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BACKGROUND: Sliding hiatal herniation (SHH) and gastroesophageal reflux (GER) commonly occur in French bulldogs. Wireless pH monitoring can quantitatively assess acidic GER in dogs affected by SHH. HYPOTHESIS/OBJECTIVES: Measure acidic GER in French bulldogs with SHH, pre- and post-brachycephalic obstructive airway syndrome (BOAS) surgery, utilizing a wireless pH capsule (Bravo Calibration-free, Medtronic, Minnesota), and correlate with owners observations of regurgitation. ANIMALS: Eleven French bulldogs diagnosed with SHH via swallowing fluoroscopy. METHODS: Prospective cohort study. A pH capsule was endoscopically placed in the esophagus. Up to 96 hours of data were acquired as the owner logged clinical signs. Spearmans correlation and Wilcoxon rank-sum tests evaluated factors correlated with acid exposure time (AET), defined by the % time pH

Abstract Background/aims Crohn’s disease (CD) and intestinal tuberculosis (ITB) are gastrointestinal (GI) inflammatory disorders with overlapping clinical presentations but diverging etiologies. The study aims to decipher CD and ITB-associated gut dysbiosis signatures and identify disease-associated co-occurring modules to evaluate whether this dysbiosis signature is a disease-specific trait or is a shared feature across diseases of diverging etiologies. Methods Disease-associated gut microbial modules were identified using statistical machine learning and co-abundance network analysis in controls, CD and ITB patients recruited as part of this study. Module reproducibility was reinvestigated through meta-network analysis encompassing >5400 bacteriomes and ~900 mycobiomes. Subsequently, >1600 Indian gut microbiomes were analyzed to identify a central-core gut microbiome of 46 taxa, whose abundances aided in the formulation of an India-specific Core Gut Microbiome Score (CGMS) to measure the degree of core retention. Results Both diseases witness similar patterns of alterations in [alpha]-diversity, characterized by a significant reduction in gut bacterial (i.e., bacterial/archaeal) diversity and a concomitant increase in the fungal [alpha]-diversity. Specific bacterial taxa, along with the diverging mycobiome enabled distinction between the diseases. Co-abundance network analysis of these taxa, validated by integrated meta-network analysis, revealed a ‘disease-depleted’ module, consistent across multiple cohorts, with >75% of this module constituting the central-core Indian gut microbiome. CGMS robustly assessed the core-microbiome loss across different stages of gut inflammatory disorders, in Indian and international cohorts. Conclusions While the disease-specific gain of detrimental bacteria forms an important component of gut dysbiosis, loss of the core microbiome is a shared phenomenon contributing to various GI disorders.

OBJECTIVES: The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats. METHODS: Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines. RESULTS: Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation. CONCLUSIONS AND RELEVANCE: When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.

Zinc is an essential micronutrient that promotes normal growth, development and immune function. In the context of persistent dietary zinc inadequacies, large-scale food fortification can help fill the gap between intake and requirements. Burkina Faso mandates wheat flour fortification with iron and folic acid. We used activity-based cost modelling to estimate the cost of adding zinc to the country's wheat flour fortification standard assuming (1) no change in compliance with the national standard, and (2) a substantial improvement in compliance. We used household food consumption data to model effective coverage, that is, the number of women of reproductive age (WRA) predicted to achieve adequate zinc density (zinc intake/1000 kcal) with the addition of fortification to diets. Without interventions, the prevalence of inadequate dietary zinc density was ~35.5%. With no change in compliance, the annual average incremental cost of adding zinc to fortified wheat flour was $10,347, which would effectively cover

We explore the performance of a recently introduced N5-scaling excited-state-specific second order perturbation theory (ESMP2) on the singlet excitations of the Thiel benchmarking set. We find that, without regularization, ESMP2 is quite sensitive to π system size, performing well in molecules with small π systems but poorly in those with larger π systems. With regularization, ESMP2 is far less sensitive to π system size and shows a higher overall accuracy on the Thiel set than CC2, equation of motion-coupled cluster with singles and doubles, CC3, and a wide variety of time-dependent density functional approaches. Unsurprisingly, even regularized ESMP2 is less accurate than multi-reference perturbation theory on this test set, which can, in part, be explained by the set's inclusion of some doubly excited states but none of the strong charge transfer states that often pose challenges for state-averaging. Beyond energetics, we find that the ESMP2 doubles norm offers a relatively low-cost way to test for doubly excited character without the need to define an active space.

