DOMINO trial post hoc analysis: evaluation of the diet effects on symptoms in IBS subtypes.

Background: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by recurrent abdominal pain related to defecation and/or associated to a change in bowel habits. According to the stool type, four different IBS subtypes can be recognized, constipation predominant (IBS-C), diarrhea predominant (IBS-D), mixed (IBS-M), and undefined (IBS-U). Patients report that their IBS symptoms are exacerbated by food. Thus, it is important to find a nutritional approach that could be effective in reducing IBS symptoms. Objective: The present work is a post hoc analysis of the previously published DOMINO trial. It aimed to evaluate the effects of a self-instructed FODMAP-lowering diet smartphone application on symptoms and psychosocial aspects in primary care IBS stratifying the results for each IBS subtypes. Design: Post hoc analysis. Methods: Two hundred twenty-two primary care IBS patients followed a FODMAP-lowering diet for 8 weeks with the support of a smartphone application. Two follow-up visits were scheduled after 16 and 24 weeks. IBS-Symptoms Severity Score (IBS-SSS), quality of life (QoL), and adherence and dietary satisfaction were evaluated. Results: After 8 weeks, IBS-SSS improved in all IBS subtypes (p < 0.0001). Physician Health Questiionnaire (PHQ-15) improved only in IBS-D (p = 0.0006), whereas QoL improved both in IBS-D (p = 0.01) and IBS-M (p = 0.005). Conclusion: This post hoc analysis showed that the app is useful in all IBS subtypes; thus, it could be used as an effective tool by both general practitioners and patients to manage symptoms in primary care. Trial registration: Ethical Commission University Hospital of Leuven reference number: S59482. Clinicaltrial.gov reference number: NCT04270487.

What is already known about this subject? The low FODMAP (fermentable oligo-, di-, and monosaccharides and polyols) diet has shown efficacy for controlling IBS (irritable bowel syndrome) symptoms in small controlled trials in tertiary care patients. As this approach requires several visits with an experienced dietitian, it seems less suitable for primary care. What are the new findings? The benefit of the FODMAP lowering app was already present at 4 weeks and persisted during follow-up until 24 weeks. How might it impact on clinical practice in the foreseeable future? Given its superiority to standard first-line pharmacotherapy, and its ease of use, a FODMAP lowering app has the potential to become the preferred first-line treatment for primary care IBS.

Current prescribing for pyoderma gangrenosum in the UK and access to biologic medications: Results from a UK Dermatology Clinical Trials Network (UKDCTN) survey of UK Dermatologists.

Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of cases. The use of biologic medications to treat PG is increasing although there is a limited evidence base to guide treatment choices. In some health systems, such as the UK NHS, limitations are placed on biologic prescribing for PG leading to wide variations in prescribing. A survey of mainly UK clinicians showed that prednisolone remains the first line treatment for PG (90%). Biologics have been used by 66% of clinicians as second line therapy but 19% have had prescribing requests declined. Further research is needed to determine optimal treatment strategies for PG.

Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome.

BACKGROUND & AIMS: The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities. METHODS: Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities. RESULTS: In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose. CONCLUSION: We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.

Assessing sickness behavior in the French: Validation of the French translation of the sickness questionnaire (SicknessQ) in a non-clinical French population.

The Sickness Questionnaire (SicknessQ) is a questionnaire developed to assess symptoms of sickness behavior, including somatic, behavioral, and affective dimensions. To promote cross-cultural assessments of sickness behavior, we aim to expand the use of this questionnaire to other populations and languages. The aim of the present study was to evaluate the French translation of SicknessQ in a French-speaking general population during the COVID-19 pandemic. One hundred and thirty-nine individuals completed the SicknessQ online, along with the construct criteria measures of self-rated health, state anxiety (STAI-S), and depressive symptoms (PHQ-9). The principal component analyses revealed two components: the first component included seven items concerning mood, motivation and experiences of fatigue and pain; the second component included three items concerning somatic sickness symptoms. Higher scores on the total scale and the two component subscales were associated with poorer self-rated health and higher STAI-S and PHQ-9 scores. Since the associations with construct criteria variables were relatively similar between the single- and the two-dimensional solutions, both the total scale and the subscales of the two components of the French SicknessQ can be used in future studies to measure sickness behavior in French-speaking populations.

