Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.

US Immigration Westernizes the Human Gut Microbiome.

Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations.

Update on Immunotherapy Cardiotoxicity: Checkpoint Inhibitors, CAR T, and Beyond.

OPINION STATEMENT: Immunotherapy is an innovative approach to cancer treatment that involves using the body's immune system to fight cancer. The landscape of immunotherapy is constantly evolving, as new therapies are developed and refined. Some of the most promising approaches in immunotherapy include immune checkpoint inhibitors (ICIs): these drugs target proteins on the surface of T-cells that inhibit their ability to attack cancer cells. By blocking these proteins, checkpoint inhibitors allow T-cells to recognize and destroy cancer cells more effectively. CAR T-cell therapy: this therapy involves genetically modifying a patient's own T-cells to recognize and attack cancer cells. CAR T-cell therapy exhibits favorable response in many patients with refractory hematological cancers with growing clinical trials in solid tumors. Immune system modulators: these drugs enhance the immune system's ability to fight cancer by stimulating the production of immune cells or inhibiting the activity of immune-suppressing cells. While immunotherapy has shown great promise in the treatment of cancer, it can also pose significant cardiac side effects. Some immunotherapy drugs like ICIs can cause myocarditis, which can lead to chest pain, shortness of breath, and heart failure. Other cardiac side effects of ICIs include arrhythmias, pericarditis, vasculitis, and accelerated atherosclerosis. It is important for patients receiving immunotherapy to be monitored closely for these side effects, as prompt treatment can help prevent serious complications. Patients should also report any symptoms to their healthcare providers right away, so that appropriate action can be taken. CAR T-cell therapy can also illicit an exaggerated immune response creating cytokine release syndrome (CRS) that may precipitate cardiovascular events: arrhythmias, myocardial infarction, and heart failure. Overall, while immune modulating therapy is a promising and expanding approach to cancer treatment, it is important to weigh the potential benefits against the risks and side effects, especially in patients with high risk for cardiovascular complications.

Multi-Omics Analyses Show Disease, Diet, and Transcriptome Interactions With the Virome.

BACKGROUND & AIMS: The gut virome includes eukaryotic viruses and bacteriophages that can shape the gut bacterial community and elicit host responses. The virome can be implicated in diseases, such as irritable bowel syndrome (IBS), where gut bacteria play an important role in pathogenesis. We provide a comprehensive and longitudinal characterization of the virome, including DNA and RNA viruses and paired multi-omics data in a cohort of healthy subjects and patients with IBS. METHODS: We selected 2 consecutive stool samples per subject from a longitudinal study cohort and performed metagenomic sequencing on DNA and RNA viruses after enriching for viral-like particles. Viral sequence abundance was evaluated over time, as well as in the context of diet, bacterial composition and function, metabolite levels, colonic gene expression, host genetics, and IBS subsets. RESULTS: We found that the gut virome was temporally stable and correlated with the colonic transcriptome. We identified IBS-subset-specific changes in phage populations; Microviridae, Myoviridae, and Podoviridae species were elevated in diarrhea-predominant IBS, and other Microviridae and Myoviridae species were elevated in constipation-predominant IBS compared to healthy controls. We identified correlations between subsets of the virome and bacterial composition (unclassifiable "dark matter" and phages) and diet (eukaryotic viruses). CONCLUSIONS: We found that the gut virome is stable over time but varies among subsets of patients with IBS. It can be affected by diet and potentially influences host function via interactions with gut bacteria and/or altering host gene expression.

A Guide to Dietary Pattern-Microbiome Data Integration.

