Methods in Nutrition & Gut Microbiome Research: An American Society for Nutrition Satellite Session [13 October 2022].

The microbial cells colonizing the human body form an ecosystem that is integral to the regulation and maintenance of human health. Elucidation of specific associations between the human microbiome and health outcomes is facilitating the development of microbiome-targeted recommendations and treatments (e.g., fecal microbiota transplant; pre-, pro-, and post-biotics) to help prevent and treat disease. However, the potential of such recommendations and treatments to improve human health has yet to be fully realized. Technological advances have led to the development and proliferation of a wide range of tools and methods to collect, store, sequence, and analyze microbiome samples. However, differences in methodology at each step in these analytic processes can lead to variability in results due to the unique biases and limitations of each component. This technical variability hampers the detection and validation of associations with small to medium effect sizes. Therefore, the American Society for Nutrition (ASN) Nutritional Microbiology Group Engaging Members (GEM), sponsored by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), hosted a satellite session on methods in nutrition and gut microbiome research to review currently available methods for microbiome research, best practices, as well as tools and standards to aid in comparability of methods and results. This manuscript summarizes the topics and research discussed at the session. Consideration of the guidelines and principles reviewed in this session will increase the accuracy, precision, and comparability of microbiome research and ultimately the understanding of the associations between the human microbiome and health.

"The DEA would come in and destroy you": a qualitative study of fear and unintended consequences among opioid prescribers in WV.

BACKGROUND: West Virginia has one of the highest rates of opioid overdose related deaths and is known as the epicenter of the opioid crisis in the United States. In an effort to reduce opioid-related harms, SB 273 was signed in 2018, and aimed to restrict opioid prescribing in West Virginia. SB 273 was enacted during a time when physician arrests and convictions had been increasing for years and were becoming more prevalent and more publicized. This study aims to better understand the impact of the legislation on patients and providers. METHODS: Twenty semi-structured interviews were conducted with opioid-prescribing primary care physicians and specialists practicing throughout West Virginia. RESULTS: Four themes emerged, 1. Fear of disciplinary action, 2. Exacerbation of opioid prescribing fear due to restrictive legislation, 3. Care shifts and treatment gaps, and 4. Conversion to illicit substances. The clinicians recognized the harms of inappropriate prescribing and how this could affect their patients. Decreases in opioid prescribing were already occurring prior to the law implementation. Disciplinary actions against opioid prescribers resulted in prescriber fear, which was then exacerbated by SB 273 and contributed to shifts in care that led to forced tapering and opioid under-prescribing. Providers felt that taking on patients who legitimately required opioids could jeopardize their career. CONCLUSION: A holistic and patient-centered approach should be taken by legislative and disciplinary bodies to ensure patients are not abandoned when disciplinary actions are taken against prescribers or new legislation is passed.

Very-low-protein diets lead to reduced food intake and weight loss, linked to inhibition of hypothalamic mTOR signaling, in mice.

The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or 20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.

Of Mice and Men: Impacts of Calorie Restriction on Metabolomics of the Cerebellum.

The main purpose of research in mice is to explore metabolic changes in animal models and then predict or propose potential translational benefits in humans. Although some researchers in the brain research field have mentioned that the mouse experiments results still lack the complex neuroanatomy of humans, caution is required to interpret the findings. In mice, we observed in article seventeenth of the series of the effects of graded levels of calorie restriction, metabolomic changes in the cerebellum indicated activation of hypothalamocerebellar connections driven by hunger responses. Therefore, the purpose of the current perspective is to set this latest paper into a wider context of the physiological, behavioral, and molecular changes seen in these mice and to compare and contrast them with previous human studies.

The Effects of Graded Levels of Calorie Restriction: XVI. Metabolomic Changes in the Cerebellum Indicate Activation of Hypothalamocerebellar Connections Driven by Hunger Responses.

Calorie restriction (CR) remains the most robust intervention to extend life span and improve healthspan. Though the cerebellum is more commonly associated with motor control, it has strong links with the hypothalamus and is thought to be associated with nutritional regulation and adiposity. Using a global mass spectrometry-based metabolomics approach, we identified 756 metabolites that were significantly differentially expressed in the cerebellar region of the brain of C57BL/6J mice, fed graded levels of CR (10, 20, 30, and 40 CR) compared to mice fed ad libitum for 12 hours a day. Pathway enrichment indicated changes in the pathways of adenosine and guanine (which are precursors of DNA production), aromatic amino acids (tyrosine, phenylalanine, and tryptophan) and the sulfur-containing amino acid methionine. We also saw increases in the tricarboxylic acid cycle (TCA) cycle, electron donor, and dopamine and histamine pathways. In particular, changes in l-histidine and homocarnosine correlated positively with the level of CR and food anticipatory activity and negatively with insulin and body temperature. Several metabolic and pathway changes acted against changes seen in age-associated neurodegenerative disorders, including increases in the TCA cycle and reduced l-proline. Carnitine metabolites contributed to discrimination between CR groups, which corroborates previous work in the liver and plasma. These results indicate the conservation of certain aspects of metabolism across tissues with CR. Moreover, this is the first study to indicate CR alters the cerebellar metabolome, and does so in a graded fashion, after only a short period of restriction.

