Integrating nutrition and genetic counseling: A case study approach to interprofessional learning.

Interprofessional collaboration is an increasingly important skillset for practicing healthcare professionals including genetic counselors and registered dietitian nutritionists. A multi-part interactive case study activity was created to develop interprofessional skills for graduate students within genetic counseling and medical nutrition training programs at an academic medical center. Feedback from learners who participated in this activity highlights its effect on their post-graduation clinical practice. Additionally, since the implementation of this activity, collaboration between students and faculty members of each program has occurred in other scholarly pursuits, fostering longstanding interprofessional relationships. Similar approaches to interprofessional education could be considered with other healthcare professions or at other institutions as another tool to strengthen practice upon graduation.

Omega-6 and Omega-3 Fatty Acid-Derived Oxylipins from the Lipoxygenase Pathway in Maternal and Umbilical Cord Plasma at Delivery and Their Relationship with Infant Growth.

Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography-tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman's correlations highlighted significant correlations between metabolite levels and infant growth. They were then adjusted for maternal obesity (normal body mass index (BMI: ≤30 kg/m2) vs. obese BMI (>30 kg/m2) and smoking status (never vs. current/former smoker) using linear regression modeling. A p-value < 0.05 was considered statistically significant. Our study demonstrated a diverse panel of oxylipins from the lipoxygenase pathway present at the time of delivery. In addition, both omega-3 and omega-6 oxylipins demonstrated potential influences on the birth length and weight percentiles. The oxylipins present during pregnancy may influence fetal growth and development, suggesting potential metabolites to be used as biomarkers for infant outcomes.

Concentrations of fat-soluble nutrients and blood inflammatory compounds in mother-infant dyads at birth.

BACKGROUND: Perinatal inflammation adversely affects health. Therefore, aims of this IRB-approved study are: (1) compare inflammatory compounds within and between maternal and umbilical cord blood samples at the time of delivery, (2) assess relationships between inflammatory compounds in maternal and cord blood with birth characteristics/outcomes, and (3) assess relationships between blood and placental fat-soluble nutrients with blood levels of individual inflammatory compounds. METHODS: Mother-infant dyads were enrolled (n = 152) for collection of birth data and biological samples of maternal blood, umbilical cord blood, and placental tissue. Nutrient levels included: lutein + zeaxanthin; lycopene; α-, ß-carotene; ß-cryptoxanthin; retinol; α-, γ-, δ-tocopherol. Inflammatory compounds included: tumor necrosis factor-α, superoxide dismutase, interleukins (IL) 1ß, 2, 6, 8, 10. RESULTS: Median inflammatory compound levels were 1.2-2.3 times higher in cord vs. maternal blood, except IL2 (1.3 times lower). Multiple significant correlations existed between maternal vs. infant inflammatory compounds (range of r = 0.22-0.48). While relationships existed with blood nutrient levels, the most significant were identified in placenta where all nutrients (except δ-tocopherol) exhibited relationships with inflammatory compounds. Relationships between anti-inflammatory nutrients and proinflammatory compounds were primarily inverse. CONCLUSION: Inflammation is strongly correlated between mother-infant dyads. Fat-soluble nutrients have relationships with inflammatory compounds, suggesting nutrition is a modifiable factor. IMPACT: Mother and newborn inflammation status are strongly interrelated. Levels of fat-soluble nutrients in blood, but especially placenta, are associated with blood levels of proinflammatory and anti-inflammatory compounds in both mother and newborn infant. As fat-soluble nutrient levels are associated with blood inflammatory compounds, nutrition is a modifiable factor to modulate inflammation and improve perinatal outcomes.

Changes in lipid profiles of epileptic mouse model.

INTRODUCTION: Approximately 1% of the world's population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD's success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation. OBJECTIVES: The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy. METHODS: FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5). RESULTS: Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1-/-. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane. CONCLUSION: Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.

Omega-3 fatty acid intake and prevalent respiratory symptoms among U.S. adults with COPD.

BACKGROUND: Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and derivatives, play a key role in the resolution of inflammation. Higher intake has been linked to decreased morbidity in several diseases, though effects on respiratory diseases like COPD are understudied. METHODS: The National Health and Nutrition Examination Survey (NHANES), with a focus on dietary assessment, provides a unique opportunity to explore relationships between omega-3 intake and morbidity in respiratory diseases marked by inflammation in the United States (US) population. We investigated relationships between ALA or EPA + DHA intake and respiratory symptoms among US adults with COPD, as well as variation in relationships based on personal characteristics or exposures. RESULTS: Of 878 participants, mean age was 60.6 years, 48% were current smokers, and 68% completed high school. Omega-3 intake was, 1.71 ± 0.89 g (ALA), and 0.11 ± 0.21 g (EPA + DHA). Logistic regression models, adjusting for age, gender, race, body mass index, FEV1, education, smoking status, pack-years, total caloric intake, and omega-6 (linoleic acid, LA) intake demonstrated no primary associations between omega-3 intake and respiratory symptoms. Interaction terms were used to determine potential modification of relationships by personal characteristics (race, gender, education) or exposures (LA intake, smoking status), demonstrating that at lower levels of LA intake, increasing ALA intake was associated with reduced odds of chronic cough (pint = 0.015) and wheeze (pint = 0.037). EPA + DHA, but not ALA, was associated with reduced symptoms only among current smokers who did not complete high school. CONCLUSIONS: Individual factors should be taken into consideration when studying the association of fatty acid intake on respiratory diseases, as differential responses may reveal susceptible subgroups.