The human gut microbiome is linked to metabolic and cardiovascular disease risk. Dietary modulation of the human gut microbiome offers an attractive pathway to manipulate the microbiome to prevent microbiome-related disease. However, this promise has not been realized. The complex system of diet and microbiome interactions is poorly understood. Integrating observational human diet and microbiome data can help researchers and clinicians untangle the complex systems of interactions that predict how the microbiome will change in response to foods. The use of dietary patterns to assess diet-microbiome relations holds promise to identify interesting associations and result in findings that can directly translate into actionable dietary intake recommendations and eating plans. In this article, we first highlight the complexity inherent in both dietary and microbiome data and introduce the approaches generally used to explore diet and microbiome simultaneously in observational studies. Second, we review the food group and dietary pattern-microbiome literature focusing on dietary complexity-moving beyond nutrients. Our review identified a substantial and growing body of literature that explores links between the microbiome and dietary patterns. However, there was very little standardization of dietary collection and assessment methods across studies. The 54 studies identified in this review used ≥7 different methods to assess diet. Coupled with the variation in final dietary parameters calculated from dietary data (e.g., dietary indices, dietary patterns, food groups, etc.), few studies with shared methods and assessment techniques were available for comparison. Third, we highlight the similarities between dietary and microbiome data structures and present the possibility that multivariate and compositional methods, developed initially for microbiome data, could have utility when applied to dietary data. Finally, we summarize the current state of the art for diet-microbiome data integration and highlight ways dietary data could be paired with microbiome data in future studies to improve the detection of diet-microbiome signals.

Characterisation, procedures and heritability of acute dietary intake in the Twins UK cohort: an observational study.

BACKGROUND: Estimated food records (EFR) are a common dietary assessment method. This investigation aimed to; (1) define the reporting quality of the EFR, (2) characterise acute dietary intake and eating behaviours, (3) describe diet heritability. METHODS: A total of 1974 one-day EFR were collected from 1858 participants in the TwinsUK cohort between 2012 and 2017. EFR were assessed using a six-point scoring system to determine reporting quality. The frequency and co-occurrence of food items was examined using word clouds and co-occurrence networks. The impact of eating behaviours on weight, BMI and nutrient intake were explored using mixed-effect linear regression models. Finally, diet heritability was estimated using ACE modelling. RESULTS: We observed that 75% of EFR are of acceptable reporting quality (score > 5). Black tea and semi-skimmed milk were the most consumed items, on an individual basis (respectively 8.27, 6.25%) and paired (0.21%) as co-occurring items. Breakfast consumption had a significantly (p = 5.99 × 10- 7) greater impact on energy (kcal) (mean 1874.67 (±SD 532.42)) than skipping breakfast (1700.45 (±SD 620.98)), however only length of eating window was significantly associated with body weight (kg) (effect size 0.21 (±SD 0.10), p = 0.05) and BMI (effect size 0.08 (±SD 0.04), p = 0.04) after adjustment for relevant covariates. Lastly, we reported that both length of eating window (h2 = 33%, CI 0.24; 0.41), and breakfast consumption (h2 = 11%, CI 0.02; 0.21) were weakly heritable. CONCLUSIONS: EFR describing acute dietary intake allow for eating behaviour characterisation and can supplement habitual diet intake assessments. Novel findings of heritability warrant further investigation.

Evaluating the Feasibility and Efficacy of a Pediatric Intensive Care Unit Diary.

As the progress of critical care medicine has improved the survival rate of critically ill patients, comorbidities and long-term health care have attracted people's attention. The terms "post-intensive care syndrome" (PICS) and "PICS-family" (PICS-F) have been used in non-neurocritical care populations, which are characterized by the cognitive, psychiatric, and physical sequelae associated with intensive care hospitalization of survivors and their families. An intensive care unit (ICU) diary authored by the patient's family members may alleviate the psychological distress of the patient and his or her family. This quality improvement project focused on the development and implementation of the pediatric intensive care unit (PICU) diary in the pediatric critical care setting. The project aims to evaluate the feasibility and the potential efficacy of the PICU diary, measured through parental acceptance and satisfaction. Seventeen families of critically ill children admitted to the PICU received the PICU diary during the implementation period. Twenty-four parents completed the weekly follow-up, and 15 subsequently completed the diary entry evaluation. The use of the diary in the PICU setting is feasible and considered beneficial by families of critically ill children.

