Cumulative effect of loneliness and social isolation on health outcomes among older adults.

OBJECTIVES: Loneliness and social isolation are described similarly yet are distinct constructs. Numerous studies have examined each construct separately; however, less effort has been dedicated to exploring the impacts in combination. This study sought to describe the cumulative effects on late-life health outcomes. METHOD: Survey data collected in 2018-2019 of a randomly sampled population of US older adults, age 65+, were utilized (N = 6,994). Survey measures included loneliness and social isolation using the UCLA-3 Loneliness Scale and Social Network Index. Participants were grouped into four categories based on overlap. Groups were lonely only, socially isolated only, both lonely and socially isolated, or neither. Bivariate and adjusted associations were examined. RESULTS: Among participants (mean age = 76.5 years), 9.8% (n = 684) were considered lonely only, 20.6% (n = 1,439) socially isolated only, 9.1% (n = 639) both lonely and socially isolated, and 60.5% (n = 4,232) neither. Those considered both lonely and socially isolated were more likely to be older, female, less healthy, depressed, with lower quality of life and greater medical costs in bivariate analyses. In adjusted results, participants who were both lonely and socially isolated had significantly higher rates of ER visits and marginally higher medical costs. CONCLUSION: Results demonstrate cumulative effects of these constructs among older adults. Findings not only fill a gap in research exploring the impacts of loneliness and social isolation later in life, but also confirm the need for approaches targeting older adults who are both lonely and socially isolated. As the COVID-19 pandemic continues, this priority will continue to be urgent for older adults.

Use of a Probiotic to Enhance Iron Absorption in a Randomized Trial of Pediatric Patients Presenting with Iron Deficiency.

OBJECTIVE: To evaluate the efficacy of low dose ferrous sulfate for the treatment of iron deficiency and if the probiotic Lactobacillus plantarum 299v (LP299v) enhances treatment. STUDY DESIGN: This randomized, double-blinded, controlled trial of the treatment of iron deficiency in children compared the use of low-dose ferrous sulfate (1-3 mg/kg/day), with or without probiotic (LP299v). RESULTS: Serum ferritin level increased in all children from a baseline of 23.7 ng/mL to 45.4 ng/mL after 6-8 weeks of treatment. There was no significant difference in the increase in serum ferritin in children taking the probiotic LP299v compared with controls (23.2 vs 20.0 ng/mL, respectively). Additionally, an increase in ferritin level was not significantly associated with probiotic use when controlling for other factors, including child weight and dosing. Overall, the treatments were well-tolerated, with mild side effects. CONCLUSIONS: Treatment with low-dose ferrous sulfate is well-tolerated and effective in correcting iron deficiency in children. However, the probiotic LP299v did not enhance treatment. Further attention should examine the dose-response effect in children, including an alternate day dosing schedule. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01617044.

Rate of Airway Intervention for Croup at a Tertiary Children's Hospital 2015-2016.

BACKGROUND: Croup admission decision making is challenging because the rate of further interventions after stabilization is unclear. OBJECTIVE: We sought to describe rates of inpatient racemic epinephrine (IRE) and additional inpatient airway interventions (IAI) (oxygen or heliox therapy, intubation, or transfer to an intensive care unit) among patients presenting to a tertiary children's hospital with croup. METHODS: This was a retrospective descriptive study including patients (3 months to 8 years of age) with an emergency department (ED)/inpatient encounter for croup from January 1, 2015 to December 31, 2016 at a tertiary children's hospital. We excluded intensive care unit direct admissions and patients with bronchiolitis/asthma/pneumonia. We compared 3 groups (a weighted random 5% sample of patients evaluated in ED only, and those admitted with or without IRE/IAI) using Kruskal-Wallis, Pearson χ2, or the Fischer exact test, where appropriate. We used multivariate analysis to compare demographics and preadmission racemic epinephrine (RE) with rates of IRE/IAI in admitted patients. RESULTS: We included 588 patients (194 discharged from the ED, 394 admitted). In admitted patients, 20.8% (82/394) had IRE/IAI, most commonly IRE (20.0%, 79/394). Three admitted patients (0.76%) had IAI. Overall, patients with 2 outside hospital/ED doses of RE had a 12.1% rate of IRE/IAI (23.5% if ≥3 RE doses). Patients with ≥3 preadmission RE doses were more likely to have IRE/IAI compared with 2 RE (adjusted odds ratio = 2.08 [95% confidence interval 1.15-3.76]; p = 0.02); there were no other significant associations. CONCLUSIONS: We found a low rate of IRE/IAI after ED management in patients with croup and no significant associations aside from preadmission RE doses. These findings may be considered in admission decisions.