Live discharge from hospice care: psychosocial challenges and opportunities.

Hospice social workers face many challenges in attempts to replicate or supplement the holistic support and unique services hospice provides for individuals discharged alive. This discontinuity in care can impact the types of supports needed by individuals and caregivers, which may or may not be accessible within their community. Patients and families who have access to community-based palliative care programs following a discharge generally tend to navigate the process with fewer challenges. This qualitative study (N = 24) explored both the challenges of the live discharge process and the opportunities within social work practice in the US. Results from this study emphasize the need for a framework to better approach a live discharge to ensure appropriate supports are accessible for all patients and caregivers. Specifically, results highlight both the concrete and psychosocial challenges in live discharges as a result of tension between current eligibility requirements and individual feelings and needs. Social workers also provided suggestions to improve the live discharge process, including attention to communication and preparation. This paper outlines specific challenges of live discharge from hospice, a framework for understanding presented challenges, and implications for policy and practice.

Multivitamins and Nutritional Adequacy in Middle-Aged to Older Americans by Obesity Status.

Multivitamins are the most commonly consumed dietary supplement in the United States and worldwide. Micronutrient insufficiency and clinical deficiency are more common in middle-aged to older adults, and multivitamin use has been shown to improve status in this population. This analysis aimed to assess contributions of sporadic and consistent multivitamin use to total usual micronutrient intakes and associated nutritional biomarkers among middle-aged to older US adults age ≥51 years, stratified by obesity status. Self-reported dietary intake and laboratory measures from the National Health and Nutrition Examination Survey were used in these analyses. The National Cancer Institute method was used to assess usual intakes of 18 micronutrients. Compared with food alone, multivitamin use was associated with a lower prevalence of inadequacies and improved nutritional biomarker status for folate, iodine, selenium, and vitamins B6, B12, and D. Consistent use decreased the prevalence of inadequacy for most micronutrients assessed, except for those micronutrients typically not found (or in miniscule amounts) in standard multivitamin products. In addition to a lower prevalence of inadequacy for many micronutrients associated with consistent use of multivitamins, sporadic use decreased the prevalence of inadequacy for a greater number of micronutrients in obese versus nonobese individuals. Multivitamin use (sporadic and consistent) also increased the proportion of individuals who exceeded the tolerable upper intake level for folic acid to 8%-10%. Nutritional biomarker data indicate that obese individuals may be at greater risk of clinical deficiency in vitamins B6 and D. Use of gender- and age-specific multivitamins may serve as a practical means to increase micronutrient status and decrease prevalences of clinical deficiency in the middle-aged to older population, particularly in those who are obese.

Nutritional Intake and Bone Health Among Adults With Probable Undiagnosed, Untreated Celiac Disease: What We Eat in America and NHANES 2009-2014.

Objective: The aim was to evaluate differences in nutritional intake of calcium, vitamin D, and phosphorus; serologic indices of these nutrients; and bone health among adults with and without probable, undiagnosed celiac disease (CD).Method: Cross-sectional data from What We Eat in America and the National Health and Nutrition Examination Survey 2009-2014 including self-reported dietary and supplement intake from one day of 24-hour recalls, serologic indicators, and dual x-ray absorptiometry scans were analyzed in adults with probable undiagnosed CD, who tested positive on the immunoglobulin A endomysial antibody assay (n = 48) and controls (n = 13,634). Statistical analysis included multiple linear regression modeling controlled for age, sex, race/ethnicity, energy intake, and poverty income ratio.Results: The prevalence of probable undiagnosed CD was 1 in 285. Probable CD status was associated with a 251.6 mg (95% confidence interval [CI], 72.3-432.9) higher daily total calcium intake. The total dietary and supplement intake of those with probable CD was significantly higher in calcium density (103.4 mg/1,000 kcal; 95% CI, 25.6-181.1) and phosphorus density (46.7 mg/1,000 kcal; 95% CI, 3.1-90.3). Probable CD status was associated with higher dairy consumption by 0.7 cups per day (95% CI, 0.2-1.2) and higher serum phosphorus concentrations (4.0 mg/dL vs 3.8 mg/dL, p = 0.011). No differences in serum calcium, vitamin D, or alkaline phosphatase levels were observed between groups. Probable CD status was also associated with a -0.1 g/cm2 (95% CI, -0.2 to -0.0) lower femur bone mineral density (BMD) and a -0.1 g/cm2 (95% CI, -0.1 to -0.0) lower femoral neck BMD. No differences in total spine BMD were observed.Conclusions: Adults with probable undiagnosed CD had lower bone density than adults without CD, despite also reporting higher total calcium intake and nutritional density of both calcium and phosphorus.