Microbial metabolism and adaptations in Atribacteria-dominated methane hydrate sediments.

Gas hydrates harbour gigatons of natural gas, yet their microbiomes remain understudied. We bioprospected 16S rRNA amplicons, metagenomes, and metaproteomes from methane hydrate-bearing sediments under Hydrate Ridge (offshore Oregon, USA, ODP Site 1244, 2-69 mbsf) for novel microbial metabolic and biosynthetic potential. Atribacteria sequences generally increased in relative sequence abundance with increasing sediment depth. Most Atribacteria ASVs belonged to JS-1-Genus 1 and clustered with other sequences from gas hydrate-bearing sediments. We recovered 21 metagenome-assembled genomic bins spanning three geochemical zones in the sediment core: the sulfate-methane transition zone, the metal (iron/manganese) reduction zone, and the gas hydrate stability zone. We found evidence for bacterial fermentation as a source of acetate for aceticlastic methanogenesis and as a driver of iron reduction in the metal reduction zone. In multiple zones, we identified a Ni-Fe hydrogenase-Na+ /H+ antiporter supercomplex (Hun) in Atribacteria and Firmicutes bins and in other deep subsurface bacteria and cultured hyperthermophiles from the Thermotogae phylum. Atribacteria expressed tripartite ATP-independent transporters downstream from a novel regulator (AtiR). Atribacteria also possessed adaptations to survive extreme conditions (e.g. high salt brines, high pressure and cold temperatures) including the ability to synthesize the osmolyte di-myo-inositol-phosphate as well as expression of K+ -stimulated pyrophosphatase and capsule proteins.

Nutrient comparisons of margarine/margarine-like products, butter blend products and butter in the US marketplace in 2020 post-FDA ban on partially hydrogenated oils.

OBJECTIVE: To evaluate the fatty acid profiles and relevant vitamin and mineral compositions of margarine/margarine-like products and butter blend products available in the US marketplace and to compare with butter. DESIGN: Analysis of the food and nutrient composition information available for margarine/margarine-like products, butter blend products and butter in the 2021 version of the University of Minnesota Nutrition Coordinating Center (NCC) Food and Nutrient Database. SETTING: The US retail food marketplace in 2020. PARTICIPANTS: A selection of eighty-three margarine/margarine-like or butter blend products available in the USA in 2020 and regular and whipped butter (both salted and unsalted). RESULTS: All products contained no or negligible amounts of trans fat. Mean daily values (DV) for SFA per 1 tablespoon ranged from 11 % for margarine/margarine-like tub and squeeze products to 18 % for margarine/margarine-like stick products and butter blend products. In contrast, one tablespoon butter provides 36 % of the DV for SFA. Results from ANOVA comparing the percent of total fat from SFA, PUFA and MUFA by product type indicated significant differences for SFA (P < 0·01) and PUFA (P < 0·01), but not MUFA (P = 0·07). CONCLUSIONS: Leading brands of margarine/margarine-like and butter blend products examined in this study were found to be in greater alignment with current dietary recommendations for fatty acids and cholesterol than butter. Margarine/margarine-like tub and squeeze products were found to be optimal over margarine/margarine-like stick products and butter blend products. Future research should include an examination of private label products.

The Feasibility of Using Comic-Based Concussion Discharge Instructions: Gauging Likeability and Knowledge Improvement Among Adolescents and Parents.