Hippotherapy in Rehabilitation Care for Children With Neurological Impairments and Developmental Delays: A Case Series.

PURPOSE: This report assesses functional mobility in children with neurological impairments and documented gross motor delays, before and after receiving either hippotherapy or standard outpatient physical therapy (PT). SUMMARY OF KEY POINTS: This is a case-series report using data previously collected for a discontinued randomized controlled trial, in which participants received hippotherapy or standard outpatient clinic PT for a 12-week treatment period. Results demonstrated both subjective and objective functional mobility improvements after treatment in participants receiving hippotherapy and standard outpatient PT, as determined by the Peabody Developmental Motor Scales-2, the Pediatric Evaluation of Disability Inventory, and the Goal Attainment Scaling. STATEMENT OF CONCLUSION AND RECOMMENDATIONS FOR CLINICAL PRACTICE:: When compared with standard outpatient PT, hippotherapy appears to be a viable treatment strategy for children aged 2 to 5 years with neurological impairments and gross motor delays, but additional research in this area is needed to validate findings.

What does a person's eating identity add to environmental influences on fruit and vegetable intake?

OBJECTIVE: To evaluate whether knowledge of a person's eating identity (EI) can explain any additional variation in fruit and vegetable intake above and beyond that explained by food environment characteristics, perceptions of the food environment, and shopping behaviors. DESIGN: Cross-sectional study. SETTING: A total of 968 adults were recruited for a telephone survey by the Survey Research Laboratory in an eight-county region in South Carolina. SUBJECTS: The survey queried information on shopping behaviors, perceptions of the food environment, demographic and address information, fruit and vegetable intake, and EI. EI was assessed using the Eating Identity Type Inventory, a 12-item instrument that differentiates four eating identity types: healthy, emotional, meat, and picky. Statistical analyses were restricted to 819 participants with complete data. RESULTS: Healthy EI and picky EI were significantly and directly related to fruit and vegetable intake, with coefficients of 0.31 (p-value<0.001) for healthy EI and -0.16 (p-value<0.001) for picky EI, whereas emotional EI (ß = 0.00, p-value = 0.905) and meat EI (ß = -0.04, p-value = 0.258) showed no association. Shopping frequency also directly and significantly influenced fruit and vegetable intake (ß = 0.13, p-value = 0.033). With the inclusion of EI, 16.3% of the variation in fruit and vegetable intake was explained. CONCLUSIONS: Perceptions and GIS-based measures of environmental factors alone do not explain a substantial amount of variation in fruit and vegetable intake. EI, especially healthy EI and picky EI, is an important, independent predictor of fruit and vegetable intake and contributes significantly to explaining the variation in fruit and vegetable intake.

Association between store food environment and customer purchases in small grocery stores, gas-marts, pharmacies and dollar stores.

