Six-Food Elimination Diet Is Less Effective During Pollen Season in Adults With Eosinophilic Esophagitis Sensitized to Pollens.

INTRODUCTION: The role of inhaled and swallowed aeroallergens in treatment outcomes of adult patients with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of the 6-food elimination diet (SFED) in EoE. METHODS: We compared outcomes of patients with EoE who underwent SFED during vs outside of the pollen season. Consecutive adult patients with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Individual pollen sensitization and pollen count data were analyzed to define whether each patient had been assessed during or outside of the pollen season after SFED. All patients had active EoE (≥15 eosinophils/high-power field) before SFED and adhered to the diet under the supervision of a dietitian. RESULTS: Fifty-eight patients were included, 62.0% had positive SPT for birch and/or grass, whereas 37.9% had negative SPT. Overall, SFED response was 56.9% (95% confidence interval, 44.1%-68.8%). When stratifying response according to whether the assessment had been performed during or outside of the pollen season, patients sensitized to pollens showed significantly lower response to SFED during compared with outside of the pollen season (21.4% vs 77.3%; P = 0.003). In addition, during the pollen season, patients with pollen sensitization had significantly lower response to SFED compared with those without sensitization (21.4% vs 77.8%; P = 0.01). DISCUSSION: Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. The SPT for pollens may identify patients less likely to respond to the diet during the pollen season.

Cognitive predictors of children's arithmetic principle understanding.

The understanding of arithmetic principles (APs) is an important component of our conceptual mathematical knowledge, but we have limited knowledge about how children acquire APs. The current study examined this issue through a longitudinal study with 273 Chinese fourth graders. These children were assessed on various cognitive capacities (e.g., verbal and visuospatial working memory, processing speed, inhibition skill, numerical magnitude representation) in Grade 4 as well as on their AP understanding using multifaceted assessment and their arithmetic competence in Grade 5. Results from structural equation modeling suggested that verbal memory and inhibition skill directly predicted AP understanding, which in turn predicted arithmetic competence. Visuospatial working memory predicted AP understanding through numerical magnitude representation. The findings allow researchers to better account for the individual differences in AP understanding.

VirA+EmiC project: Evaluating real-world effectiveness and sustainability of integrated routine opportunistic hepatitis B and C testing in a large urban emergency department.

Innovative testing approaches and care pathways are required to meet global hepatitis B virus (HBV) and hepatitis C virus (HCV) elimination goals. Routine blood-borne virus (BBV) testing in emergency departments (EDs) in high-prevalence areas is suggested by the European Centre for Disease Prevention and Control (ECDC) but there is limited evidence for this. Universal HIV testing in our ED according to UK guidance has been operational since 2015. We conducted a real-world service evaluation of a modified electronic patient record (EPR) system to include opportunistic opt-out HBV/reflex-HCV tests for any routine blood test orders for ED attendees aged ≥16 years. Reactive laboratory results were communicated directly to specialist clinical teams. Our model for contacting patients requiring linkage to care (new diagnoses/known but disengaged) evolved from initially primarily hospital-led to collaborating with regional health and community service networks. Over 11 months, 81,088 patients attended the ED; 36,865 (45.5%) had a blood test. Overall uptake for both HBV and HCV testing was 75%. Seroprevalence was 0.9% for hepatitis B surface antigen (HBsAg) and 0.9% for HCV antigen (HCV-Ag). 79% of 140 successfully contacted HBsAg+patients required linkage to care, of which 87% engaged. 76% of 130 contactable HCV-Ag+patients required linkage, 52% engaged. Our results demonstrate effectiveness and sustainability of universal ED EPR opt-out HBV/HCV testing combined with comprehensive linkage to care pathways, allowing care provision particularly for marginalized at-risk groups with limited healthcare access. The findings support the ECDC BBV testing guidance and may inform future UK hepatitis testing guidance.

Validation of the Lyon classification for GORD diagnosis: acid exposure time assessed by prolonged wireless pH monitoring in healthy controls and patients with erosive oesophagitis.

