Racial and ethnic disparities in motor vehicle crash-related outcomes in North Carolina surrounding the COVID-19 pandemic.

Long-term impacts of the COVID-19 pandemic on racial and ethnic disparities in motor vehicle crash (MVC) injuries and death are poorly understood. This study aimed to characterize trends and investigate the heterogeneity of MVC-related disparities in North Carolina across several data sources. Crash reports, emergency department visit records, and death certificates from 2018 to 2021 were used to calculate monthly population-rates of MVC-related public health outcomes. We estimated trendlines using joinpoint regression and compared outcomes across racial and ethnic classifications. MVC and MVC-related injury rates declined in conjunction with NC's stay-at-home order, while rates of severe outcomes remained unimpacted. By December 2021 rates of MVC-related outcomes met or exceeded pre-pandemic levels, with the highest rates observed among non-Hispanic Black individuals. Racial and ethnic disparities in MVC-related outcomes remained prevalent throughout the COVID-19 pandemic. These results highlight the importance of a holistic approach to traffic injury surveillance when assessing the impact of MVCs.

Time restricted eating as a weight loss intervention in adults with obesity.

OBJECTIVES: Time-restricted eating (TRE) is a weight management approach in which food is consumed only within a specific period each day. The simplicity of this approach is appealing, but its efficacy is not known. The aim of this pilot cohort study was to assess adherence to TRE and its effects on weight and lipid profile. METHODS: Fifty participants with obesity attempted to follow TRE for 12 weeks. Surveys were conducted weekly over the phone to assess treatment adherence and ratings; and at 6 and 12 weeks, participants attended the clinic to be weighed, have their blood pressure taken and provide a blood sample for lipid profile. Treatment results were compared with data from previous comparable cohorts using other weight management methods. RESULTS: Mean age of the participants was 50 (SD = 12.0), mean weight 97kg (SD = 17.1), mean BMI = 35 (SD = 4.0) and most were female (74%). At weeks 6 and 12, 64% and 58% of participants continued to practice TRE on at least five days/week. Using the 'last observation carried forward' imputation, mean (SD) weight loss was 2.0 (1.7) kg and 2.6 (2.6) kg at 6 and 12 weeks. Among participants who provided follow-up data, those who adhered to the intervention for at least five days/week recorded greater weight loss than those with lower adherence (week 6: 2.5 (1.7) vs 1.0 (1.3), p = 0.003; week 12: 3.5 (2.7) vs 1.3 (2.0), p = 0.001). A total of 26% of the sample lost at least 5% of their body weight at 12 weeks. The intervention had no effect on blood pressure or lipid profile. CONCLUSIONS: TRE results were modest, but at least on par with those achieved with more complex interventions, and weight loss did not decline at 12 weeks. A formal trial of the intervention is warranted.

Stakeholder's Perceptions of Mexico's Federal Corn Flour Fortification Program: A Qualitative Study.

BACKGROUND: In Mexico, the fortification of corn and wheat flours with iron, zinc, and folic acid and the restoration of B-vitamins is a mandatory program. However, the monitoring and evaluation (M&E) of this fortification process is not well understood. Thus, the purpose of the study was to understand the M&E of the food fortification program in Mexico, with an emphasis on technology research and development. METHODS: Open-ended exploratory interviews were conducted with food technology representatives (n = 9), food science academic faculty (n = 1), president of a private tortilla-making federation (n = 1), and representatives of the federal monitoring agency (n = 2). Interviews were transcribed and themes were identified using the content analysis methodology. Inter-rater reliability was assessed by calculating an intraclass correlation coefficient (ICC) between the raters (n = 3). RESULTS: A total of 49 codes were identified that resulted in three overarching themes, manufacturing/processing, monitoring logistics, and nutrition. Overall, there is a need for more robust internal and external M&E with Mexico's fortification program to improve the manufacturing/processing of fortifying the tortillas, the monitoring of this fortification program, and the impact the fortified tortillas have on the nutritional status of the Mexican population. The overall ICC was 0.87. CONCLUSIONS: The present study can be used to gain insight into Mexico's fortification program and to inform food fortification policymakers of best practices.

Performance Factors Influencing Efficacy and Effectiveness of Iron Fortification Programs of Condiments for Improving Anemia Prevalence and Iron Status in Populations: A Systematic Review.