Do prokinetic agents provide symptom relief through acceleration of gastric emptying? An update and revision of the existing evidence.

BACKGROUND: Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions. OBJECTIVE: To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis. DESIGN: Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials. RESULTS: Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub-optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta-analysis methodology. CONCLUSIONS: The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated.

Decreased Testosterone Levels Precede a Myocardial Infarction in Both Men and Women.

The potential role of the hormone testosterone in the risk for myocardial infarction is investigated in this study of middle-aged men and women compared with a large random control sample from the general population. Radioimmunoassay was used to measure testosterone levels in hair, approximately 1 month and 3 months before an ST-elevation or non-ST-elevation acute myocardial infarction. Mean testosterone levels were measured for middle-aged men and women (n = 168) with diagnosed myocardial infarction (the acute myocardial infarction [AMI] cases). As controls, n = 3,150 randomly selected subjects from the general population of similar age were measured at 1 time point. No significant difference in testosterone levels in hair was found 3 months before AMI for men and women compared with the controls. However, 1 month before AMI, the testosterone levels were decreasing (p <0.001) for both men (from 2.84 to 2.10 pg/mg) and women (from 1.43 to 1.10 pg/mg), indicating that a decrease in testosterone concentrations precedes a severe cardiac event. Conventional cardiovascular risk factors were tested as confounders but did not alter this tendency. The AMI cases were also compared with a randomly selected second control group from the general population (n = 205), for whom comparable segmental hair analyses were conducted. A tendency of some decreasing testosterone levels, also in the small control group, was only significant for men. This control group was a small sample, and there might be some natural biologic variation in testosterone levels over time. This study indicates that decreased testosterone levels may be among the pathophysiological processes preceding myocardial infarction and merits further investigation.

Body surface gastric mapping to determine gastric motility patterns associated with delayed gastric emptying after pancreaticoduodenectomy. Gastric Electric Mapping after Pancreatoduodenectomy study protocol.

INTRODUCTION: Delayed gastric emptying (DGE) is frequent after pancreaticoduodenectomy (PD). Although often associated with postoperative pancreatic fistula, the precise pathogenesis in patients with no underlying complications remains unclear. There is evidence to suggest that, after surgery, aberrant electrical pathways are formed in the stomach which could contribute to the development of DGE.Gastric Alimetry is a novel technology which measures the electrical activity of the stomach non-invasively using an array of electrodes applied to the skin of the abdomen. This technique, termed body surface gastric mapping (BSGM), has been validated in normal controls and in patients with functional dyspepsia syndromes. This study will investigate the efficacy and feasibility of using BSGM to assess gastric motility in patients who undergo PD. METHODS AND ANALYSIS: This prospective cohort study will be conducted at a single large volume hepatobiliary unit in the UK. 50 patients who are planned to undergo PD will be included. BSGM measurement will be performed at four timepoints viz: preoperatively, day 4 postoperatively, at discharge and 6 months postoperatively. Key parameters of BSGM measurement, including wave amplitude, frequency and directional vector, will be measured at each timepoint and compared between different patient subgroups. Symptoms will be self-reported by patients during the recording using an iPad application designed for this purpose. Quality of life and patient experience will be assessed using standardised questionnaires at the end of the follow-up period. ETHICS AND DISSEMINATION: The protocol has been approved by the research ethics committees of Newcastle University and the Health Research Authority (HRA) of the UK (ethical approval IRAS ID 305302). Findings will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: This study will automatically be registered with the ISRCTN registry by the HRA as part of the ethics approval process.

Possible futures of acute medical care in the NHS: a multispecialty approach.