BACKGROUND: Purchases at small/non-traditional food stores tend to have poor nutritional quality, and have been associated with poor health outcomes, including increased obesity risk The purpose of this study was to examine whether customers who shop at small/non-traditional food stores with more health promoting features make healthier purchases. METHODS: In a cross-sectional design, data collectors assessed store features in a sample of 99 small and non-traditional food stores not participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in Minneapolis/St. Paul, MN in 2014. Customer intercept interviews (n = 594) collected purchase data from a bag check and demographics from a survey. Store measures included fruit/vegetable and whole grain availability, an overall Healthy Food Supply Score (HFSS), healthy food advertisements and in-store placement, and shelf space of key items. Customer nutritional measures were analyzed using Nutrient Databases System for Research (NDSR), and included the purchase of ≥1 serving of fruits/vegetables; ≥1 serving of whole grains; and overall Healthy Eating Index-2010 (HEI-2010) score for foods/beverages purchased. Associations between store and customer measures were estimated in multilevel linear and logistic regression models, controlling for customer characteristics and store type. RESULTS: Few customers purchased fruits and vegetables (8%) or whole grains (8%). In fully adjusted models, purchase HEI-2010 scores were associated with fruit/vegetable shelf space (p = 0.002) and the ratio of shelf space devoted to healthy vs. less healthy items (p = 0.0002). Offering ≥14 varieties of fruit/vegetables was associated with produce purchases (OR 3.9, 95% CI 1.2-12.3), as was having produce visible from the store entrance (OR 2.3 95% CI 1.0 to 5.8), but whole grain availability measures were not associated with whole grain purchases. CONCLUSIONS: Strategies addressing both customer demand and the availability of healthy food may be necessary to improve customer purchases. TRIAL REGISTRATION: ClinialTrials.gov: NCT02774330 . Registered May 4, 2016 (retrospectively registered).

Decision trees in epidemiological research.

BACKGROUND: In many studies, it is of interest to identify population subgroups that are relatively homogeneous with respect to an outcome. The nature of these subgroups can provide insight into effect mechanisms and suggest targets for tailored interventions. However, identifying relevant subgroups can be challenging with standard statistical methods. MAIN TEXT: We review the literature on decision trees, a family of techniques for partitioning the population, on the basis of covariates, into distinct subgroups who share similar values of an outcome variable. We compare two decision tree methods, the popular Classification and Regression tree (CART) technique and the newer Conditional Inference tree (CTree) technique, assessing their performance in a simulation study and using data from the Box Lunch Study, a randomized controlled trial of a portion size intervention. Both CART and CTree identify homogeneous population subgroups and offer improved prediction accuracy relative to regression-based approaches when subgroups are truly present in the data. An important distinction between CART and CTree is that the latter uses a formal statistical hypothesis testing framework in building decision trees, which simplifies the process of identifying and interpreting the final tree model. We also introduce a novel way to visualize the subgroups defined by decision trees. Our novel graphical visualization provides a more scientifically meaningful characterization of the subgroups identified by decision trees. CONCLUSIONS: Decision trees are a useful tool for identifying homogeneous subgroups defined by combinations of individual characteristics. While all decision tree techniques generate subgroups, we advocate the use of the newer CTree technique due to its simplicity and ease of interpretation.

Food and beverage purchases in corner stores, gas-marts, pharmacies and dollar stores.

OBJECTIVE: Little is known about customer purchases of foods and beverages from small and non-traditional food retailers (i.e. corner stores, gas-marts, dollar stores and pharmacies). The present study aimed to: (i) describe customer characteristics, shopping frequency and reasons for shopping at small and non-traditional food retailers; and (ii) describe food/beverage purchases and their nutritional quality, including differences across store type. DESIGN: Data were collected through customer intercept interviews. Nutritional quality of food/beverage purchases was analysed; a Healthy Eating Index-2010 (HEI-2010) score for purchases was created by aggregating participant purchases at each store. SETTING: Small and non-traditional food stores that were not WIC-authorized in Minneapolis and St. Paul, MN, USA. SUBJECTS: Customers (n 661) from 105 food retailers. RESULTS: Among participants, 29 % shopped at the store at least once daily; an additional 44 % shopped there at least once weekly. Most participants (74 %) cited convenient location as the primary draw to the store. Customers purchased a median of 2262 kJ (540 kcal), which varied by store type (P=0·04). The amount of added sugar far surpassed national dietary recommendations. At dollar stores, participants purchased a median of 5302 kJ (1266 kcal) for a median value of $US 2·89. Sugar-sweetened beverages were the most common purchase. The mean HEI-2010 score across all stores was 36·4. CONCLUSIONS: Small and non-traditional food stores contribute to the urban food environment. Given the poor nutritional quality of purchases, findings support the need for interventions that address customer decision making in these stores.