Multivitamin/Multimineral Supplement Use is Associated with Increased Micronutrient Intakes and Biomarkers and Decreased Prevalence of Inadequacies and Deficiencies in Middle-Aged and Older Adults in the United States.

Micronutrient inadequacies are common in older adults and using a multivitamin/multimineral supplement (MVM) may improve their nutritional status. National Health and Nutrition Examination Survey data were analyzed to determine micronutrient intakes based on diet and MVM use in adults aged ≥51 years. Deficiencies were evaluated using nutrient biomarkers. The National Cancer Institute Method was used to estimate usual intakes of 18 micronutrients stratified by age and frequency of MVM use. Compared with food alone, MVM use was associated with higher nutrient intake and lower prevalence of inadequacies of almost all micronutrients examined and improved nutrient biomarker status of folate, iodine, selenium, and vitamins B6, B12, and D. Regular MVM use (≥16 days/month) decreased the odds of clinical deficiency (defined by biomarker status) of vitamins B6 and D but increased the proportion exceeding the tolerable upper intake level of folic acid. Vitamin B6 deficiency in MVM non-users was common and increased with age.

rAAV-based brain slice culture models of Alzheimer's and Parkinson's disease inclusion pathologies.

It has been challenging to produce ex vivo models of the inclusion pathologies that are hallmark pathologies of many neurodegenerative diseases. Using three-dimensional mouse brain slice cultures (BSCs), we have developed a paradigm that rapidly and robustly recapitulates mature neurofibrillary inclusion and Lewy body formation found in Alzheimer's and Parkinson's disease, respectively. This was achieved by transducing the BSCs with recombinant adeno-associated viruses (rAAVs) that express α-synuclein or variants of tau. Notably, the tauopathy BSC model enables screening of small molecule therapeutics and tracking of neurodegeneration. More generally, the rAAV BSC "toolkit" enables efficient transduction and transgene expression from neurons, microglia, astrocytes, and oligodendrocytes, alone or in combination, with transgene expression lasting for many months. These rAAV-based BSC models provide a cost-effective and facile alternative to in vivo studies, and in the future can become a widely adopted methodology to explore physiological and pathological mechanisms related to brain function and dysfunction.

Apparent and true digestibility of macro and micro nutrients in adult maintenance dog foods containing either a majority of animal or vegetable proteins1.

There is dearth of knowledge with regards to mineral digestibility of ingredients in canines, and current knowledge is focused on the digestibility of supplemented minerals, not on intrinsic mineral digestibility of ingredients. The objectives of the present study were to determine the apparent and true digestibility (TD) of macronutrients and micronutrients, and the total tract gastrointestinal endogenous nutrient outputs in canines fed either animal- or vegetable-based adult maintenance diets. Eight purpose bred Beagles (two intact males, six spayed females) of similar age (2.12 ± 0.35 yr, mean ± SD) and weight (9.92 ± 0.73 kg, mean ± SD) were pair housed in kennels but fed individually based on individual maintenance energy requirements. Two basal diets (animal and vegetable protein based) were formulated to meet nutritional requirements of adult canines. Two additional trial diets were created, using the basal diets, by diluting diets by 50% with anhydrous α-d-glucose to attempt to quantify endogenous mineral losses and enable calculation of TD. All diets contained titanium dioxide at 0.3% for calculations of nutrient digestibility. Dogs were provided with deionized water as their only source of water throughout the trial. Dogs in a specific kennel were randomly assigned to an experimental diet for 10 d (experimental period), and fecal samples were collected the last 4 d of each period. All dogs were fed all experimental diets in random order based on a 4 × 4 replicated Latin square design. Dogs fed intact diets had a higher apparent mineral digestibility compared to dogs fed diluted diets (P < 0.05). Apparent phosphorus digestibility was higher for dogs fed the diet 2 compared with the diet 1 (P = 0.01) and the diluted diets (P < 0.001). There was a trend towards a greater TD of Cu for dogs fed the diet 2 compared with the diet 1 (P = 0.08). P, Mg, Zn, and Mn true digestibilities were higher for dogs fed the diet 2 compared with the diet 1 (P < 0.05, P = 0.01, P = 0.02, P = 0.009, respectively). These results suggest that apparent and TD do not result in similar values. Further research should be conducted on TD in canines only if a better model is developed.