Iron fortification of staple foods is a common practice around the world to reduce the prevalence of iron-deficiency anemia. More recently, fortified condiments, including salts, sauces, and powders, have been tested in various efficacy trials. However, there is limited information on how nutritional, environmental, and experimental factors affect their efficacy and effectiveness. The purpose of the present work was to systematically review performance factors affecting the efficacy of condiment fortification trials. Three databases were searched using a standardized keyword search and included based on four-point inclusion criteria. Studies were evaluated against a quality assessment tool and effect sizes were calculated. Studies were ranked as low or high performing, based on whether or not they significantly improved iron-deficiency outcomes (hemoglobin, anemia prevalence, and ferritin levels). Of the 955 retrieved studies, 23 were included-of which, nine performed poorly, eight performed highly, and six were classified as neither because they did not meet the criteria of assessing the three iron outcomes. Results showed that unsuccessful trials did not consider environmental factors such as parasitic infections, nutritional factors such as micronutrient deficiencies other than iron, consumer acceptability of the product or experimental factors such as monitoring and adherence to the trials. Two common performing factors identified among those studies performing highly vs. those that did not were the control of sensory changes and monitoring of consumption compliance (i.e., dose delivery). The present work can be used as decision-making support for nutrition policy makers when determining the appropriate implementation of condiment fortification programs.

Development of a Paper-Based Sensor Compatible with a Mobile Phone for the Detection of Common Iron Formulas Used in Fortified Foods within Resource-Limited Settings.

A lack of quality control tools limits the enforcement of fortification policies. In alignment with the World Health Organization's ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable), a paper-based assay that interfaces with a smartphone application for the quantification of iron fortificants is presented. The assay is based on the Ferrozine colorimetric method. The reaction started after deposition of the 5 µL aqueous sample and drying. After developing color, pixel intensity values were obtained using a smartphone camera and image processing software or a mobile application, Nu3px. From these values, the actual iron concentration from ferrous sulfate and ferrous fumarate was calculated. The limits of detection, quantification, linearity, range, and errors (systematic and random) were ascertained. The paper-based values from real samples (wheat flour, nixtamalized corn flour, and infant formula) were compared against atomic emission spectroscopy. The comparison of several concentrations of atomic iron between the spectrophotometric and paper-based assays showed a strong positive linear correlation (y = 47.01x + 126.18; R2 = 0.9932). The dynamic range (5.0-100 µg/mL) and limit of detection (3.691 µg/mL) of the paper-based assay are relevant for fortified food matrices. Random and systematic errors were 15.9% and + 8.65 µg/g food, respectively. The concept can be applied to limited-resource settings to measure iron in fortified foods.

Evaluation of Micronutrient Sensors for Food Matrices in Resource-Limited Settings: A Systematic Narrative Review.

In resource-limited settings, mass food fortification is a common strategy to ensure the population consumes appropriate quantities of essential micronutrients. Food and government organizations in these settings, however, lack tools to monitor the quality and compliance of fortified products and their efficacy to enhance nutrient status. The World Health Organization has developed general guidelines known as ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable to end-users) to aid the development of useful diagnostic tools for these settings. These guidelines assume performance aspects such as sufficient accuracy, reliability, and validity. The purpose of this systematic narrative review is to examine the micronutrient sensor literature on its adherence towards the ASSURED criteria along with accuracy, reliability, and validation when developing micronutrient sensors for resource-limited settings. Keyword searches were conducted in three databases: Web of Science, PubMed, and Scopus and were based on 6-point inclusion criteria. A 16-question quality assessment tool was developed to determine the adherence towards quality and performance criteria. Of the 2,365 retrieved studies, 42 sensors were included based on inclusion/exclusion criteria. Results showed that improvements to the current sensor design are necessary, especially their affordability, user-friendliness, robustness, equipment-free, and deliverability within the ASSURED criteria, and accuracy and validity of the additional criteria to be useful in resource-limited settings. Although it requires further validation, the 16-question quality assessment tool can be used as a guide in the development of sensors for resource-limited settings.

High-Throughput Flow Cytometry Screening of Multidrug Efflux Systems.

The resistance nodulation cell division (RND) family of proteins are inner membrane transporters that associate with periplasmic adaptor proteins and outer membrane porins to affect substrate transport from the cytosol and periplasm in Gram-negative bacteria. Various structurally diverse compounds are substrates of RND transporters. Along with their notable role in antibiotic resistance, these transporters are essential for niche colonization, quorum sensing, and virulence as well as for the removal of fatty acids and bile salts. As such, RNDs are an attractive target for antimicrobial development. However, while enhancing the utility of antibiotics with an RND inhibitor is an appealing concept, only a small core of chemotypes has been identified as efflux pump inhibitors (EPIs). Thus, our key objective is the development and validation of an efflux profiling and discovery strategy for RND model systems. Here we describe a flow cytometric dye accumulation assay that uses fluorescein diacetate (FDA) to interrogate the model Gram-negative pathogens Escherichia coli, Franscisella tularensis, and Burkholderia pseudomallei. Fluorochrome retention is increased in the presence of known efflux inhibitors and in RND deletion strains. The assay can be used in a high-throughput format to evaluate efflux of dye-substrate candidates and to screen chemical libraries for novel EPIs. Triaged compounds that inhibit efflux in pathogenic strains are tested for growth inhibition and antibiotic potentiation using microdilution culture plates in a select agent Biosafety Level-3 (BSL3) environment. This combined approach demonstrates the utility of flow cytometric analysis for efflux activity and provides a useful platform in which to characterize efflux in pathogenic Gram-negative bacteria. Screening small molecule libraries for novel EPI candidates offers the potential for the discovery of new classes of antibacterial compounds.

