This intervention was carried out by two final-year medical student leads at Cardiff University School of Medicine, UK. Final-year students were recruited to write and peer-review questions, and senior content specialists were recruited from the department. After piloting and evaluation of the questions, the question bank was made available as a learning resource to all medical students at Cardiff University. OUTCOME: Objective analysis of the created MCQs (discrimination indices and distractor analysis) indicated that the random sample of questions piloted were of high quality. When the questions were made available as online tests to approximately 600 students, usage data revealed that 2,800 tests were taken over a 3-month period, indicating that the resource was popular. In addition, subjective feedback from students question writers/reviewers was gathered via free text feedback forms and was invariably positive. We plan to continue the question generation process in Cardiff and would encourage other medical schools to adopt this approach. LESSONS LEARNED: Our 5-stage approach can generate a large volume of high-quality MCQs, addressing the demand from students for formative MCQ questions, with minimal teaching staff input. The project's benefits go beyond the creation of the resource, as involving students in the writing, review, and presentation of questions itself is useful pedagogically.

Advancements in Imaging Sensors and AI for Plant Stress Detection: A Systematic Literature Review.

Integrating imaging sensors and artificial intelligence (AI) have contributed to detecting plant stress symptoms, yet data analysis remains a key challenge. Data challenges include standardized data collection, analysis protocols, selection of imaging sensors and AI algorithms, and finally, data sharing. Here, we present a systematic literature review (SLR) scrutinizing plant imaging and AI for identifying stress responses. We performed a scoping review using specific keywords, namely abiotic and biotic stress, machine learning, plant imaging and deep learning. Next, we used programmable bots to retrieve relevant papers published since 2006. In total, 2,704 papers from 4 databases (Springer, ScienceDirect, PubMed, and Web of Science) were found, accomplished by using a second layer of keywords (e.g., hyperspectral imaging and supervised learning). To bypass the limitations of search engines, we selected OneSearch to unify keywords. We carefully reviewed 262 studies, summarizing key trends in AI algorithms and imaging sensors. We demonstrated that the increased availability of open-source imaging repositories such as PlantVillage or Kaggle has strongly contributed to a widespread shift to deep learning, requiring large datasets to train in stress symptom interpretation. Our review presents current trends in AI-applied algorithms to develop effective methods for plant stress detection using image-based phenotyping. For example, regression algorithms have seen substantial use since 2021. Ultimately, we offer an overview of the course ahead for AI and imaging technologies to predict stress responses. Altogether, this SLR highlights the potential of AI imaging in both biotic and abiotic stress detection to overcome challenges in plant data analysis.

Treatment and Care of Patients with ST-Segment Elevation Myocardial Infarction-What Challenges Remain after Three Decades of Primary Percutaneous Coronary Intervention?

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Analysis of ß-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry.

ß-Nerve growth factor (NGF) is a neurotrophin that plays a critical role in fetal development during gestation. ProNGF is the precursor form of NGF with a distinct biological profile. In order to investigate the role of NGF and proNGF in pregnant human females, a sensitive and selective immunoaffinity liquid chromatography-tandem mass spectrometry assay was developed and qualified to simultaneously measure the levels of total NGF (tNGF; sum of mature and proNGF) and proNGF using full and relative quantification strategies, respectively. The assay was used to determine serum tNGF and proNGF levels in the three gestational trimesters of pregnancy and in non-pregnant female controls. Mean tNGF ± SD were 44.6 ± 12.3, 42.6 ± 9.3, 65.4 ± 17.6 and 77.0 ± 17.8 pg/mL for non-pregnant, first, second, and third trimesters, respectively, demonstrating no significant increase in circulating tNGF between the control and the first trimester, and a moderate yet significant 1.7-fold increase through gestation. proNGF levels during the first trimester were unchanged compared to control. In contrast to tNGF, however, proNGF levels during gestation remained stable without significant changes. The development of this sensitive, novel immunoaffinity duplexed assay for both tNGF and proNGF is expected to enable further elucidation of the roles these neurotrophins play in human pregnancy as well as other models.

Takotsubo syndrome and complete heart block, which came first? A case report.

BACKGROUND: In 2018, the European Society of Cardiology published two consensus documents on takotsubo syndrome (TTS), which include the current consensus on nomenclature, diagnosis, management, and complications. However, little is mentioned on the association with complete heart block (CHB), except that 'AV block [occurs in] 2.9% of cases'. Complete heart block is a recognized rare association of TTS, but causation is often unclear. Does CHB trigger TTS or vice-versa? Here, we present a case of TTS associated with CHB. CASE SUMMARY: An 89-year-old woman presented with a transient loss of consciousness, acute chest pain, and dyspnoea. A few days prior to this her daughter died suddenly of a myocardial infarction. On presentation, troponin levels were elevated, the electrocardiogram showed CHB with a broad QRS and an echo showed apical akinesis and ballooning. Angiographic investigation excluded significant coronary artery disease. A dual-chamber pacemaker was implanted after a brief period of temporary pacing. Ventricular function normalized during follow-up and her underlying rhythm remained CHB. DISCUSSION: Takotsubo syndrome may be triggered by both emotional and physical stressors. Complete heart block is recognized association, but causation is often unclear. In our case, a clear emotional trigger was identified suggesting the TTS may have precipitated CHB not vice versa.

Capturing crop adaptation to abiotic stress using image-based technologies.

Farmers and breeders aim to improve crop responses to abiotic stresses and secure yield under adverse environmental conditions. To achieve this goal and select the most resilient genotypes, plant breeders and researchers rely on phenotyping to quantify crop responses to abiotic stress. Recent advances in imaging technologies allow researchers to collect physiological data non-destructively and throughout time, making it possible to dissect complex plant responses into quantifiable traits. The use of image-based technologies enables the quantification of crop responses to stress in both controlled environmental conditions and field trials. This paper summarizes phenotyping imaging technologies (RGB, multispectral and hyperspectral sensors, among others) that have been used to assess different abiotic stresses including salinity, drought and nitrogen deficiency, while discussing their advantages and drawbacks. We present a detailed review of traits involved in abiotic tolerance, which have been quantified by a range of imaging sensors under high-throughput phenotyping facilities or using unmanned aerial vehicles in the field. We also provide an up-to-date compilation of spectral tolerance indices and discuss the progress and challenges in machine learning, including supervised and unsupervised models as well as deep learning.