Fast-food consumption, diet quality and body weight: cross-sectional and prospective associations in a community sample of working adults.

OBJECTIVE: To examine the association between fast-food consumption, diet quality and body weight in a community sample of working adults. DESIGN: Cross-sectional and prospective analysis of anthropometric, survey and dietary data from adults recruited to participate in a worksite nutrition intervention. Participants self-reported frequency of fast-food consumption per week. Nutrient intakes and diet quality, using the Healthy Eating Index-2010 (HEI-2010), were computed from dietary recalls collected at baseline and 6 months. SETTING: Metropolitan medical complex, Minneapolis, MN, USA. SUBJECTS: Two hundred adults, aged 18-60 years. RESULTS: Cross-sectionally, fast-food consumption was significantly associated with higher daily total energy intake (ß=72·5, P=0·005), empty calories (ß=0·40, P=0·006) and BMI (ß=0·73, P=0·011), and lower HEI-2010 score (ß=-1·23, P=0·012), total vegetables (ß=-0·14, P=0·004), whole grains (ß=-0·39, P=0·005), fibre (ß=-0·83, P=0·002), Mg (ß=-6·99, P=0·019) and K (ß=-57·5, P=0·016). Over 6 months, change in fast-food consumption was not significantly associated with changes in energy intake or BMI, but was significantly inversely associated with total intake of vegetables (ß=-0·14, P=0·034). CONCLUSIONS: Frequency of fast-food consumption was significantly associated with higher energy intake and poorer diet quality cross-sectionally. Six-month change in fast-food intake was small, and not significantly associated with overall diet quality or BMI.

Geographic measures of retail food outlets and perceived availability of healthy foods in neighbourhoods.

OBJECTIVE: To examine associations between geographic measures of retail food outlets and perceived availability of healthy foods. DESIGN: Cross-sectional. SETTING: A predominantly rural, eight-county region of South Carolina, USA. SUBJECTS: Data from 705 household shoppers were analysed using ordinary least-squares regression to examine relationships between geographic measures (presence and distance) of food outlets obtained via a geographic information system and perceived availability of healthy foods (fresh fruits and vegetables and low-fat foods). RESULTS: The presence of a supermarket within an 8·05 km (5-mile) buffer area was significantly associated with perceived availability of healthy foods (ß=1·09, P=0·025) when controlling for all other food outlet types. However, no other derived geographic presence measures were significant predictors of perceived availability of healthy foods. Distances to the nearest supermarket (ß=-0·16, P=0·003), dollar and variety store (ß=-0·15, P=0·005) and fast-food restaurant (ß=0·11, P=0·015) were all significantly associated with perceptions of healthy food availability. CONCLUSIONS: Our results suggest that distance to food outlets is a significant predictor of healthy food perceptions, although presence is sensitive to boundary size. Our study contributes to the understanding and improvement of techniques that characterize individuals' food options in their community.

Healthfulness of Foods Advertised in Small and Nontraditional Urban Stores in Minneapolis-St. Paul, Minnesota, 2014.

INTRODUCTION: Shopping at small food stores, such as corner stores and convenience stores, is linked with unhealthful food and beverage purchases, poor diets, and high risk of obesity. However, information on how foods and beverages are marketed at small stores is limited. The objective of this study was to examine advertisements and product placements for healthful and less healthful foods and beverages at small stores in Minneapolis-St. Paul, Minnesota. METHODS: We conducted in-store audits of 119 small and nontraditional food retailers (corner/small grocery stores, food-gas marts, pharmacies, and dollar stores) randomly selected from licensing lists in Minneapolis-St. Paul in 2014. We analyzed data on exterior and interior advertisements of foods and beverages and product placement. RESULTS: Exterior and interior advertisements for healthful foods and beverages were found in less than half of stores (exterior, 37% [44 of 119]; interior, 20% [24 of 119]). Exterior and interior advertisements for less healthful items were found in approximately half of stores (exterior, 46% [55 of 119]); interior, 66% [78 of 119]). Of the 4 store types, food-gas marts were most likely to have exterior and interior advertisements for both healthful and less healthful items. Corner/small grocery stores and dollar stores had fewer advertisements of any type. Most stores (77%) had at least 1 healthful item featured as an impulse buy (ie, an item easily reached at checkout), whereas 98% featured at least 1 less healthful item as an impulse buy. CONCLUSION: Findings suggest imbalanced advertising and product placement of healthful and less healthful foods and beverages at small food stores in Minneapolis-St. Paul; less healthful items were more apt to be featured as impulse buys. Future interventions and polices should encourage reductions in advertisements and impulse-buy placements of unhealthful products, particularly in food-gas marts, and encourage advertisements of healthful products.

