Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands.

PURPOSE: The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). PARTICIPANTS: Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected. FINDINGS TO DATE: Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia. FUTURE PLANS: Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function. TRIAL REGISTRATION NUMBER: NCT04977635.

Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.

Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.

HLA genotyping in children with celiac disease allows to establish the risk of developing type 1 diabetes.

BACKGROUND AND AIMS: Celiac Disease (CD) and Type 1 Diabetes (T1D) often co-occur and share genetic components in the HLA class II region. We aimed to study the usefulness of HLA genotyping in predicting the risk of developing T1D in patients with CD and the temporal relationship between these diseases. METHODS: A cohort of 1,886 Sardinian patients, including 822 with CD, 1,064 with T1D, and 627 controls, underwent HLA class II typing. Seventy-six out of 822 CD patients were also affected by T1D (CD-T1D), and their HLA genotypes were analyzed for specific HLA associations with CD, T1D and controls. RESULTS: High-risk HLA-DQ genotypes, including HLA-DQ2.5/DQ8, -DQ2.5/DQ2.5, and -DQ2.5/DQ2.3, were strongly associated with CD-T1D with frequencies of 34.5%, 15.9%, and 18.8%, respectively. Conversely, certain HLA genotypes associated with CD appeared to confer protection against T1D development. Therefore, HLA genotyping allows the identification of those CD patients that might develop T1D. The frequency of patients with CD preceding T1D is higher in younger children than older ones, with implications for the early childhood approach to diabetes prevention. CONCLUSIONS: CD is a condition for future T1D development, and specific HLA genotypes can predict this risk. Early screening for celiac autoimmunity and subsequent HLA typing in CD children could help identify those at high risk for T1D, allowing for proactive interventions and immunotherapies to preserve beta-cell function. These findings may support the re-evaluation of HLA typing in children with CD.

Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma.

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16 mg/ml) and sonication time (5, 10, 15 min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5 mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6 months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.

Ozonation for Pseudomonas paracarnis control: biofilm removal and preservation of chicken meat during refrigerated storage.

Ozone has been studied to control microorganisms in food, as well as to control biofilm. In this context, the goals of this work were to determine the effect of ozonated water in the removal of Pseudomonas paracarnis biofilm and the effect of ozone gas and ozonated water on inactivating P. paracarnis in deboned chicken breast meat and its effect on product color. AISI 304 coupons were used as a surface for biofilm formation. The coupons were immerged into minimal medium for Pseudomonas inoculated with the P. paracarnis overnight culture (1% w/v) followed by incubation at 25 °C for 7 days. To obtain ozonized water, two different systems were used: system with microbubble generator (MB) and system with porous stone diffuser (PSD). The inlet ozone concentration was 19 mg/L and flow rate of 1 L/min. The coupons were subjected to ozonized water for 10 and 20 min. The chicken breast meat was exposed to gaseous ozone and ozonized water for 40 min. After the ozonation process, chicken meat samples were stored at 8 °C, for 5 days. More expressive removals of biofilm were obtained when using ozonized water obtained in the system with microbubble generator (MB for 20 min-reduction of 2.3 log cycles) and system with porous stone diffuser (PSD for 10 min-reduction of 2.7 log cycles; PSD for 20 min-reduction of 2.6 log cycles). The treatment of chicken meat with ozone gas resulted in lower counting of Pseudomonas, when compared with the control treatments and with ozonized water, both immediately after ozonation (day 1) and after 5 days of storage. The luminosity in the chicken meat samples treated with ozonized water was higher than that verified in the control treatments and with ozone gas, immediately after ozonation (day 1). A similar trend was observed in hue angle and color difference, in which the highest values were obtained for treatment with ozonized water. Based on the results obtained in this study, it was concluded that ozonated water can be used to remove P. paracarnis biofilm from stainless steel under static conditions and gaseous ozone is more efficient in the inactivation of P. paracarnis from chicken breast meat, when compared to ozonated water.

Lupus Podocytopathy: A Rare Cause of Nephrotic Syndrome in Patients with Systemic Lupus Erythematosus.