OBJECTIVE: Acid exposure time (AET) from ambulatory pH studies and reflux oesophagitis are independent measurements used by the Lyon classification to diagnose GORD. This study aimed to validate AET reference ranges and diagnostic thresholds by analysis of 96-hour wireless pH studies from healthy, asymptomatic controls (HCs) and patients with and without oesophagitis. DESIGN: HC and consecutive patients referred for wireless pH studies (off acid suppressants for >7 days) underwent 96-hour pH studies at two tertiary referral centres. Erosive oesophagitis was categorised by the Los Angeles (LA) classification. Linear regression and receiver operating curve (ROC) analysis were performed to define optimal diagnostic cut-offs. RESULTS: Prolonged, 96-hour pH studies were completed in 39 HCs (age 28 (18-53) years, 72% female) and 944 patients (age 46 (16-85) years, 65% female), of whom 136 (14.5%) had reflux oesophagitis. Median AET in HC was 1.3% (upper 95th percentile 4.6%) for any study day and 2.6% (upper 95th percentile 6.9%) for the worst day (24-hour period) during the study. ROC analysis for average AET differentiated HC from patients with moderate-to-severe oesophagitis (LA BCD; sensitivity 87%, specificity 95%, positive predictive value (PPV) 59%, negative predictive value 99% for a cut-off AET of 4.3%; area under the receiver operating curve 0.95). Specificity was higher, but PPV was substantially lower for severe oesophagitis (LA CD). 'Worst-day' analysis provided similar results; however, day-to-day variability was high. CONCLUSION: Diagnostic thresholds for average AET were identified that accurately discriminate between HCs and patients with erosive oesophagitis. The findings provide conditional support for diagnostic criteria for GORD proposed by the Lyon Consensus.

Multifaceted assessment of children's inversion understanding.

The current study was aimed at examining various theoretical issues concerning children's inversion understanding (i.e., its factor structure, development, and relation with mathematics achievement) using a multifaceted assessment. A sample of 110 fourth to sixth graders was evaluated in three different measures of inversion understanding: evaluation of examples, explicit recognition, and application of procedures. The participants were also evaluated on their mathematics achievement. A one-factor structure best explains inversion understanding involving different arithmetic operations. Grade-related improvements were observed in some facets of inversion understanding. Latent profile analysis using the three inversion measures revealed seven classes of children with different inversion profiles. Furthermore, classes with better inversion understanding also had higher mathematics achievers. The current findings provide evidence to support the multifaceted nature of inversion understanding, grade-related improvements in children's inversion understanding as well as the relation between inversion understanding and mathematics achievement.

An Evaluation for the Causes of Reduced Hb A2 and the Molecular Characterization of HBD Variants in Hong Kong.

Prenatal screening of ß-thalassemia (ß-thal) carriers is based on the hallmark phenotype of microcytosis and raised Hb A2. The unanticipated birth of ß-thal major (ß-TM) offspring to ß-thal carriers who were misdiagnosed during prenatal screening have been reported. A subset of these resulted from the masked phenotype due to the coinheritance of HBD variants. In a broader sense, the causes of reduced Hb A2 in thalassemia screening, the prevalence and spectrum of HBD variants in Hong Kong remain to be characterized. Over a 13-month period, a total of 2982 samples were referred for thalassemia screening. Surplus samples with reduced Hb A2 levels (2.0%) were evaluated. HBD variations were assessed by direct sequencing. Sixty-six samples were tested. Hb H disease, HBD variants, α-thalassemia (α-thal) trait and iron deficiency were detected in 40 (60.6%), 12 (18.2%), eight (12.1%) and seven (10.6%) samples, respectively. Seven samples carried more than one of the mentioned conditions. The cause remained elusive in seven samples. Thirteen HBD variants were detected and two were recurrent, including HBD: c.-127T>C [-77 (T>C)] and HBD: c.314G>A (Hb Chori-Burnaby). A novel nonsense variant HBD: c.262C>T [codon 87 (C>T)] was detected in cis with HBD: c.-127T>C. Overall, the prevalence of HBD variants was 0.4%. This study advanced our understanding of the causes of reduced Hb A2 in clinical practice and identified hereditary disorders of α- and δ-globin genes as the prevailing causes. It established the landscape of HBD variations in our locality and highlighted the pitfall of phenotypic screening of ß-thal carriers.

An Economic Evaluation of the Cost-Effectiveness of Opt-Out Hepatitis B and Hepatitis C Testing in an Emergency Department Setting in the United Kingdom.