Scale effects in food environment research: Implications from assessing socioeconomic dimensions of supermarket accessibility in an eight-county region of South Carolina.

Choice of neighborhood scale affects associations between environmental attributes and health-related outcomes. This phenomenon, a part of the modifiable areal unit problem, has been described fully in geography but not as it relates to food environment research. Using two administrative-based geographic boundaries (census tracts and block groups), supermarket geographic measures (density, cumulative opportunity and distance to nearest) were created to examine differences by scale and associations between three common U.S. Census-based socioeconomic status (SES) characteristics (median household income, percentage of population living below poverty and percentage of population with at least a high school education) and a summary neighborhood SES z-score in an eight-county region of South Carolina. General linear mixed-models were used. Overall, both supermarket density and cumulative opportunity were higher when using census tract boundaries compared to block groups. In analytic models, higher median household income was significantly associated with lower neighborhood supermarket density and lower cumulative opportunity using either the census tract or block group boundaries, and neighborhood poverty was positively associated with supermarket density and cumulative opportunity. Both median household income and percent high school education were positively associated with distance to nearest supermarket using either boundary definition, whereas neighborhood poverty had an inverse association. Findings from this study support the premise that supermarket measures can differ by choice of geographic scale and can influence associations between measures. Researchers should consider the most appropriate geographic scale carefully when conducting food environment studies.

Neighborhood fast food availability and fast food consumption.

Recent nutritional and public health research has focused on how the availability of various types of food in a person's immediate area or neighborhood influences his or her food choices and eating habits. It has been theorized that people living in areas with a wealth of unhealthy fast-food options may show higher levels of fast-food consumption, a factor that often coincides with being overweight or obese. However, measuring food availability in a particular area is difficult to achieve consistently: there may be differences in the strict physical locations of food options as compared to how individuals perceive their personal food availability, and various studies may use either one or both of these measures. The aim of this study was to evaluate the association between weekly fast-food consumption and both a person's perceived availability of fast-food and an objective measure of fast-food presence - Geographic Information Systems (GIS) - within that person's neighborhood. A randomly selected population-based sample of eight counties in South Carolina was used to conduct a cross-sectional telephone survey assessing self-report fast-food consumption and perceived availability of fast food. GIS was used to determine the actual number of fast-food outlets within each participant's neighborhood. Using multinomial logistic regression analyses, we found that neither perceived availability nor GIS-based presence of fast-food was significantly associated with weekly fast-food consumption. Our findings indicate that availability might not be the dominant factor influencing fast-food consumption. We recommend using subjective availability measures and considering individual characteristics that could influence both perceived availability of fast food and its impact on fast-food consumption. If replicated, our findings suggest that interventions aimed at reducing fast-food consumption by limiting neighborhood fast-food availability might not be completely effective.

Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia.

OBJECTIVE: Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia. The aim of this study was to identify the molecular pathogenesis of autosomal recessive hypercholesterolemia in this family. APPROACH AND RESULTS: We used exome sequencing to assess all protein-coding regions of the genome in 3 family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in LIPA that segregated with the diagnosis of hypercholesterolemia. Because homozygosity for mutations in LIPA is known to cause cholesterol ester storage disease, we performed directed follow-up phenotyping by noninvasively measuring hepatic cholesterol content. We observed abnormal hepatic accumulation of cholesterol in the homozygote individuals, supporting the diagnosis of cholesterol ester storage disease. Given previous suggestions of cardiovascular disease risk in heterozygous LIPA mutation carriers, we genotyped E8SJM in >27 000 individuals and found no association with plasma lipid levels or risk of myocardial infarction, confirming a true recessive mode of inheritance. CONCLUSIONS: By integrating observations from Mendelian and population genetics along with directed clinical phenotyping, we diagnosed clinically unapparent cholesterol ester storage disease in the affected individuals from this kindred and addressed an outstanding question about risk of cardiovascular disease in LIPA E8SJM heterozygous carriers.