Current Practices of Live Discharge from Hospice: Social Work Perspectives.

Hospice provides holistic support for individuals living with terminal illness and to their caregivers during the bereavement period. However, some individuals who enroll in hospice services are decertified as they do not experience a decline in health as quickly as required by current regulations, a practice referred to as a live discharge. The interruption in care can affect the physical and psychosocial care needs for individuals and caregivers and leave hospice clinicians with questions about how to best support them. However, there are no formal guidelines to support this process. This qualitative study (N = 24) explored the current practices of hospice social workers across the United States engaged in the live discharge process. Results from this study emphasize the need to bridge the gaps between policy and practice. Specifically, results highlight the challenges hospice social workers face to replicate or supplement the holistic support and unique services hospice provides for individuals discharged alive, and suggest further research to develop live discharge guidelines to identify appropriate support for patients and their caregivers who no longer meet hospice eligibility requirements.

Health, Social, and Functional Characteristics of Older Adults With Continuing Care Needs: Implications for Integrated Care.

Objective: To identify older adults who could benefit from integrated care, we examined (a) health, social, and functional characteristics of older, hospitalized adults who required continuing care on discharge and (b) associations between these characteristics and potentially unnecessary health care use. Method: Personal characteristics were extracted from patient charts (N = 214) and examined in relation to three outcomes: discharge to institutional care, unnecessary hospital stay (alternative level of care), and long hospital stay. Results: Twenty-nine percent of the sample was discharged to an institution, 32.7% was coded as alternate level of care, and 27.6% had a long length of stay. Independent predictors of potentially avoidable health care use were mental and behavioral issues, living alone, functional status, and preadmission concerns about the patient managing in the community. Discussion: High users of health care services were identifiable prior to hospital admission, supporting the use of community-based integrated care approaches.

Integrated Care Approaches Used for Transitions from Hospital to Community Care: A Scoping Review.

ABSTRACTIntegrated care is a promising approach for improving care transitions for older adults, but this concept is inconsistently defined and applied. This scoping review describes the size and nature of literature on integrated care initiatives for transitions from hospital to community care for older adults (aged 65 and older) and how this literature conceptualizes integrated care. A systematic search of literature from the past 10 years yielded 899 documents that were screened for inclusion by two reviewers. Of the 48 included documents, there were 26 journal articles and 22 grey literature documents. Analysis included descriptive statistics and a content analysis approach to summarize features of the integrated care initiatives. Results suggest that clinical and service delivery integration is being targeted rather than integration of funding, administration, and/or organization. To promote international comparison of integrated care initiatives aiming to improve care transitions, detailed descriptions of organizational context are also needed.

Examining the psychological and emotional mechanisms of mindfulness that reduce stress to enhance healthy behaviours.

Engagement in modifiable health behaviours plays a critical role in the development of chronic illnesses. Research suggests that mindfulness facilitates health-enhancing behaviour, yet the influence of mindfulness on different health behaviours and the mechanisms underlying this association are unclear. This study investigated a mediation model that explores psychological and emotional coping processes (reappraisal, suppression, and psychological flexibility) as mechanisms connecting mindfulness to reduced stress perceptions and reactions, which then predict physical activity, fruit and vegetable consumption, and sleep quality. Adults (n = 233) completed self-report measures via Amazon's Mechanical Turk and path modelling was used to test the model for direct, indirect, and total effects. Results revealed that greater mindfulness was indirectly associated with greater engagement in all 3 health behaviours through the proposed mediators, although the association with fruit and vegetable consumption was only trending in significance. Among the coping processes, psychological flexibility emerged as the strongest mechanism in the prediction of stress. Findings suggest that being more mindful may have downstream stress-reductive effects that enhance engagement in healthy behaviour, supporting mindfulness as a potential addition to behavioural health interventions.

End-of-Life Care in Nursing Homes: A Qualitative Interpretive Meta-Synthesis.