OBJECTIVE: The objective of this study was to evaluate feasibility of supplementing emergency department (ED) concussion discharge instructions for adolescents and parents with a newly created educational comic and a publicly available comic-based video at an outpatient sports neurology clinic. METHODS: We created a gender-neutral, 2-page comic to augment text-only ED concussion discharge instructions. A sample of patients evaluated at a sports neurology clinic and their parents/guardians participated. Patients and their parents were randomized to view either the comic only or both the comic and publicly available comic-based video. Patients and parents completed preintervention and postintervention surveys to assess likeability and concussion knowledge including concussion definition, symptoms, return-to-ED criteria, and resuming normal activity. Data were analyzed using descriptive and comparative statistics. RESULTS: A total of 57 patients (47.4% female; mean age, 15 years) and 37 guardians were enrolled. Most (73%) concussions were sports related, with the majority having sought care within 24 hours in an ED (80%). Over half (51%) had experienced 2 or more prior concussions. Overall, 31 adolescents and 20 guardians viewed both comic and video, whereas 26 adolescents and 17 guardians viewed the comic only. Both comic and video were favorably reviewed, but a higher proportion of respondents rated the video more positively than the comic for likability (P < 0.01), comprehensibility (P < 0.05), and increasing understanding (P < 0.05). Patients' knowledge of some concussion symptoms emphasized in the comic increased after reading (emotional changes, P = 0.02; vomiting, P = 0.04). CONCLUSIONS: Patients showed increased concussion knowledge using the favorably endorsed comic-based discharge instructions. Using comic-based supplemental discharge tools may optimize concussion education for adolescents.

Genetic and phenotypic associations between root architecture, arbuscular mycorrhizal fungi colonisation and low phosphate tolerance in strawberry (Fragaria × ananassa).

BACKGROUND: Phosphate is an essential plant macronutrient required to achieve maximum crop yield. Roots are able to uptake soil phosphate from the immediate root area, thus creating a nutrient depletion zone. Many plants are able to exploit phosphate from beyond this root nutrient depletion zone through symbiotic association with Arbuscular Mycorrhizal Fungi (AMF). Here we characterise the relationship between root architecture, AMF association and low phosphate tolerance in strawberries. The contrasting root architecture in the parental strawberry cultivars 'Redgauntlet' and 'Hapil' was studied through a mapping population of 168 progeny. Low phosphate tolerance and AMF association was quantified for each genotype to allow assessment of the phenotypic and genotypic relationships between traits. RESULTS: A "phosphate scavenging" root phenotype where individuals exhibit a high proportion of surface lateral roots was associated with a reduction in root system size across genotypes. A genetic correlation between "root system size" traits was observed with a network of pleiotropic QTL found to represent five "root system size" traits. By contrast, average root diameter and the distribution of roots appeared to be under two discrete methods of genetic control. A total of 18 QTL were associated with plant traits, 4 of which were associated with solidity that explained 46% of the observed variation. Investigations into the relationship between AMF association and root architecture found that a higher root density was associated with greater AMF colonisation across genotypes. However, no phenotypic correlation or genotypic association was found between low phosphate tolerance and the propensity for AMF association, nor root architectural traits when plants are grown under optimal nutrient conditions. CONCLUSIONS: Understanding the genetic relationships underpinning phosphate capture can inform the breeding of strawberry varieties with better nutrient use efficiency. Solid root systems were associated with greater AMF colonisation. However, low P-tolerance was not phenotypically or genotypically associated with root architecture traits in strawberry plants. Furthermore, a trade-off was observed between root system size and root architecture type, highlighting the energetic costs associated with a "phosphate scavenging" root architecture.

Contralateral HeRO Graft Insertion to Treat Severe Venous Hypertension and Preserve Arteriovenous Fistula Patency.

BACKGROUND: Central venous stenosis and occlusion (CVO) is an increasing problem in the growing hemodialysis population. Sequelae include loss of access, loss of sites suitable for future venous access, and venous hypertension. Endoluminal techniques are often unsuitable to treat long-standing stenoses, and open surgery confers higher morbidity and is not appropriate in many patients. CASE: We present a case of long-standing central venous stenosis with an ipsilateral functioning fistula but with significant symptoms and signs of venous hypertension. The stenosis was not considered appropriate for endoluminal treatment, and the patient was considered to be at too high risk for open surgery. The Hemodialysis Reliable Outflow (HeRO) (Merit Medical Systems, UT) device was used to bypass the fistula to the superior vena cava via the contralateral internal jugular vein. CONCLUSIONS: This case demonstrates the utility of the HeRO device in cases of long-standing CVO necessitating contralateral bypass. This technique confers the benefits of open surgery while minimizing the associated risks.