Environmental influences on fruit and vegetable intake: results from a path analytic model.

OBJECTIVE: Fruit and vegetable (F&V) intake is influenced by behavioural and environmental factors, but these have rarely been assessed simultaneously. We aimed to quantify the relative influence of supermarket availability, perceptions of the food environment and shopping behaviour on F&V intake. DESIGN: A cross-sectional study. SETTING: Eight counties in South Carolina, USA, with verified locations of all supermarkets. SUBJECTS: A telephone survey of 831 household food shoppers ascertained F&V intake with a seventeen-item screener, primary food store location, shopping frequency and perceptions of healthy food availability, and supermarket availability was calculated with a geographic information system. Path analysis was conducted. We report standardized beta coefficients on paths significant at the 0·05 level. RESULTS: Frequency of grocery shopping at primary food store (ß = 0·11) was the only factor exerting an independent, statistically significant direct effect on F&V intake. Supermarket availability was significantly associated with distance to utilized food store (ß = -0·24) and shopping frequency (ß = 0·10). Increased supermarket availability was significantly and positively related to perceived healthy food availability in the neighbourhood (ß = 0·18) and ease of shopping access (ß = 0·09). Collectively considering all model paths linked to perceived availability of healthy foods, this measure was the only other factor to have a significant total effect on F&V intake. CONCLUSIONS: While the majority of the literature to date has suggested an independent and important role of supermarket availability for F&V intake, our study found only indirect effects of supermarket availability and suggests that food shopping frequency and perceptions of healthy food availability are two integral components of a network of influences on F&V intake.

Lipid Nanocarriers-Enabled Delivery of Antibiotics and Antimicrobial Adjuvants to Overcome Bacterial Biofilms.

The opportunistic bacteria growing in biofilms play a decisive role in the pathogenesis of chronic infectious diseases. Biofilm-dwelling bacteria behave differently than planktonic bacteria and are likely to increase resistance and tolerance to antimicrobial therapeutics. Antimicrobial adjuvants have emerged as a promising strategy to combat antimicrobial resistance (AMR) and restore the efficacy of existing antibiotics. A combination of antibiotics and potential antimicrobial adjuvants, (e.g., extracellular polymeric substance (EPS)-degrading enzymes and quorum sensing inhibitors (QSI) can improve the effects of antibiotics and potentially reduce bacterial resistance). In addition, encapsulation of antimicrobials within nanoparticulate systems can improve their stability and their delivery into biofilms. Lipid nanocarriers (LNCs) have been established as having the potential to improve the efficacy of existing antibiotics in combination with antimicrobial adjuvants. Among them, liquid crystal nanoparticles (LCNPs), liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) are promising due to their superior properties compared to traditional formulations, including their greater biocompatibility, higher drug loading capacity, drug protection from chemical or enzymatic degradation, controlled drug release, targeted delivery, ease of preparation, and scale-up feasibility. This article reviews the recent advances in developing various LNCs to co-deliver some well-studied antimicrobial adjuvants combined with antibiotics from different classes. The efficacy of various combination treatments is compared against bacterial biofilms, and synergistic therapeutics that deserve further investigation are also highlighted. This review identifies promising LNCs for the delivery of combination therapies that are in recent development. It discusses how LNC-enabled co-delivery of antibiotics and adjuvants can advance current clinical antimicrobial treatments, leading to innovative products, enabling the reuse of antibiotics, and providing opportunities for saving millions of lives from bacterial infections.

Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome.

BACKGROUND: A sexual dimorphism exists in the incidence and prevalence of coronary artery disease--men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. METHODS: We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. FINDINGS: Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. INTERPRETATION: The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. FUNDING: British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.