Changing population demographics and needs are resulting in a continual rise in acute medical admissions. This review draws on the observations of the NHS GIRFT programme across England. Fundamental aspects of acute medical care are not universally provided, resulting in preventable hospitalisation and over-use of emergency departments. Such aspects include care outside hospitals; appropriately sized, staffed, located and configured acute medical units; multispeciality same-day emergency care (SDEC) pathways; multidisciplinary care on wards; and readmission prevention. 'Hospital at home' services are developing, and require local evaluation. SDEC is expanding. Digital technologies make it possible to provide acute care in and across more settings. Addressing the fundamentals of acute medical care, evaluating new service opportunities, strong clinical and managerial partnerships, better data for analytics, and a multispeciality, multiprofessional approach will enable a better level of care to be achieved.

Efficacy of ketamine in the treatment of migraines and other unspecified primary headache disorders compared to placebo and other interventions: a systematic review.

BACKGROUND: Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of productivity on a global scale. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ketamine on migraines and other primary headache disorders compared to placebo and other active interventions, such as midazolam, metoclopramide/diphenhydramine, and prochlorperazine/diphenhydramine. METHODS: An electronic search of databases published up to February 2021, including Medline via PubMed, EMBASE, Web of Science, and Cochrane Library, a hand search of the bibliographies of the included studies, as well as literature and systematic reviews found through the search was conducted to identify randomized controlled trials (RCTs) investigating ketamine in the treatment of migraine/headache disorders compared to the placebo. The authors assessed the risk of bias according to the Cochrane Handbook guidelines. RESULTS: The initial search strategy yielded 398 unduplicated references, which were independently assessed by three review authors. After evaluation, this number was reduced to five RCTs (two unclear risk of bias and three high risk of bias). The total number of patients in all the studies was 193. Due to the high risk of bias, small sample size, heterogeneity of the outcomes reported, and heterogeneity of the comparison groups, the quality of the evidence was very low. One RCT reported that intranasal ketamine was superior to intranasal midazolam in improving the aura attack severity, but not duration, while another reported that intranasal ketamine was not superior to metoclopramide and diphenhydramine in reducing the headache severity. In one trial, subcutaneous ketamine was superior to saline in migraine severity reduction; however, intravenous (I.V.) ketamine was inferior to I.V. prochlorperazine and diphenhydramine in another study. CONCLUSION: Further double-blind controlled studies are needed to assess the efficacy of ketamine in treating acute and chronic refractory migraines and other primary headaches using intranasal and subcutaneous routes. These studies should include a long-term follow-up and different ketamine dosages in diagnosed patients following international standards for diagnosing headache/migraine.

A Pilot Study of a Sensor Enhanced Activity Management System for Promoting Home Rehabilitation Exercise Performed during the COVID-19 Pandemic: Therapist Experience, Reimbursement, and Recommendations for Implementation.

Adherence to home exercise programs (HEPs) during physical rehabilitation is usually unmonitored and is thought to be low from self-reports. This article describes exploratory implementation of a Sensor Enhanced Activity Management (SEAM) system that combines HEP management software with a movement sensor for monitoring and motivating HEP adherence. The article also presents results from attempting to gain reimbursement for home use of the system with therapist oversight using Remote Physiologic Monitoring (RPM) codes. Four therapists used the system in their regular practice during the first six months of the COVID-19 pandemic. Therapists filled out surveys, kept notes, and participated in interviews. Billing and reimbursement data were obtained from the treatment facility. Exercise data from the SEAM system were used to understand HEP adherence. Patients were active for a mean of 40% (26% SD) of prescribed days and completed a mean of 25% (25% SD) of prescribed exercises. The therapists billed 23 RPM codes (USD 2353), and payers reimbursed eight of those instances (USD 649.21). The therapists reported that remote monitoring and the use of a physical movement sensor was motivating to their patients and increased adherence. Sustained technical support for therapists will likely improve implementation of new remote monitoring and treatment systems. RPM codes may enable reimbursement for review and program management activities, but, despite COVID-19 CMS waivers, organizations may have more success if these services are billed under supervision of a physician.

Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms.

Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32-37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13-2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.

Role of smoking in functional dyspepsia and irritable bowel syndrome: three random population-based studies.