Introduction Micronutrient deficiencies are common among women of reproductive age (WRA) and children in Senegal. Large-scale food fortification (LSFF) can help fill gaps in dietary intake.Methods We used household food consumption data to model the contributions of existing LSFF programmes (vitamin A-fortified refined oil and iron and folic acid-fortified wheat flour) and the potential contributions of expanding these programmes to meeting the micronutrient requirements of WRA (15–49 7 years) and children (6–59 months).Results Without fortification, apparent inadequacy of household diets for meeting micronutrient requirements exceeded 70% for vitamin A, thiamin, riboflavin, folate and zinc, was 61% for iron among WRA (43% among children) and was ~25% for vitamin B12. At estimated current compliance, fortified refined oil was predicted to reduce vitamin A inadequacy to ~35% and could further reduce inadequacy to ~25% if compliance with the standard improved. Fortified wheat flour at estimated current compliance reduced iron and, especially, folate inadequacy, but improvements in compliance would be necessary to achieve the full potential. Beyond existing programmes, expanding wheat flour fortification to include additional micronutrients was predicted to have a modest impact on thiamin and riboflavin inadequacies and larger impacts on vitamin B12 and, especially, zinc inadequacies. Adding a programme to import fortified rice could further reduce inadequacies of multiple micronutrients (generally by >10 percentage points), although potential risk of high intake of vitamin A, folic acid and zinc among children should be carefully considered. With both wheat flour and rice fortification, predicted prevalence of vitamin A, iron and zinc inadequacy remained above 25% in some regions, pointing to the potential need for coordinated, targeted micronutrient interventions to fully close gaps.Conclusions When considered alongside evidence on the cost and affordability of these programmes, this evidence can help inform the development of a comprehensive micronutrient intervention strategy in Senegal.

Abstract Irritable bowel syndrome (IBS) is a prevalent disorder of gut‐brain interaction without a reliable cure. Evidence suggests that an alteration of the gut microbiome may contribute to IBS pathogenesis, motivating the development of microbiome‐targeted therapies to alleviate IBS symptoms. However, IBS‐specific microbiome signatures are variable across cohorts. A total of 9204 datasets were meta‐analyzed, derived from fourteen IBS microbiome discovery cohorts, three validation cohorts for diet‐microbiome interactions, and five rifaximin therapy cohorts. The consistent bacterial species and functional signatures associated with IBS were identified. Network analysis revealed two distinct IBS‐enriched microbiota clusters; obligate anaerobes that are found commonly in the gut, and facultative anaerobes typically present in the mouth, implying a possible association between oral bacterial translocation to gut and IBS pathogenesis. By analyzing diet‐microbiome interactions, microbiota‐targeted diets that can potentially modulate the altered gut microbiota of IBS subjects toward a healthy status were identified. Furthermore, rifaximin treatment of IBS subjects was linked with a reduction in the abundance of facultatively anaerobic pathobionts. Gut microbiome signatures were identified across IBS cohorts that may inform the development of therapies for microbiome modulation in IBS. The microbiota‐targeted diet patterns described may enable nutritional intervention trials in IBS and for assisting dietary management.