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities.

Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue.

Food Insecurity is Associated With COPD Morbidity and Perceived Stress.

Background: Low socioeconomic status (SES) has been associated with worse clinical outcomes in chronic obstructive pulmonary disease (COPD). Food insecurity is more common among individuals with low SES and has been associated with poor outcomes in other chronic illnesses, but its impact on COPD has not been studied. Methods: Former smokers with spirometry-confirmed COPD were recruited from low-income areas of Baltimore, Maryland, and followed for 9 months as part of a cohort study of diet and indoor air pollution. Food insecurity and respiratory outcomes, including COPD exacerbations and patient-reported outcomes, were assessed at regular intervals. The association between food insecurity and COPD outcomes was analyzed using generalized linear mixed models. Additional analyses examined the association of COPD morbidity with subdomains of food insecurity and the association of food insecurity with psychological well-being measures. Results: Ninety-nine participants had available data on food insecurity and COPD outcomes. A total of 26.3% of participants were food insecure at 1 or more times during the study. After adjusting for individual SES, neighborhood poverty, and low healthy food access, food insecurity was associated with a higher incidence rate of moderate and severe exacerbations and worse dyspnea, COPD health status, and respiratory-specific quality of life. Subdomains of food insecurity were independently associated with worse patient-reported outcomes. Food insecurity was additionally associated with higher perceived stress. Discussion: Among former smokers with COPD, food insecurity was associated with a higher incidence of exacerbations, worse patient-reported outcomes, and higher perceived stress. Subdomains of food insecurity were independently associated with worse patient-reported outcomes.

Something Smells Fishy: How Lipid Mediators Impact the Maternal-Fetal Interface and Neonatal Development.

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled inflammation can lead to poor maternal and infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and -6 fatty acids obtained through the diet are metabolized into bioactive compounds that effect inflammation. Recent evidence has shown that the downstream products of omega-3 and -6 fatty acids may influence physiology during pregnancy. In this review, the current knowledge relating to omega-3 and omega-6 metabolites during pregnancy will be summarized.

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative.

BACKGROUND: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. METHODS: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period. RESULTS: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures. CONCLUSIONS: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

QuPath Digital Immunohistochemical Analysis of Placental Tissue.

BACKGROUND: QuPath is an open-source digital image analyzer notable for its user-friendly design, cross-platform compatibility, and customizable functionality. Since it was first released in 2016, at least 624 publications have reported its use, and it has been applied in a wide spectrum of settings. However, there are currently limited reports of its use in placental tissue. Here, we present the use of QuPath to quantify staining of G-protein coupled receptor 18 (GPR18), the receptor for the pro-resolving lipid mediator Resolvin D2, in placental tissue. METHODS: Whole slide images of vascular smooth muscle (VSM) and extravillous trophoblast (EVT) cells stained for GPR18 were annotated for areas of interest. Visual scoring was performed on these images by trained and in-training pathologists, while QuPath scoring was performed with the methodology described herein. RESULTS: Bland-Altman analyses showed that, for the VSM category, the two methods were comparable across all staining levels. For EVT cells, the high-intensity staining level was comparable across methods, but the medium and low staining levels were not comparable. CONCLUSIONS: Digital image analysis programs offer great potential to revolutionize pathology practice and research by increasing accuracy and decreasing the time and cost of analysis. Careful study is needed to optimize this methodology further.

Association of Dietary Fiber on Asthma, Respiratory Symptoms, and Inflammation in the Adult National Health and Nutrition Examination Survey Population.