BACKGROUND: Due to large number of deaths occurring in nursing home (NH) settings, along with reports of pain and suffering, there is great need for improvements in the provision of end-of-life (EOL) care in NHs. OBJECTIVE: The aim of this study was to develop a comprehensive understanding of the experience of dying in NHs through the perspective of residents, family, and facility staff. DESIGN: This study uses a qualitative interpretive meta-synthesis to provide a holistic view of EOL care in NHs across multiple qualitative studies. SETTING/SUBJECTS: Researchers synthesized the findings of 13 qualitative articles, including the diverse perspective of 91 dying residents, 419 NH staff, and 156 family members/caregivers across at least 44 NHs. METHODS: A qualitative meta-synthesis employs the following steps: identification of studies, theme extraction, translation, and synthesis of findings. RESULTS: Thematic analysis is organized using a conceptual model demonstrating the links between environmental and personal factors impacting EOL care in NHs. CONCLUSIONS: Findings provide support for the importance of a relational community and culture change within NHs for positive EOL experiences, in addition to providing a model to guide future research priorities.

Inhibition of glycogen synthase kinase-3 by BTA-EG4 reduces tau abnormalities in an organotypic brain slice culture model of Alzheimer's disease.

Organotypic brain slice culture models provide an alternative to early stage in vivo studies as an integrated tissue system that can recapitulate key disease features, thereby providing an excellent platform for drug screening. We recently described a novel organotypic 3xTg-AD mouse brain slice culture model with key Alzheimer's disease-like changes. We now highlight the potential of this model for testing disease-modifying agents and show that results obtained following in vivo treatment are replicated in brain slice cultures from 3xTg-AD mice. Moreover, we describe novel effects of the amyloid-binding tetra (ethylene glycol) derivative of benzothiazole aniline, BTA-EG4, on tau. BTA-EG4 significantly reduced tau phosphorylation in the absence of any changes in the amounts of amyloid precursor protein, amyloid-ß or synaptic proteins. The reduction in tau phosphorylation was associated with inactivation of the Alzheimer's disease-relevant major tau kinase, GSK-3. These findings highlight the utility of 3xTg-AD brain slice cultures as a rapid and reliable in vitro method for drug screening prior to in vivo testing. Furthermore, we demonstrate novel tau-directed effects of BTA-EG4 that are likely related to the ability of this agent to inactivate GSK-3. Our findings support the further exploration of BTA-EG4 as a candidate therapeutic for Alzheimer's disease.

IAGG/IAGG GARN International Survey of End-of-Life Care in Nursing Homes.

This article reports the findings of a survey on end-of-life (EOL) care in nursing homes of 18 long-term care experts across 15 countries. The experts were chosen as a convenience-based sample of known experts in each country. The survey was administered in 2016 and included both open-ended responses for defining hospice care, palliative care, and "end of life," and a series of questions related to the following areas-attitudes toward EOL care, current practice and EOL interventions, structure of care, and routine barriers. Overall experts strongly agreed that hospice and palliative care should be available in long-term care facilities and that both are defined by holistic, interdisciplinary approaches using measures of comfort across domains. However, it appears the experts felt that in most countries the reality fell short of what they believed would be ideal care. As a result, experts call for increased training, communication, and access to specialized EOL services within the nursing home.

Examining hospice enrollment through a novel lens: Decision time.

OBJECTIVE: No prior studies on hospice utilization have captured information about the amount of time between when one first learns of hospice as a potential option for care and when he/she actually enrolls. Little is in fact known about this decision-making process. The present study examines hospice enrollment by exploring relationships between hospice decision time and known barriers to care. METHOD: This was an exploratory cross-sectional study. Pearson's r was employed to identify bivariate relationships between barriers to care and decision time for hospice care. Independent-sample t tests and ANOVA were utilized to consider differences in decision time across key variables. RESULTS: Some 90 hospice patients, or their primary decision maker, participated in the study from a not-for-profit hospice located in the southern United States. Decision time was correlated with referral source, use of disease-directed treatment, functional status (on the Palliative Performance Scale [PPS]), age, diagnosis, income, race, and spirituality-suggesting that decision time is a pertinent variable when examining hospice utilization. Differences in decision time were found across diagnosis, race, income, and referral source. SIGNIFICANCE OF RESULTS: This study provides implications for policy and practice, particularly for clinicians faced with initial conversations about hospice care. Differences in decision time highlight ongoing needs related to overcoming healthcare disparities, the important role of including families in initial conversations, and the potential need for varied approaches to talking about hospice care based upon diagnosis. Results also highlight the need for policies supportive of concurrent care, where hospice can be accessed alongside curative care.