BACKGROUND: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients. AIM: To assess if smoking is an independent risk factor for FD and IBS. METHODS: Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex. RESULTS: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed. CONCLUSION: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.

A Pilot Evaluation of mHealth App Accessibility for Three Top-Rated Weight Management Apps by People with Disabilities.

Growing evidence demonstrates that people with disabilities face more challenges in accessing healthcare and wellness resources, compared to non-disabled populations. As mobile applications focused on health and wellness (mHealth apps) become prevalent, it is important that people with disabilities can access and use mHealth apps. At present, there is no source of unified information about the accessibility and usability of mHealth apps for people with disabilities. We set out to create such a source, establishing a systematic approach for evaluating app accessibility. Our goal was to develop a simple, replicable app evaluation process to generate useful information for people with disabilities (to aid suitable app selection) and app developers (to improve app accessibility and usability). We collected data using two existing assessment instruments to test three top-rated weight management apps with nine users representing three disability groups: vision, dexterity, and cognitive impairment. Participants with visual impairments reported the lowest accessibility ratings, most challenges, and least tolerance for issues. Participants with dexterity impairments experienced significant accessibility-related difficulties. Participants with cognitive impairments experienced mild difficulties and higher tolerances for issues. Our pilot protocol will be applied to test mHealth apps and populate a "curation" website to assist consumers in selecting mHealth apps.

A Machine Learning Enhanced Mechanistic Simulation Framework for Functional Deficit Prediction in TBI.

Resting state functional magnetic resonance imaging (rsfMRI), and the underlying brain networks identified with it, have recently appeared as a promising avenue for the evaluation of functional deficits without the need for active patient participation. We hypothesize here that such alteration can be inferred from tissue damage within the network. From an engineering perspective, the numerical prediction of tissue mechanical damage following an impact remains computationally expensive. To this end, we propose a numerical framework aimed at predicting resting state network disruption for an arbitrary head impact, as described by the head velocity, location and angle of impact, and impactor shape. The proposed method uses a library of precalculated cases leveraged by a machine learning layer for efficient and quick prediction. The accuracy of the machine learning layer is illustrated with a dummy fall case, where the machine learning prediction is shown to closely match the full simulation results. The resulting framework is finally tested against the rsfMRI data of nine TBI patients scanned within 24 h of injury, for which paramedical information was used to reconstruct in silico the accident. While more clinical data are required for full validation, this approach opens the door to (i) on-the-fly prediction of rsfMRI alterations, readily measurable on clinical premises from paramedical data, and (ii) reverse-engineered accident reconstruction through rsfMRI measurements.

Duodenal eosinophilia and the link to anxiety: A population-based endoscopic study.

INTRODUCTION: The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety. METHODS: Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1st (D1) and 2nd portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value. RESULTS: The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046). CONCLUSION: Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD.

Standard Modifiable Cardiovascular Risk Factors Mediate the Association Between Elevated Hair Cortisol Concentrations and Coronary Artery Disease.

BACKGROUND: Increased cortisol exposure is a risk factor for coronary artery disease (CAD). It is not clear to what degree this risk is independent from the standard modifiable risk factors (SMuRFs) dyslipidemia, hypertension, and diabetes. AIM: To use path analysis to test the direct and indirect association, mediated by SMuRFs, between long-term cortisol levels measured in hair cortisol concentration (HCC) and CAD. METHODS: Hair was sampled from patients admitted with acute myocardial infarction (n = 203) and a population-based sample without a diagnosis or symptoms of CAD (n = 3,134). The HCC was analyzed using radioimmunoassay and all the participants reported whether they were diagnosed with or treated for diabetes, hypertension, and hyperlipidemia. Path analysis was used to test to what degree the association between logarithmized (ln) HCC and CAD was direct or indirect, mediated by SMuRFs. RESULTS: Participants with CAD had elevated HCC compared to those without elevated HCC [median interquartile range (IQR): 75.2 (167.1) vs. 23.6 (35.0) pg/mg, p < 0.0001]. Higher HCC was associated with diabetes, hypertension, and hyperlipidemia, which, in turn, were associated with CAD. In path models, 80% of the association between ln(HCC) and CAD were mediated by SMuRFs, while the direct path between ln(HCC) and CAD was not statistically significant. CONCLUSION: The SMuRFs diabetes, hyperlipidemia, and hypertension mediate the association between ln(HCC) and CAD. Some association between ln(HCC) and CAD did not operate via the SMuRFs considered and might have a pathway through atherosclerosis or inflammation.