Lupus podocytopathy, a unique form of lupus nephritis, mimics minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and represents approximately 1% of lupus nephritis biopsies. Lupus podocytopathy is characterized by diffuse epithelial cell foot process effacement without immune complex deposition or with only mesangial immune complex deposition. We present the case of a young woman with systemic lupus erythematosus (SLE) who presented with nephrotic syndrome and acute kidney injury (AKI) and was subsequently diagnosed with lupus podocytopathy.

Toxicity of allyl isothiocyanate applied in systems with or without recirculation for controlling Sitophilus zeamais, Rhyzopertha dominica, and Tribolium castaneum in corn grains.

BACKGROUND: The application of allyl isothiocyanate (AITC) has been proposed as an alternative to control stored-grain insects. However, AITC is a compound with a low diffusion coefficient, making its distribution throughout the grain mass difficult. Therefore, the objective of the present study was to evaluate the effectiveness of AITC applied in systems with or without recirculation for controlling Sitophilus zeamais (Mots. 1855) (Coleoptera: Curculionidae), Rhyzopertha dominica (Fabr.) (Coleoptera: Bostrichidae), and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) infesting a corn grain mass. The assays used a polyvinyl chloride (PVC) prototype, dimensioned 1.60 m in length, 0.30 m in diameter, and a static capacity of 60 kg of grains. AITC toxicity to insects was evaluated at the base, 0.5 m from the base, and top of the grain column (1.0 m). Different concentrations of AITC were tested for an exposure period of 48 h. RESULTS: In the system without AITC recirculation, insect mortality was verified only at the base of the grain column. However, insect mortality was considered uniform at the different positions of the column when the AITC recirculation system was adopted. In this system, there was also a marked reduction in the instantaneous population growth rate of S. zeamais, T. castaneum, and R. dominica, and a decrease in the dry matter loss of the grains, when the AITC concentrations were increased. CONCLUSION: AITC recirculation proved to be a viable strategy for protecting grains against the species S. zeamais, R. dominica, and T. castaneum. AITC fumigation ultimately did not cause changes in grain quality. © 2023 Society of Chemical Industry.

Peripheral blood mononuclear cells reactivity in recent-onset type I diabetes patients is directed against the leader peptide of preproinsulin, GAD65271-285 and GAD65431-450.

Introduction: T cell reactivity against pancreatic autoantigens is considered one of the main contributors to the destruction of insulin-producing cells in type 1 diabetes (T1D). Over the years, peptide epitopes derived from these autoantigens have been described in NOD mice and in both HLA class II transgenic mice and humans. However, which ones are involved in the early onset or in the progressive phases of the disease is still unclear. Methods: In this work we have investigated, in early-onset T1D pediatric patients and HLA-matched controls from Sardinia, the potential of preproinsulin (PPI) and glutamate decarboxylase 65 (GAD65)-derived peptides to induce spontaneous T cell proliferation responses of peripheral blood mononuclear cells (PBMCs). Results: Significant T cell responses against PPI1-18, PPI7-19 and PPI31-49, the first two belonging to the leader sequence of PPI, and GAD65271-285 and GAD65431-450, were found in HLA-DR4, -DQ8 and -DR3, -DQ2 T1D children. Conclusions: These data show that cryptic epitopes from the leader sequence of the PPI and GAD65271-285 and GAD65431-450 peptides might be among the critical antigenic epitopes eliciting the primary autoreactive responses in the early phases of the disease. These results may have implications in the design of immunogenic PPI and GAD65 peptides for peptide-based immunotherapy.

Weight Regain After Bariatric Surgery: Scope of the Problem, Causes, Prevention, and Treatment.