OBJECTIVES: The prevalence of hepatitis is high in emergency department (ED) attendees in the United Kingdom, with a prevalence of up to 2% for hepatitis B (HBV) HBsAg, and 2.9% for hepatitis C (HCV) RNA. The aim of this paper is to perform an economic evaluation of opt-out ED-based HCV and HBV testing. METHODS: A Markov model was developed to analyze the cost-effectiveness of opt-out HCV and HBV testing in EDs in the UK. The model used data from UK studies of ED testing to parameterize the HCV and HBV prevalence (1.4% HCV RNA, 0.84% HBsAg), test costs, and intervention effects (contact rates and linkage to care). For HCV, we used an antibody test cost of £3.64 and RNA test cost of £68.38, and assumed direct-acting antiviral treatment costs of £10 000. For HBV, we used a combined HBsAg and confirmatory test cost of £5.79. We also modeled the minimum prevalence of HCV (RNA-positive) and HBV (HBsAg) required to make ED testing cost-effective at a £20 000 willingness to pay per quality-adjusted life-year threshold. RESULTS: In the base case, ED testing was highly cost-effective, with HCV and HBV testing costing £8019 and £9858 per quality-adjusted life-year gained, respectively. HCV and HBV ED testing remained cost-effective at 0.25% HCV RNA or HBsAg prevalence or higher. CONCLUSIONS: Emergency department testing for HCV and HBV is highly likely to be cost-effective in many areas across the UK depending on their prevalence. Ongoing studies will help evaluate ED testing across different regions to inform testing guidelines.

The association between visual attention and arithmetic competence: The mediating role of enumeration.

The current study aimed at clarifying the nature of relation between visual attention and arithmetic competence. A group of 301 Chinese second graders was assessed. Children's visual attention was measured using two versions of a visual search task, with efficient visual search (the similarity between the target and the distractors is low) tapping automatic, stimulus-driven visual attention and inefficient visual search (the similarity between the target and the distractors is high) tapping effortful, goal-directed visual attention. Children's arithmetic competence, enumeration skills (assessed in about half of the participants), and other domain-general cognitive abilities were also assessed. The results suggest that only inefficient visual search significantly predicted children's arithmetic competence, and such a relation was mediated through their enumeration skills. The findings highlight the role of fundamental cognitive capacities in mathematics learning and provide insights into potential interventions for improving children's arithmetic competence.

Habits and Attitudes of Video Gaming and Information Technology Use in People with Schizophrenia: Cross-Sectional Survey.

BACKGROUND: Information technology and video gaming have potential advantages in the treatment of schizophrenia. However, information regarding the habits and attitudes related to internet use and video gaming in people with schizophrenia is limited. OBJECTIVE: The aim of this study was to explore the habits and attitudes regarding video gaming and information technology usage and their associated factors in people with schizophrenia in Hong Kong. METHODS: In this cross-sectional survey, service users with schizophrenia were recruited from 6 halfway hostels and 7 integrated centers for mental wellness in Hong Kong. A 79-item self-report questionnaire was utilized to explore the habits of internet use and video gaming in these people with schizophrenia. The attitude toward video gaming was assessed using the Gaming Attitudes, Motivations, and Experiences Scales. Of the 148 individuals in a convenience sample who were invited to participate in this study, 110 willingly participated (a response rate of 74.3%). The data were analyzed using descriptive statistics, a two-tailed independent t test, Pearson correlation, and principal analysis with 3 methods of rotation (varimax, equimax, and promax). RESULTS: Most participants (100/110, 90.9%) had access to the internet and half of them (54/110, 49.1%) used the internet daily mostly to watch videos (66/110, 60.0%) or read news or books, etc (42/110, 38.2%). One-third of the participants (36/110, 32.7%) used the internet to play web-based games, and most of them (88/110, 80.0%) had played a video game in the past year. The most favorable gaming platforms were cellular phones (43/88, 49%) followed by computers (19/88, 22%) and arcade cabinets (6/88, 7%). The most favorable game genre was action games (34/145, 23.4%). Those who had a bachelor's degree or higher scored lower in social interaction than those with a lower education level (P=.03). Those who played video games daily scored higher in the category of story than those who did not play daily (t86=2.03, P=.05). The most popular gaming category was autonomy and the least popular categories were violent catharsis and violent reward. Two motives, "social playing" and "evasive playing," were formed to describe the characteristics of playing video games. CONCLUSIONS: Our data showed a high internet utilization rate among people with schizophrenia in Hong Kong. Only a few of them used the internet to search for health-related information. Our study also exemplified the unique habits of gaming among the participants. Health care professionals could utilize video games to engage people with schizophrenia and promote coping with stress and provide social skills training to such people with schizophrenia. Identification of the gaming attitudes can contribute to the development of serious games for the schizophrenic population. Further investigation is vital for the promotion of mental health through web-based platforms.