BackgroundSerum folate is considered a biomarker of chronic enteropathy (CE) in dogs, but few studies have examined associations with markers of CE.Hypothesis/objectivesTo evaluate serum folate concentrations in dogs with and without CE and associations with sample hemolysis and selected markers of CE. We hypothesized that hypofolatemia would be more common in dogs with CE and associated with hypocobalaminemia, higher CIBDAI, and hypoalbuminemia.AnimalsSix hundred seventy-three dogs with available serum folate measurements performed at an academic veterinary hospital between January 2016 and December 2019.MethodsMedical records were retrospectively reviewed to categorize cases as CE or non-CE and record clinical details and laboratory markers. Relationships between serum folate, cobalamin, and CE variables were assessed using chi-square, Kruskal-Wallis, or Spearman's correlation tests.ResultsOf the 673 dogs, 99 CE were compared to 95 non-CE. In the overall cohort, serum folate concentration did not correlate with sample hemolysis (P = .75). In the CE subset, serum folate and cobalamin concentrations were positively associated (rho = 0.34, FDR = 0.02). However, serum folate concentrations (median [25th, 75th percentiles]) were higher (CE: 12.1 (8.9, 16.1), non-CE: 10.4 (7.2, 15.5); P = .04) and cobalamin concentrations were lower (CE: 343 (240, 597), non-CE: 550 (329, 749); P = .001) in the CE vs non-CE group. Serum folate was not associated with markers of CE, but serum cobalamin was associated with albumin (P = .04) and cholesterol (P = .03).Conclusions and clinical importanceHypofolatemia is an inferior biomarker of CE compared to hypocobalaminemia.

Abstract Background Sliding hiatal herniation (SHH) and gastroesophageal reflux (GER) commonly occur in French bulldogs. Wireless pH monitoring can quantitatively assess acidic GER in dogs affected by SHH. Hypothesis/Objectives Measure acidic GER in French bulldogs with SHH, pre‐ and post‐brachycephalic obstructive airway syndrome (BOAS) surgery, utilizing a wireless pH capsule (Bravo Calibration‐free, Medtronic, Minnesota), and correlate with owners' observations of regurgitation. Animals Eleven French bulldogs diagnosed with SHH via swallowing fluoroscopy. Methods Prospective cohort study. A pH capsule was endoscopically placed in the esophagus. Up to 96 hours of data were acquired as the owner logged clinical signs. Spearman's correlation and Wilcoxon rank‐sum tests evaluated factors correlated with acid exposure time (AET), defined by the % time pH

The information on nutritional profile of cooked foods is important to both food manufacturers and consumers, and a major challenge to obtaining precise information is the inherent variation in composition across biological samples of any given raw ingredient. The ideal solution would address precision and generability, but the current solutions are limited in their capabilities; analytical methods are too costly to scale, retention-factor based methods are scalable but approximate, and kinetic models are bespoke to a food and nutrient. We provide an alternate solution that predicts the micronutrient profile in cooked food from the raw food composition, and for multiple foods. The prediction model is trained on an existing food composition dataset and has a 31% lower error on average (across all foods, processes and nutrients) than predictions obtained using the baseline method of retention-factors. Our results argue that data scaling and transformation prior to training the models is important to mitigate any yield bias. This study demonstrates the potential of machine learning methods over current solutions, and additionally provides guidance for the future generation of food composition data, specifically for sampling approach, data quality checks, and data representation standards.

Summary: Lung cancer varies between Caucasians and Asians. There have been differences recorded in the epidemiology, genomics, standard therapies and outcomes, with variations according to the geography and ethnicity which affect the decision for optimal treatment of the patients. To better understand the profile of lung cancer in Southeast Asia, with a focus on India, we have comprehensively reviewed the available data, and discuss the challenges and the way forward. A substantial proportion of patients with lung cancer in Southeast Asia are neversmokers, and adenocarcinoma is the common histopathologic subtype, found in approximately a third of the patients. EGFR mutations are noted in 23–30% of patients, and ALK rearrangements are noted in 5–7%. Therapies are similar to global standards, although access to newer modalities and molecules is a challenge. Collaborative research, political will with various policy changes and patient advocacy are urgently needed.