PURPOSE OF REVIEW: Although bariatric surgery is the most effective treatment of severe obesity, a proportion of patients experience clinically significant weight regain (WR) with further out from surgery. The purpose of this review is to summarize the prevalence, predictors, and causes of weight regain. RECENT FINDINGS: Estimating the prevalence of WR is limited by a lack of consensus on its definition. While anatomic failures such as dilated gastric fundus after sleeve gastrectomy and gastro-gastric fistula after Roux-en-Y gastric bypass can lead to WR, the most common causes appear to be dysregulated/maladaptive eating behaviors, lifestyle factors, and physiological compensatory mechanisms. To date, dietary, supportive, behavioral, and exercise interventions have not demonstrated a clinically meaningful impact on WR, and there is limited evidence for pharmacotherapy. Future studies should be aimed at better defining WR to begin to understand the etiologies. Additionally, there is a need for non-surgical interventions with demonstrated efficacy in rigorous randomized controlled trials for the prevention and reversal of WR after bariatric surgery.

Type 1 diabetes management: Room for improvement.

AIMS/HYPOTHESIS: Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. METHODS: Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. RESULTS: Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. CONCLUSION: Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.

Synthesis of Bis(3-indolyl)methanes Mediated by Potassium tert-Butoxide.

The indole moiety is an important N-heterocycle found in natural products, and a key structural component of many value-added chemicals including pharmaceuticals. In particular, bis(3-indolyl)methanes (BIMs) are an important subgroup of indoles, composed of two indole units. Herein, we report the development of a simple method to access BIMs derivatives in yields of up to 77 % by exploiting a tBuOK-mediated coupling reaction of indoles and benzyl alcohols.

Optimizing Perioperative Fluid Management in Complex Abdominal Wall Reconstruction to Prevent Postoperative Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a serious postoperative complication of abdominal wall reconstruction that can significantly impact outcomes of these patients. This study examines AKI following abdominal wall hernia repair to determine incidence and risk factors and outline potential mitigation strategies. METHODS: Using a single institution IRB-approved prospective database, patients undergoing complex abdominal wall reconstruction from 2013 to 2021 were identified. Patients with AKI were compared to controls and preoperative and intraoperative characteristics were evaluated. Multivariate analysis was utilized to identify factors associated with development of AKI. RESULTS: 297 patients were reviewed, 21.2 % (n = 63 patients) had AKI. Patients with AKI had a greater decrease in postoperative GFR to preoperative GFR (40.5% vs 18.3%, p <0.0001). Factors associated with AKI included ASA score >2 (odds ratio (OR) = 2.10, [1.50; 5.12], p = 0.02), HTN (OR = 2.05, [1.05; 4.0], p = 0.04), higher baseline Cr (OR = 5.98, [2.56; 13.98], p <0.0001), and diabetes (OR = 0.135, [0.0275; 0.666], p = 0.01). Operative time was longer in patients who developed AKI [average 400 min (range: 278-510 min) vs 310 min (range: 260-374 min), p = 0.04] and was an independent predictor of developing AKI (OR = 319.59, [137.25; 744.65], p <0.0001). DISCUSSION: Preoperative identification of patients with medical comorbidities undergoing elective complex abdominal wall reconstruction continues to be imperative to improve outcomes. This study demonstrates that perioperative management for high risk patients requires flexibility, including potential adjustments to enhanced recovery after surgery protocols in order to adequately address the risks for AKI.

Low-pressure ozone injection system: relationship between reaction kinetics and physical properties of grains.

BACKGROUND: The ozonation of grains in a closed system at low pressure is a strategy with the potential for treating packaged products. Research is necessary to characterize the reaction kinetics of ozone in this type of injection system so that it is possible to design chambers and determine the ozone concentrations suitable for commercial-scale applications. The objective of this study was therefore to characterize the low-pressure ozone injection system in relation to the physical properties of the grains and determine possible changes in their quality. Samples (5 kg each) of common beans, cowpea beans, corn, popcorn kernels, paddy rice, and polished rice were exposed to ozone in a 70 L hypobaric chamber. Initially, the internal pressure of the chamber was reduced to 500 hPa. Then, ozone was injected at a concentration of 32.10 g m-3 at a volumetric flow rate of 1 L min-1 until reaching a pressure of 1000 hPa. To relate the decomposition of ozone to the grains that were being evaluated, different physical properties were determined, and quality analysis was conducted. RESULTS: Ozone gas half-life outside and inside the package depended on the grain type. Ozone decomposition was quickest in polished rice and slowest in common beans. The half-life of the different grains ranged from 17.8 to 52.9 and 16.4 to 52.9 min, outside and inside the package, respectively. Considering the physical properties, specific surface (Ss), surface area (SA), and sphericity (φ) exhibited a significant correlation with the decomposition rate constant (k) of ozone. However, the variables volume (V), permeability (K), porosity (ε), and specific mass (ρ) showed no correlation with k. CONCLUSION: The physical properties of grain influenced the reaction kinetics of ozone gas during the low-pressure injection process. Ozone gas injection at low pressures did not alter the quality attributes of the grains under study. © 2022 Society of Chemical Industry.

Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition.

Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia.

Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children.

Selection of Pediatric Mental Health Quality Measures for Health System Improvement in British Columbia Based on a Modified Delphi Approach.

Background: The COVID-19 pandemic has highlighted the importance of mental wellbeing. The identification and implementation of quality measures can improve health outcomes and patient experience. The objective was to identify and define a core set of valid and relevant pediatric mental health quality measures that will support health system evaluation and quality improvement in British Columbia, Canada. Methods: The study consisted of four phases. First, a comprehensive database search identified valid pediatric quality measures focused on mental health and substance use (MH/SU). Second, the identified quality measures were mapped to focus areas, which were then prioritized by two stakeholder groups consisting of 26 members. Third, up to two representative measures for each prioritized focus area were pre-selected by an expert panel (n = 9). And fourth, a three-step modified Delphi approach was employed to (1) assess each quality measure on a 7-point Likert scale against three relevance criteria (representative of a quality problem, value to intended audience and actionable), (2) discuss the results, and (3) select and rank the most relevant measures. Forty-eight stakeholders were invited to participate; of those 24 completed the round 1 survey, 21 participated in the round 2 discussion and 18 voted in the round 3 selection and ranking survey. For round 1, consensus was determined when at least 70% of the response rates were within the range of five to seven. For round 3, Kendall's coefficient of concordance W was used as an estimator of inter-rater reliability. Results: One-hundred pediatric mental health quality measures were identified in the database search. Of those, 37 were mapped to ten focus areas. Pre-selection resulted in 19 representative measures moving forward to the Delphi study. Eleven measures met the consensus thresholds and were brought forward to the round 2 discussion. Round 3 ranking showed moderate to strong raters' agreement (Kendall's W = 0.595; p < 0.01) and resulted in the following five highest-ranked measures: level of satisfaction after discharge from inpatient admission due to MH/SU, number of patients experiencing seclusion or restraint, length of time from eating disorder referral to assessment, number of ED visits due to MH/SU, and number of readmissions to ED. Conclusion: The selected core set of valid and relevant pediatric quality measures will support sustainable system change in British Columbia. The five top-ranked measures will be refined and tested for data collection feasibility before being implemented in the province.

Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters.

Hypoxia exerts profound effects on cell physiology, but its effect on colonic uptake of the microbiota-generated forms of vitamin B1 (i.e., thiamin pyrophosphate [TPP] and free thiamine) has not been described. Here, we used human colonic epithelial NCM460 cells and human differentiated colonoid monolayers as in vitro and ex vivo models, respectively, and were subjected to either chamber (1% O2, 5% CO2, and 94% N2) or chemically (desferrioxamine; 250 µM)-induced hypoxia followed by determination of different physiological-molecular parameters. We showed that hypoxia causes significant inhibition in TPP and free thiamin uptake by colonic NCM460 cells and colonoid monolayers; it also caused a significant reduction in the expression of TPP (SLC44A4) and free thiamin (SLC19A2 and SLC19A3) transporters and in activity of their gene promoters. Furthermore, hypoxia caused a significant induction in levels of hypoxia-inducible transcription factor (HIF)-1α but not HIF-2α. Knocking down HIF-1α using gene-specific siRNAs in NCM460 cells maintained under hypoxic conditions, on the other hand, led to a significant reversal in the inhibitory effect of hypoxia on TPP and free thiamin uptake as well as on the expression of their transporters. Finally, a marked reduction in level of expression of the nuclear factors cAMP responsive element-binding protein 1 and gut-enriched Krüppel-like factor 4 (required for activity of SLC44A4 and SLC19A2 promoters, respectively) was observed under hypoxic conditions. In summary, hypoxia causes severe inhibition in colonic TPP and free thiamin uptake that is mediated at least in part via HIF-1α-mediated transcriptional mechanisms affecting their respective transporters.