Measurement of Salivary Pepsin to Detect Gastroesophageal Reflux Disease Is Not Ready for Clinical Application.

A noninvasive test for gastroesophageal reflux disease (GERD) is desirable for adults and children. Salivary pepsin measurement has been proposed as such a test.1-3 A previous study from our group demonstrated that a maximal salivary pepsin cutoff of >210 ng/mL using the PepTest device (RD Biomed, Hull, United Kingdom) had excellent specificity of 96% but modest sensitivity of 44% to diagnose GERD,4 leading to optimism about its potential use. In this study, we aimed to confirm the previously reported sensitivity and specificity in healthy volunteers and patients with heartburn, evaluate the association between a positive PepTest and response to proton pump inhibitor (PPI) therapy, assess if test-sensitivity can be improved for GERD when samples are taken over a 72-hour sampling period, and establish normal values of salivary pepsin in infants.

An Intact ACTH LC-MS/MS Assay as an Arbiter of Clinically Discordant Immunoassay Results.

BACKGROUND: Measurement of plasma adrenocorticotropic hormone (ACTH) is key in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. Two-site sandwich immunoassays dominate clinical testing of ACTH in North America; however, discordant results between manufacturers have been repeatedly reported. To resolve the discrepancy, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the intended measurand, biologically active intact ACTH (iACTH). METHODS: The multiple reaction monitoring LC-MS/MS assay was designed to selectively measure full-length iACTH, as well as ACTH analogs and fragments (i.e., ACTH1-24 and ACTH18-39). Epitope assignment of the Roche Elecsys antibodies was performed by MALDI-TOF mass spectrometry. A method comparison between Roche Elecsys and Siemens Immulite ACTH immunoassays was performed and clinically concordant/discordant results identified. In a subset of these samples, the iACTH concentration was determined using the LC-MS/MS method. RESULTS: The lower limit of the measuring interval of the iACTH LC-MS/MS assay was 9 pg/mL (2 pmol/L). The assay was linear from 9 to 1938 pg/mL (2 to 427 pmol/L). Epitope mapping revealed that the Roche capture and detection antibodies bound residues 9-12 and 36-39 of ACTH, respectively. The iACTH LC-MS/MS analysis demonstrated that for discordant results between 2 immunoassays studied, only the Roche results were highly positively correlated with the iACTH concentration. CONCLUSIONS: Immunoprecipitation of biologically active ACTH molecules followed by LC-MS/MS analysis enabled selective detection of iACTH and relevant biologically active fragments in plasma. Applied to the investigation of clinically discrepant results, this method can act as an arbiter of the concentration of iACTH present.

RUNX1 upregulation via disruption of long-range transcriptional control by a novel t(5;21)(q13;q22) translocation in acute myeloid leukemia.

RUNX1 encodes a Runt-related transcription factor that is critical for hematopoiesis. In this study, through a combinatorial molecular approach, we characterized a novel t(5;21)(q13;q22) translocation involving RUNX1 that was acquired during the progression of myelodysplastic syndrome to acute myeloid leukemia (AML) in a pediatric patient. We found that this translocation did not generate RUNX1 fusion but aberrantly upregulated RUNX1. This upregulation was attributed to the disruption of long-range chromatin interactions between the RUNX1 P2 promoter and a silencer in the first intron of the gene. Characterization of the silencer revealed a role of SNAG repressors and their corepressor LSD1/KDM1A in mediating the effect. Our findings suggest that chromosomal rearrangements may activate RUNX1 by perturbing its transcriptional control to contribute to AML pathogenesis, in keeping with an emerging oncogenic role of RUNX1 in leukemia.

Is conditional reasoning related to mathematical problem solving?

The current study aimed to investigate the relation between conditional reasoning, which is a common type of logical reasoning, and children's mathematical problem solving. A sample of 124 fourth graders was tested for their conditional reasoning skills and their mathematical problem solving skills, as well as a list of control variables (e.g., IQ, working memory, reading) and potential mediators (number sentence construction and computation). The children's ability to make modus ponens (MP) inferences significantly predicted their mathematical problem solving skills, even after controlling for the potential confounding variables. The relation was mediated by the number sentence construction skills. The findings, in addition to supporting the link between conditional reasoning and mathematics, further indicate that the ability to process relations may be the mechanism underlying the relation. Theoretical and practical implications are discussed.

The unique and shared contributions of arithmetic operation understanding and numerical magnitude representation to children's mathematics achievement.