Rationale: High intake of dietary fiber may have antiinflammatory properties and be protective against respiratory morbidity.Objectives: We examined the relationship between dietary fiber intake and asthma, respiratory symptoms, and inflammation among adults who participated in the 2007 to 2012 NHANES (National Health and Nutrition Examination Survey).Methods: We analyzed data from adults 20 to 79 years of age (n = 13,147) with complete information on fiber intake, total calorie intake, body mass index, smoking status, and poverty level. Fiber intake was categorized into quartiles, with Q1 being lowest quartile of intake and Q4 being the highest quartile. Respiratory morbidities included asthma, wheeze, cough, and phlegm. Self-report questionnaires were used to define asthma, wheeze, cough, and phlegm production. Serum C-reactive protein (CRP) was used as a biomarker of inflammation. Exclusion criteria included current pregnancy and implausible intake of total calories.Results: A total of 69.5% of participants were non-Hispanic white; 54.5% were nonsmokers, and 7.8% had current asthma. After adjusting for covariates, fiber intake was associated with asthma (P = 0.01), with an increased odds of asthma with lower fiber intake (Q1 vs. Q4: odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-1.8; P = 0.027). There were significant interactions between fiber and sex and fiber and race/ethnicity; stronger associations were seen for women and for non-Hispanic white adults. Low fiber intake (Q1) was associated with increased odds of wheeze (OR, 1.3; 95% CI, 1.0-1.6; P = 0.018), cough (OR, 1.7; 95% CI, 1.2-2.3; P = 0.002), and phlegm (OR, 1.4; 95% CI, 1.1-2.0; P = 0.021) compared with high fiber intake. The odds of having high CRP versus nondetectable CRP were 1.6 times higher in the low-fiber group (Q1) compared with high-fiber group (Q4; OR, 1.6; 95% CI, 1.0-2.5).Conclusions: High-fiber diet may mediate an inflammatory response and decrease odds of having asthma, especially for women and specific racial groups, cough, wheeze, and phlegm production when compared with low-fiber diet.

Aberrant energy metabolism and redox balance in seizure onset zones of epileptic patients.

Epilepsy is a disorder that affects around 1% of the population. Approximately one third of patients do not respond to anti-convulsant drugs treatment. To understand the underlying biological processes involved in drug resistant epilepsy (DRE), a combination of proteomics strategies was used to compare molecular differences and enzymatic activities in tissue implicated in seizure onset to tissue with no abnormal activity within patients. Label free quantitation identified 17 proteins with altered abundance in the seizure onset zone as compared to tissue with normal activity. Assessment of oxidative protein damage by protein carbonylation identified additional 11 proteins with potentially altered function in the seizure onset zone. Pathway analysis revealed that most of the affected proteins are involved in energy metabolism and redox balance. Further, enzymatic assays showed significantly decreased activity of transketolase indicating a disruption of the Pentose Phosphate Pathway and diversion of intermediates into purine metabolic pathway, resulting in the generation of the potentially pro-convulsant metabolites. Altogether, these findings suggest that imbalance in energy metabolism and redox balance, pathways critical to proper neuronal function, play important roles in neuronal network hyperexcitability and can be used as a primary target for potential therapeutic strategies to combat DRE. SIGNIFICANCE: Epileptic seizures are some of the most difficult to treat neurological disorders. Up to 40% of patients with epilepsy are resistant to first- and second-line anticonvulsant therapy, a condition that has been classified as refractory epilepsy. One potential therapy for this patient population is the ketogenic diet (KD), which has been proven effective against multiple refractory seizure types However, compliance with the KD is extremely difficult, and carries severe risks, including ketoacidosis, renal failure, and dangerous electrolyte imbalances. Therefore, identification of pathways disruptions or shortages can potentially uncover cellular targets for anticonvulsants, leading to a personalized treatment approach depending on a patient's individual metabolic signature.

Insufficient zinc intake enhances lung inflammation in response to agricultural organic dust exposure.

Organic dust exposure particularly within hog confinement facilities is a significant cause of airway inflammation and lung disease. In a cohort of Midwestern veterans with COPD and agricultural work exposure we observed reduced zinc intakes which were associated with decreased lung function. Because insufficient zinc intake is common within the U.S. and a potent modulator of innate immune function, we sought to determine whether deficits in zinc intake would impact the airway inflammatory response to hog confinement facility dust extract (HDE). Adult male C57BL/6 mice were randomized to zinc deficient or matched zinc sufficient diets for 3 weeks and subsequently treated with intranasal HDE inhalation or saline once or daily for 3 weeks while maintained on specific diets. Lavage fluid and lung tissue was collected. Conditions of zinc deficiency were also studied in macrophages exposed to HDE. Single and repetitive HDE inhalation exposure resulted in increased influx of total cells and neutrophils, increased mediator hyper-responsiveness (TNFα, IL-6, CXCL1, and amphiregulin), and enhanced tissue pathology that was more pronounced in zinc deficient mice compared to normal dietary counterparts. Airway inflammation was most pronounced in zinc deficient mice treated with repetitive HDE for 3 weeks. Similarly, macrophages maintained in a zinc deficient environment exhibited increased CXCL1 and IL-23 production as a result of increased NF-κB activation. Conclusion: Given the relatively high incidence of dietary deficiencies in agriculture workers, we anticipate that zinc intake, or a lack thereof, may play an important role in modulating the host response to organic dust exposure.