Dietary intake and micronutrient deficiency in children with cancer.

Data regarding micronutrient deficiencies in children with cancer are lacking. We measured micronutrients in a subset of children with cancer (n = 23) participating in a randomized trial of the neutropenic diet. Ninety-six percent of children had ≥1 micronutrient deficiency and 39% had ≥3 micronutrient deficiencies. Eighty-six percent of children had vitamin C deficiency, 87% had 25-hydroxyvitamin D deficiency, 50% had zinc deficiency, and 13% had vitamin A deficiency. Dietary intake did not correlate with micronutrient deficiency status. More data are needed regarding the prevalence and etiology of micronutrient deficiencies in children with cancer to further understand their implications and treatment.

School Practices to Foster LGBT-Supportive Climate: Associations with Adolescent Bullying Involvement.

Lesbian, gay, bisexual, and transgender (LGBT) youth experience disproportionate rates of bullying compared to their heterosexual peers. Schools are well-positioned to address these disparities by creating supportive school climates for LGBT youth, but more research is needed to examine the variety of practices and professional development opportunities put in place to this end. The current study examines how school practices to create supportive LGBT student climate relate to student reports of bullying. Student-level data come from the 2013 Minnesota Student Survey, a state-wide survey of risk and protective factors. Ninth and eleventh grade students (N = 31,183) reported on frequency of physical and relational bullying victimization and perpetration and sexual orientation-based harassment. School administrators reported on six practices related to creating supportive LGBT school climate (N = 103 schools): having a point person for LGBT student issues, displaying sexual orientation-specific content, having a gay-straight alliance, discussing bullying based on sexual orientation, and providing professional development around LGBT inclusion and LGBT student issues. An index was created to indicate how many practices each school used (M = 2.45; SD = 1.76). Multilevel logistic regressions indicated that students attending schools with more supportive LGBT climates reported lower odds of relational bullying victimization, physical bullying perpetration, and sexual orientation-based harassment compared to students in schools with less supportive LGBT climates. Sexual orientation did not moderate these relations, indicating that LGBT-supportive practices may be protective for all students, regardless of their sexual orientation. Findings support school-wide efforts to create supportive climates for LGBQ youth as part of a larger bullying prevention strategy.

Dietary pattern and diversity analysis using DietDiveR in R: a cross-sectional evaluation in the National Health and Nutrition Examination Survey.

BACKGROUND: There are few resources available for researchers aiming to conduct 24-h dietary record and recall analysis using R. OBJECTIVES: We aimed to develop DietDiveR, which is a toolkit of functions written in R for the analysis of recall or record data collected with the Automated Self-Administered 24-h Dietary Assessment Tool or 2-d 24-h dietary recall data from the National Health and Nutrition Examination Survey (NHANES). The R functions are intended for food and nutrition researchers who are not computational experts. METHODS: DietDiveR provides users with functions to 1) clean dietary data, 2) analyze 24-h dietary intakes in relation to other study-specific metadata variables, 3) visualize percentages of energy intake from macronutrients, 4) perform principal component analysis or k-means clustering to group participants by similar data-driven dietary patterns, 5) generate foodtrees based on the hierarchical food group information for food items consumed, 6) perform principal coordinate analysis taking food grouping information into account, and 7) calculate diversity metrics for overall diet and specific food groups. DietDiveR includes a self-paced tutorial on a website (https://computational-nutrition-lab.github.io/DietDiveR/). As a demonstration, we applied DietDiveR to a demonstration data set and data from NHANES 2015-2016 to derive a dietary diversity measure of nuts, seeds, and legumes consumption. RESULTS: Adult participants in the NHANES 2015-2016 cycle were grouped depending on the diversity in their mean consumption of nuts, seeds, and legumes. The group with the highest diversity in nuts, seeds, and legumes consumption had 3.8 cm lower waist circumference (95% confidence interval: 1.0, 6.5) than those who did not consume nuts, seeds, and legumes. CONCLUSIONS: DietDiveR enables users to visualize dietary data and conduct data-driven dietary pattern analyses using R to answer research questions regarding diet. As a demonstration of this toolkit, we explored the diversity of nuts, seeds, and legumes consumption to highlight some of the ways DietDiveR can be used for analyses of dietary diversity.