Variation in low food access areas due to data source inaccuracies.

Several spatial measures of community food access identifying so called "food deserts" have been developed based on geospatial information and commercially-available, secondary data listings of food retail outlets. It is not known how data inaccuracies influence the designation of Census tracts as areas of low access. This study replicated the U.S. Department of Agriculture Economic Research Service (USDA ERS) food desert measure and the Centers for Disease Control and Prevention (CDC) non-healthier food retail tract measure in two secondary data sources (InfoUSA and Dun & Bradstreet) and reference data from an eight-county field census covering169 Census tracts in South Carolina. For the USDA ERS food deserts measure accuracy statistics for secondary data sources were 94% concordance, 50-65% sensitivity, and 60-64% positive predictive value (PPV). Based on the CDC non-healthier food retail tracts both secondary data demonstrated 88-91% concordance, 80-86% sensitivity and 78-82% PPV. While inaccuracies in secondary data sources used to identify low food access areas may be acceptable for large-scale surveillance, verification with field work is advisable for local community efforts aimed at identifying and improving food access.

Lyophilized Lipid Liquid Crystalline Nanoparticles as an Antimicrobial Delivery System.

Lipid liquid crystalline nanoparticles (LCNPs) are unique nanocarriers that efficiently deliver antimicrobials through biological barriers. Yet, their wide application as an antimicrobial delivery system is hindered by their poor stability in aqueous dispersions. The production of dried LCNP powder via lyophilization is a promising approach to promote the stability of LCNPs. However, the impact of the process on the functionality of the loaded hydrophobic cargoes has not been reported yet. Herein, we investigated the potential of lyophilization to produce dispersible dry LCNPs loaded with a hydrophobic antimicrobial compound, gallium protoporphyrin (GaPP). The effect of lyophilization on the physicochemical characteristics and the antimicrobial activity of rehydrated GaPP-LCNPs was studied. The rehydrated GaPP-LCNPs retained the liquid crystalline structure and were monodisperse (PDI: 0.27 ± 0.02), with no significant change in nanoparticle concentration despite the minor increase in hydrodynamic diameter (193 ± 6.5 compared to 173 ± 4.2 prior to freeze-drying). Most importantly, the efficacy of the loaded GaPP as an antimicrobial agent and a photosensitizer was not affected as similar MIC values were obtained against S. aureus (0.125 µg/mL), with a singlet oxygen quantum yield of 0.72. These findings indicate the suitability of lyophilization to produce a dry form of LCNPs and pave the way for future studies to promote the application of LCNPs as an antimicrobial delivery system.

Mimicking the Gastrointestinal Mucus Barrier: Laboratory-Based Approaches to Facilitate an Enhanced Understanding of Mucus Permeation.

The gastrointestinal mucus layer plays a significant role in maintaining gut homeostasis and health, offering protective capacities against the absorption of harmful pathogens as well as commensal gut bacteria and buffering stomach acid to protect the underlying epithelium. Despite this, the mucus barrier is often overlooked during preclinical pharmaceutical development and may pose a significant absorption barrier to high molecular weight or lipophilic drug species. The complex chemical and physical nature of the dynamic mucus layer has proven problematic to reliably replicate in a laboratory setting, leading to the development of multiple mucus models with varying complexity and predictive capacity. This, coupled with the wide range of analysis methods available, has led to a plethora of possible approaches to quantifying mucus permeation; however, the field remains significantly under-represented in biomedical research. For this reason, the development of a concise collation of the available approaches to mucus permeation is essential. In this review, we explore widely utilized mucus mimics ranging in complexity from simple mucin solutions to native mucus preparations for their predictive capacity in mucus permeation analysis. Furthermore, we highlight the diverse range of laboratory-based models available for the analysis of mucus interaction and permeability with a specific focus on in vitro, ex vivo, and in situ models. Finally, we highlight the predictive capacity of these models in correlation with in vivo pharmacokinetic data. This review provides a comprehensive and critical overview of the available technologies to analyze mucus permeation, facilitating the efficient selection of appropriate tools for further advancement in oral drug delivery.