A Qualitative Study of Experiences of Participants in Cardiac Rehabilitation.

PURPOSE: Maintenance of lifestyle changes after cardiac rehabilitation (CR) is suboptimal. In addition, partners of cardiac patients are invited to participate in CR educational sessions and implicitly expected to assist patients with their lifestyle changes. The purpose of this study was to qualitatively examine patient and partner perceptions of phase 2 CR 3 mo after completion of the program. METHODS: A purposive sample of 11 couples (patients post-heart surgery and their spouses) was interviewed following completion of CR. Semistructured, in-person interviews were conducted with patients and spouses separately. Data were analyzed using line-by-line coding to identify themes. RESULTS: Themes were identified in relation to program elements of CR. Exercise themes were as follows: (1) benefitted from exercise and (2) felt held back. Education themes were as follows: (1) received basic education and (2) needed more personalized information. CR environment themes were as follows: (1) developed confidence; (2) made social comparisons; and (3) helped to have partner there. CONCLUSION: Overall, participant perceptions of exercise, education, and the CR environment were very positive. Nevertheless, there is a need to improve educational efforts within CR to rely less on "canned" presentations and more on participants developing their own self-management methods to maintain a healthy lifestyle after CR.

Promotion of lung health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases.

Lung-related research primarily focuses on the etiology and management of diseases. In recent years, interest in primary prevention has grown. However, primary prevention also includes "health promotion" (actions in a population that keep an individual healthy). We encourage more research on population-based (public health) strategies that could not only maximize lung health but also mitigate "normal" age-related declines-not only for spirometry but across multiple measures of lung health. In developing a successful strategy, a "life course" approach is important. Unfortunately, we are unable to achieve the full benefit of this approach until we have better measures of lung health and an improved understanding of the normal trajectory, both over an individual's life span and possibly across generations. We discuss key questions in lung health promotion, with an emphasis on the upper (healthier) end of the distribution of lung functioning and resiliency and briefly summarize the few interventions that have been studied to date. We conclude with suggestions regarding the most promising future research for this important, but largely neglected, area of lung research.

Prevalence of metabolic syndrome in COPD patients and its consequences.

BACKGROUND: The prevalence of metabolic syndrome in COPD patients and its impact on patient related outcomes has been little studied. We evaluated the prevalence of metabolic syndrome and clinical and functional characteristics in patients with COPD and healthy subjects. METHODS: 228 COPD patients and 156 healthy subjects were included. Metabolic syndrome was defined using criteria of the IDF. In all patients spirometry, body composition, functional exercise performance, and mood and health status were assessed. Groups were stratified for BMI and gender. RESULTS: Metabolic syndrome was present in 57% of the COPD patients and 40% of the healthy subjects. After stratification for BMI, presence of metabolic syndrome in patients with a BMI ≥25 kg/m2 was higher than in healthy peers. Patients with metabolic syndrome and a BMI <25 kg/m2 had higher BMI, fat free mass index and bone mineral density, and a lower 6MWD than the BMI matched patients without metabolic syndrome. Spirometry, maximal ergometry, mood and health status, and blood gases were not different between those groups. In COPD patients with metabolic syndrome self-reported co-morbidities and medication use were higher than in those without. CONCLUSION: Metabolic syndrome is more prevalent in overweight or obese COPD patients than in BMI matched healthy subjects. Metabolic syndrome did not additionally impact patients' functional outcomes, but did impact the prevalence of co-morbidities.

Demographics and nutrition-related patient care encounters: a survey of physician assistants in Nebraska.

PURPOSE: To collect information regarding demographics, nutrition-related patient care encounters, and comfort levels in addressing nutrition-related problems in a population of physician assistants (PA) currently practicing in Nebraska. METHODS: A survey was developed by faculty members in the Medical Nutrition Education and Physician Assistant Education programs, School of Allied Health Professions, College of Medicine, University of Nebraska Medical Center. Data were analyzed using descriptive statistics and Fisher's exact test. A P-value of < .05 was considered statistically significant. RESULTS: The return rate of the survey was 70% (N = 266). A high percentage of PAs (86%) reported they often or occasionally encounter nutrition-related issues with patients. In contrast, only 27% of survey respondents felt "very comfortable" in addressing nutrition-related issues. Encountering nutrition issues often and having patients that ask questions about nutrition were significantly associated with a PA's comfort in addressing nutrition issues (P < .001 for both). CONCLUSION: PAs are very likely to encounter nutrition-related issues in their practice. Attention to nutrition-related topics in the PA curriculum and continuing education may be beneficial in increasing the comfort of PAs in addressing these issues.