Identification of citrus immune regulators involved in defence against Huanglongbing using a new functional screening system.

Huanglongbing (HLB) is the most devastating citrus disease in the world. Almost all commercial citrus varieties are susceptible to the causal bacterium, Candidatus Liberibacter asiaticus (CLas), which is transmitted by the Asian citrus psyllid (ACP). Currently, there are no effective management strategies to control HLB. HLB-tolerant traits have been reported in some citrus relatives and citrus hybrids, which offer a direct pathway for discovering natural defence regulators to combat HLB. Through comparative analysis of small RNA profiles and target gene expression between an HLB-tolerant citrus hybrid (Poncirus trifoliata × Citrus reticulata) and a susceptible citrus variety, we identified a panel of candidate defence regulators for HLB-tolerance. These regulators display similar expression patterns in another HLB-tolerant citrus relative, with a distinct genetic and geographic background, the Sydney hybrid (Microcitrus virgata). Because the functional validation of candidate regulators in tree crops is always challenging, we developed a novel rapid functional screening method, using a C. Liberibacter solanacearum (CLso)/potato psyllid/Nicotiana benthamiana interaction system to mimic the natural transmission and infection circuit of the HLB complex. When combined with efficient virus-induced gene silencing in N. benthamiana, this innovative and cost-effective screening method allows for rapid identification and functional characterization of regulators involved in plant immune responses against HLB, such as the positive regulator BRCA1-Associated Protein, and the negative regulator Vascular Associated Death Protein.

Restarting training and examinations in the era of COVID-19: a perspective from the Federation of Royal Colleges of Physicians UK.

COVID-19 has proven to be a potent disruptor of postgraduate training, assessment and learning. In so doing, it has equally proved to be a potent catalyst and has driven innovation. Here we discuss the response of the Federation of the three UK Royal Colleges of Physicians to the challenges presented in these areas by the COVID-19 pandemic.

Predicting the development of overweight and obesity in children between 2.5 and 8 years of age: The prospective ABIS study.

BACKGROUND: A relationship between overweight and obesity early in life and adolescence has been reported. The aim of this study was to track changes in overweight/obesity in children and to assess risk factors related to the persistence of overweight/obesity between 2.5 and 8 years. STUDY DESIGN: Children who participated in all three follow-ups at 2.5, 5 and 8 years in the prospective cohort All Children in Southeast Sweden (ABIS) (N = 2245, 52.1% boys and 47.9% girls) were classified as underweight, normal, overweight or with obesity, and changes within categories with age were related to risk factors for development of obesity in a multivariate analysis. RESULTS: The prevalence of overweight and obesity between 2.5 and 8 years was 11%-12% and 2%-3%, respectively. Children with normal weight remained in the same category over the years, 86% between 2.5 to 5 years and 87% between 5 and 8 years. Overweight and obesity at 5 and 8 years were positively related to each other (p < 0.0001 for both). High level of TV watching at 8 years and high maternal body mass index (BMI) when the child was 5 years were related to lower probability to a normalized ISO-BMI between 5 and 8 years of age (p < 0.05 for both). CONCLUSION: Children with ISO-BMI 18.5 to 24.9 remain in that range during the first 8 years of life. Children with overweight early in life gain weight and develop obesity, and children with obesity tend to remain with obesity up to 8 years of age. TV watching and high maternal BMI were related to lower probability to weight normalization between 5 and 8 years of age. A multidisciplinary approach to promote dietary and physical activity changes in the entire family should be used for the treatment and prevention of overweight and obesity in early childhood.