The current study examined the unique and shared contributions of arithmetic operation understanding and numerical magnitude representation to children's mathematics achievement. A sample of 124 fourth graders was tested on their arithmetic operation understanding (as reflected by their understanding of arithmetic principles and the knowledge about the application of arithmetic operations) and their precision of rational number magnitude representation. They were also tested on their mathematics achievement and arithmetic computation performance as well as the potential confounding factors. The findings suggested that both arithmetic operation understanding and numerical magnitude representation uniquely predicted children's mathematics achievement. The findings highlight the significance of arithmetic operation understanding in mathematics learning.

Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia.

Helicase-like transcription factor is a SWI/SNF chromatin remodeling factor involved in various biological processes. However, little is known about its role in hematopoiesis. In this study, we measured helicase-like transcription factor mRNA expression in the bone marrow of 204 adult patients with de novo acute myeloid leukemia. Patients were dichotomized into low and high expression groups at the median level for clinicopathological correlations. Helicase-like transcription factor levels were dramatically reduced in the low expression patient group compared to those in the normal controls (n=40) (P<0.0001). Low helicase-like transcription factor expression correlated positively with French-American-British M4/M5 subtypes (P<0.0001) and complex cytogenetic abnormalities (P=0.02 for ≥3 abnormalities;P=0.004 for ≥5 abnormalities) but negatively with CEBPA double mutations (P=0.012). Also, low expression correlated with poorer overall (P=0.005) and event-free (P=0.006) survival in the intermediate-risk cytogenetic subgroup. Consistent with the more aggressive disease associated with low expression, helicase-like transcription factor knockdown in leukemic cells promoted proliferation and chromosomal instability that was accompanied by downregulation of mitotic regulators and impaired DNA damage response. The significance of helicase-like transcription factor in genome maintenance was further indicated by its markedly elevated expression in normal human CD34(+)hematopoietic stem cells. We further demonstrated that helicase-like transcription factor was a RUNX1 target and transcriptionally repressed by RUNX1-ETO and site-specific DNA methylation through a duplicated RUNX1 binding site in its promoter. Taken together, our findings provide new mechanistic insights on genomic instability linked to helicase-like transcription factor deregulation, and strongly suggest a tumor suppressor function of the SWI/SNF protein in acute myeloid leukemia.

The underlying number-space mapping among kindergarteners and its relation with early numerical abilities.

People map numbers onto space. The well-replicated SNARC (spatial-numerical association of response codes) effect indicates that people have a left-sided bias when responding to small numbers and a right-sided bias when responding to large numbers. This study examined whether such spatial codes were tagged to the ordinal or magnitude information of numbers among kindergarteners and whether it was related to early numerical abilities. Based on the traditional magnitude judgment task, we developed two variant tasks-namely the month judgment task and dot judgment task-to elicit ordinal and magnitude processing of numbers, respectively. Results showed that kindergarteners oriented small numbers toward the left side and large numbers toward the right side when processing the ordinal information of numbers in the month judgment task but not when processing the magnitude information in the number judgment task and dot judgment task, suggesting that the left-to-right spatial bias was probably tagged to the ordinal but not magnitude property of numbers. Moreover, the strength of the SNARC effect was not related to early numerical abilities. These findings have important implications for the early spatial representation of numbers and its role in numerical performance among kindergarteners.

Eosinophilic oesophagitis: investigations and management.

Eosinophilic oesophagitis (EO) is an immune/antigen mediated, chronic, relapsing disease characterised by dysphagia, food bolus impaction and a dense oesophageal eosinophilic infiltrate. Characteristic endoscopic features include corrugated rings, linear furrows and white exudates, but none are diagnostic. Despite its increasing prevalence, EO remains underdiagnosed. There is a strong association with other atopic conditions. Symptoms, histology and endoscopic findings can overlap with gastro-oesophageal reflux disease. Currently endoscopy and oesophageal biopsies are the investigation of choice. Oesophageal physiology studies, endoscopic ultrasound, impedance planimetry and serology may have a role in the diagnosis and monitoring of response to therapy. Acid reducing medication is advocated as first line or adjuvant therapy. Dietary therapy is comprised of elimination diets or can be guided by allergen assessment. In adults, topical corticosteroids are the mainstay of therapy. Endoscopic dilatation is safe and effective for the treatment of non-responsive strictures. Other therapeutic options (immunomodulators, biological agents, leukotriene receptor antagonists) are under investigation.