Antibacterial and anti-inflammatory effects of Lactobacillus reuteri in its biofilm state contribute to its beneficial effects in a rat model of experimental necrotizing enterocolitis.

INTRODUCTION: Necrotizing enterocolitis (NEC) remains a significant surgical emergency in neonates. We have demonstrated the efficacy of Lactobacillus reuteri (Lr) in protecting against experimental NEC when administered as a biofilm by incubation with maltose loaded dextranomer microspheres. Lr possesses antimicrobial and anti-inflammatory properties. We developed mutant strains of Lr to examine the importance of its antimicrobial and anti-inflammatory properties in protecting the intestines from NEC. METHODS: Premature rat pups were exposed to hypoxia/hypothermia/hypertonic feeds to induce NEC. To examine the importance of antimicrobial reuterin and anti-inflammatory histamine, pups received either native or mutant forms of Lr, in either its planktonic or biofilm states, prior to induction of NEC. Intestinal histology was examined upon sacrifice. RESULTS: Compared to no treatment, administration of a single dose of Lr in its biofilm state significantly decreased the incidence of NEC (67% vs. 18%, p < 0.0001), whereas Lr in its planktonic state had no significant effect. Administration of reuterin-deficient or histamine-deficient forms of Lr, in either planktonic or biofilm states, resulted in significant loss of efficacy. CONCLUSION: Antimicrobial and anti-inflammatory effects of Lr contribute to its beneficial effects against NEC. This suggests that both infectious and inflammatory components contribute to the etiology of NEC.

Assessing effective mask use by the public in two countries: an observational study.

OBJECTIVES: During the COVID-19 pandemic wearing a mask in public has been recommended in some settings and mandated in others. How often this advice is followed, how well, and whether it inadvertently leads to more disease transmission opportunities due to a combination of improper use and physical distancing lapses is unknown. DESIGN: Cross-sectional observational study performed in June-August 2020. SETTING: Eleven outdoor and indoor public settings (some with mandated mask use, some without) each in Toronto, Ontario, and in Portland, Oregon. PARTICIPANTS: All passers-by in the study settings. OUTCOME MEASURES: Mask use, incorrect mask use, and number of breaches (ie, coming within 2 m of someone else where both parties were not properly masked). RESULTS: We observed 36 808 persons, the majority of whom were estimated to be aged 31-65 years (49%). Two-thirds (66.7%) were wearing a mask and 13.6% of mask-wearers wore them incorrectly. Mandatory mask-use settings were overwhelmingly associated with mask use (adjusted OR 79.2; 95% CI 47.4 to 135.1). Younger age, male sex, Torontonians, and public transit or airport settings (vs in a store) were associated with lower adjusted odds of wearing a mask. Mandatory mask-use settings were associated with lower adjusted odds of mask error (OR 0.30; 95% CI 0.14 to 0.73), along with female sex and Portland subjects. Subjects aged 81+ years (vs 31-65 years) and those on public transit and at the airport (vs stores) had higher odds of mask errors. Mask-wearers had a large reduction in adjusted mean number of breaches (rate ratio (RR) 0.19; 95% CI 0.17 to 0.20). The 81+ age group had the largest association with breaches (RR 7.77; 95% CI 5.32 to 11.34). CONCLUSIONS: Mandatory mask use was associated with a large increase in mask-wearing. Despite 14% of them wearing their masks incorrectly, mask users had a large reduction in the mean number of breaches (disease transmission opportunities). The elderly and transit users may warrant public health interventions aimed at improving mask use.