Pollen concentration and asthma exacerbations in Wake County, North Carolina, 2006-2012.

Pollen has been generally linked to an increased risk for asthma exacerbation. However, the delayed effect (lag), the length of effect duration, and the association heterogeneity by pollen types have not been well characterized. Short-term associations between ambient concentration of various pollen types (tree, grass, and weed) and emergency department (ED) visits for asthma were assessed using data in Wake County, North Carolina, during 2006-2012. Distributed lag nonlinear models (DLNM) were used to characterize the associations, while adjusting for air pollutants, meteorological, and temporal factors. A strong association between same-day tree pollen and asthma ED visits was detected. This association lasted four days, with a 4-day cumulative risk ratio (RR) up to 2.10 (3500 grains/m(3) vs. 0 grains/m(3), 95% confidence interval [CI]=1.21-3.65). The associations of asthma ED visits with weed pollen and grass pollen were weak, suggestively starting from lag 2 and lasting 3 days, with the strongest association a 3-day cumulative RR of 1.08 (32 grains/m(3) vs. 0 grains/m(3), 95% CI=1.01-1.15) and 1.05 (11 grains/m(3) vs. 0 grains/m(3), 95% CI=1.00-1.11). Our results indicate that the association of ambient pollen and asthma exacerbation vary by pollen type, both quantitatively and temporally. These findings have important implications for optimizing targeted allergic disease prevention and management, and helping understand the etiology of ambient exposure-induced allergic diseases.

Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential.

Autophagy is a conserved homeostatic process active in all human cells and affecting a spectrum of diseases. Here we use a pharmaceutical screen to discover new mechanisms for activation of autophagy. We identify a subset of pharmaceuticals inducing autophagic flux with effects in diverse cellular systems modelling specific stages of several human diseases such as HIV transmission and hyperphosphorylated tau accumulation in Alzheimer's disease. One drug, flubendazole, is a potent inducer of autophagy initiation and flux by affecting acetylated and dynamic microtubules in a reciprocal way. Disruption of dynamic microtubules by flubendazole results in mTOR deactivation and dissociation from lysosomes leading to TFEB (transcription factor EB) nuclear translocation and activation of autophagy. By inducing microtubule acetylation, flubendazole activates JNK1 leading to Bcl-2 phosphorylation, causing release of Beclin1 from Bcl-2-Beclin1 complexes for autophagy induction, thus uncovering a new approach to inducing autophagic flux that may be applicable in disease treatment.

Identification of inhibitors of vacuolar proton-translocating ATPase pumps in yeast by high-throughput screening flow cytometry.

Fluorescence intensity of the pH-sensitive carboxyfluorescein derivative 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) was monitored by high-throughput flow cytometry in living yeast cells. We measured fluorescence intensity of BCECF trapped in yeast vacuoles, acidic compartments equivalent to lysosomes where vacuolar proton-translocating ATPases (V-ATPases) are abundant. Because V-ATPases maintain a low pH in the vacuolar lumen, V-ATPase inhibition by concanamycin A alkalinized the vacuole and increased BCECF fluorescence. Likewise, V-ATPase-deficient mutant cells had greater fluorescence intensity than wild-type cells. Thus, we detected an increase of fluorescence intensity after short- and long-term inhibition of V-ATPase function. We used yeast cells loaded with BCECF to screen a small chemical library of structurally diverse compounds to identify V-ATPase inhibitors. One compound, disulfiram, enhanced BCECF fluorescence intensity (although to a degree beyond that anticipated for pH changes alone in the mutant cells). Once confirmed by dose-response assays (EC(50)=26 microM), we verified V-ATPase inhibition by disulfiram in secondary assays that measured ATP hydrolysis in vacuolar membranes. The inhibitory action of disulfiram against V-ATPase pumps revealed a novel effect previously unknown for this compound. Because V-ATPases are highly conserved, new inhibitors identified could be used as research and therapeutic tools in cancer, viral infections, and other diseases where V-ATPases are involved.