Background and Objectives: Klebsiella pneumoniae is a healthcare-associated infections agent and could be an extended spectrum β-lactamase (ESBL) producer. Understanding the transmission of this bacterium in a hospital setting needs accurate typing methods. An antibiogram is used to detect the resistance pattern of the isolates. Random Amplified Polymorphic DNA (RAPD) and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR are rapid, technically simple, and easy-to-interpret DNA typing methods. This study aimed to evaluate the use of antibiotyping, RAPD-, and ERIC-PCR to investigate the heterogeneity of K. pneumoniae isolated from clinical specimens. Materials and Methods: The antibiograms of 46 K. pneumoniae clinical isolates were determined by Vitek® 2 Compact. All isolates underwent RAPD-PCR using AP4 primer and ERIC-PCR using ERIC-2 primer. The dendrogram was generated using the GelJ software and analyzed to determine its similarity. The analysis of antibiogram and the molecular typing diversity index was calculated using the formula of the Simpson’s diversity index. Results: About 71.7% of the isolates were ESBL-producers, and more than 80% of isolates were susceptible to amikacin, ertapenem, and meropenem. The antibiotyping produced 32 diverse types with DI = 0.964. In Conclusion: Antibiotyping, RAPD- and ERIC-PCR showed powerful discrimination power among the isolates, supported the diversity of K. pneumoniae isolates in current study. These combination could be promising tools for clonal relationship determination, including in tracking the transmission of the outbreak’s agent in hospital setting.

During the COVID-19 pandemic, several forecasting models were released to predict the spread of the virus along variables vital for public health policymaking. Of these, the susceptible–infected–recovered (SIR) compartmental model was the most common. In this paper, we investigated the forecasting performance of The University of Texas COVID-19 Modeling Consortium SIR model. We considered the following daily outcomes: hospitalizations, ICU patients, and deaths. We evaluated the overall forecasting performance, highlighted some stark forecast biases, and considered forecast errors conditional on different pandemic regimes. We found that this model tends to overforecast over the longer horizons and when there is a surge in viral spread. We bolstered these findings by linking them to faults with the SIR framework itself.

In this article, we present the first results of the project OPEN-MATH. The research project aims at acknowledging the need for learning environments with differentiation strategies for all. We developed a model for inclusive mathematics learning, based on the Theory of Objectification and a broad idea of differentiation realized through Open Learning. It poses an interdisciplinary research issue that requires the collaboration of two sub-disciplines pertaining to the area of educational studies: Inclusive Education and Mathematics Education. The results we present here are related to the dialogue between theory and practice, whose outcome is a teaching and learning model for inclusion in mathematics. The construction of the teaching and learning model moves along two complementary paths: (1) concerning the theoretical point of view, we implemented connecting theory strategies to network Open Education and the Theory of Objectification; and (2) concerning the methodological point of view, we implemented Educational Design Research. The new teaching-learning model is the result of theoretical and methodological validation in real contexts according to an interdisciplinary approach. This study shows the strengths of interdisciplinary research for the pursuit of inclusive mathematics and high standards of learning.

Klebsiella pneumoniae bacteremia is one of the leading causes of sepsis that has a high mortality rate. The effect of multidrug resistance and different virulence of Klebsiella pneumoniae on mortality is still controversial. This study aimed to determine the impact of hypervirulent K. pneumoniae (hvKp), MDR, and clinical characteristics on mortality of K. pneumoniae bacteremia patients. A retrospective cross-sectional study was conducted on K. pneumoniae bacteremia cases of patients hospitalized at Professor dr. I.G.N.G Ngoerah General Hospital from December 1, 2020, to May 31, 2021. A positive PCR of rmpA, iucA genes, and/or a positive string test was identified as hvKp. The mortality rate of 51 K. pneumoniae bacteremia patients samples (aged 0-74 years) was 72.5%, in which 9.8% (5/51) of them were hvKp and 51% of the isolates (26/51) produced the Extended Spectrum Beta Lactamase (ESBL). Furthermore, 9.8% (5/51) of the cases were carbapenem-resistant. Thus, hvKp, MDR, gender characteristics, and comorbidities do not significantly affect the mortality of K. pneumoniae bacteremia patients. Multivariate logistic regression analysis showed that sepsis (odds ratio (OR) 4.29; p=0.038) and adult age group (mean 50 years) (OR 3.75; p=0.039) are independent predictors with a significant effect on mortality of K. pneumoniae bacteremia patients. Careful and integrated management of K. pneumoniae bacteremia patients is essential for better outcomes, especially in sepsis and elderly patients. Although hvKp prevalence is low, emerging MDR-hvKp in health facilities is a severe concern for further actions and research.