Assessing the nutrient content of plant-based milk alternative products available in the U.S.

BACKGROUND: Consumption of plant-based milk alternatives is increasing. Current dietary guidance primarily relies on dairy milk as a source of key nutrients of public health concern including calcium and vitamin D. OBJECTIVE: To compare the nutritional content of plant-based milk alternatives between categories (e.g., soy, almond, and oat) and with dairy milk. DESIGN: This study presents an evaluation of the nutritional content of 219 plant-based milk alternatives from 21 brands available in the US marketplace using data from the University of Minnesota Nutrition Coordinating Center's (NCC) database. MAIN OUTCOME MEASURES: Nutrients of focus include those identified as nutrients of public health concern in the Dietary Guidelines for American's (DGA) or used by the United States Department of Agriculture (USDA) as criteria for determining whether a plant-based milk is a suitable substitute for dairy milk. STATISTICAL ANALYSES PERFORMED: Most data are presented as percent Daily Values (% DV). Nutrients and food components were compared using means, medians, interquartile ranges (IQR), and ranges. Statistical tests for significance were not used to evaluate between category differences because the plant-based milk alternatives included are a full census of the products from 21 brands available in the marketplace. Because data are a census, differences can be understood to be true differences. RESULTS: Fortified soy-based products most closely mimic the nutrient content of dairy milk. High variability was present in all the nutrients and food components. Plant-based milk alternatives were generally lower in protein and saturated fatty acids than dairy milk, with high variability in added sugars content. Approximately 70% were fortified with both calcium and vitamin D. CONCLUSIONS: These results indicate that most plant-based milk alternative products are not nutritionally equivalent to dairy milk, and there is high nutritional variability between and within product types. These findings highlight the importance of communicating the nutritional differences between plant-based milk alternatives and dairy milk to consumers.

Emergency preparedness for mass casualty events: South Texas commentary on the development of a statewide emergency response system.

Mass casualty incidents (MCIs) are on the rise in the USA, and hemorrhage is the leading cause of preventable death in trauma. The need for rapid access to life-saving blood and blood products is essential for preventing death due to hemorrhage. It is well established that most major cities in the USA are underprepared to meet blood transfusion requirements in the event of an MCI. The South Texas Whole Blood Consortium sought to rectify this and vowed to be prepared to provide low-titer type O-positive whole blood (LTOWB) and blood components to the people who need it, where and when they need it. This system was able to transport 25 units of LTOWB and packed red blood cells almost 100 miles away to Uvalde Memorial Hospital within just 67 minutes after notification of an active shooter. The regional consortium has created a pool of dedicated LTOWB donors affectionately called Heroes in Arms who can be called on to instantly augment locoregional blood supply. Previously pregnant women have historically been excluded from donating plasma and LTOWB due to the increased rates of human leukocyte antigen (HLA) antibody (Ab) positivity, which is associated with transfusion-related acute lung injury. However, the South Texas Blood and Tissue Center in San Antonio had a large number of qualified, previously pregnant females desire to join the Heroes in Arms program prompting them to assess the feasibility of providing HLA Ab testing for this demographic and the results were promising. This is the first report of previously pregnant women being included in the pool for donation of LTOWB.