Involvement of the gut microbiota in cancer cachexia.

Cancer cachexia, or the unintentional loss of body weight in cancer patients, is a multi-organ and multi-factorial syndrome with a complex and largely unknown etiology; however, metabolic dysfunction and inflammation remain hallmarks of cancer-associated wasting. While cachexia manifests with muscle and adipose tissue loss, perturbations to the gastrointestinal tract may serve as the front line for both impaired nutrient absorption and immune activating gut dysbiosis. Investigations into the gut microbiota have exploded within the past 2 decades, demonstrating multiple gut-tissue axes; however, the link between adipose and skeletal muscle wasting and the gut microbiota with cancer is only beginning to be understood. Further, the most used anti-cancer drugs (e.g. chemotherapy, immune checkpoint inhibitors) negatively impact gut homeostasis, potentially exacerbating wasting and contributing to poor patient outcomes and survival. In this current review, we 1) highlight our current understanding of the microbial changes that occur with cachexia, 2) discuss how microbial changes may contribute to adipose and skeletal muscle wasting, and 3) outline study design considerations needed when examining the role of the microbiota in cancer-induced cachexia.

Decreased skeletal muscle intramyocellular lipid droplet-mitochondrial contact contributes to myosteatosis in cancer cachexia.

Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. While its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular LD content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis Lung Carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n=20) were implanted with LLC cells [106] in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red o/lipid staining (tibialis anterior), and protein (gastrocnemius). LLC mice had a greater number (232%; p=0.006) and size (130%; p=0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; p=0.0109) and 'very high' oil-red O positive (178%; p=0.0002) fibers compared to controls and this was inversely correlated with fiber size (R2=0.5294; p<0.0001). Morphological analyses of LDs show increased elongation and complexity (aspect ratio: IMF: 9%, p=0.046) with decreases in circularity (circularity: SS: 6%, p=0.042) or roundness (roundness: Whole: 10%, p=0.033; IMF: 8%, p=0.038) as well as decreased LD-mitochondria touch (-15%; p=0.006), contact length (-38%; p=0.036), and relative contact (86%; p=0.004). Further, dysregulation in lipid metabolism (adiponectin, CPT-1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (p<0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia.

Panaxynol improves crypt and mucosal architecture, suppresses colitis-enriched microbes, and alters the immune response to mitigate colitis.

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.

Potential of Plant-Derived Compounds in Preventing and Reversing Organ Fibrosis and the Underlying Mechanisms.

Increased production of extracellular matrix is a necessary response to tissue damage and stress. In a normal healing process, the increase in extracellular matrix is transient. In some instances; however, the increase in extracellular matrix can persist as fibrosis, leading to deleterious alterations in organ structure, biomechanical properties, and function. Indeed, fibrosis is now appreciated to be an important cause of mortality and morbidity. Extensive research has illustrated that fibrosis can be slowed, arrested or even reversed; however, few drugs have been approved specifically for anti-fibrotic treatment. This is in part due to the complex pathways responsible for fibrogenesis and the undesirable side effects of drugs targeting these pathways. Natural products have been utilized for thousands of years as a major component of traditional medicine and currently account for almost one-third of drugs used clinically worldwide. A variety of plant-derived compounds have been demonstrated to have preventative or even reversal effects on fibrosis. This review will discuss the effects and the underlying mechanisms of some of the major plant-derived compounds that have been identified to impact fibrosis.

The complex heterogeneity of immune cell signatures across wasting tissues with C26 and 5-fluorouracil-induced cachexia.

Immune cell-driven pathways are linked to cancer cachexia. Tumor presence is associated with immune cell infiltration whereas cytotoxic chemotherapies reduce immune cell counts. Despite these paradoxical effects, both cancer and chemotherapy can cause cachexia; however, our understanding of immune responses in the cachexia condition with cancer and chemotherapy is largely unknown. We sought to advance our understanding of the immunology underlying cancer and cancer with chemotherapy-induced cachexia. CD2F1 mice were given 106 C26 cells, followed by five doses of 5-fluorouracil (5FU; 30 mg/kg LM, ip) or PBS. Indices of cachexia and tumor (TUM), skeletal muscle (SKM), and adipose tissue (AT) immune cell populations were examined using high-parameter flow cytometry. Although 5FU was able to stunt tumor growth, % body weight loss and muscle mass were not different between C26 and C26 + 5FU. C26 increased CD11b+Ly6g+ and CD11b+Ly6cInt inflammatory myeloid cells in SKM and AT; however, both populations were reduced with C26 + 5FU. tSNE analysis revealed 24 SKM macrophage subsets wherein 8 were changed with C26 or C26 + 5FU. C26 + 5FU increased SKM CD11b-CD11c+ dendritic cells, CD11b-NK1.1+ NK-cells, and CD11b-B220+ B-cells, and reduced Ly6cHiCX3CR1+CD206+CD163IntCD11c-MHCII- infiltrated macrophages and other CD11b+Ly6cHi myeloid cells compared with C26. Both C26 and C26 + 5FU had elevated CD11b+F480+CD206+MHCII- or more specifically Ly6cLoCX3CR1+CD206+CD163IntCD11c-MHCII- profibrotic macrophages. 5FU suppressed tumor growth and decreased SKM and AT inflammatory immune cells without protecting against cachexia suggesting that these cells are not required for wasting. However, profibrotic cells and muscle inflammatory/atrophic signaling appear consistent with cancer- and cancer with chemotherapy-induced wasting and remain potential therapeutic targets.NEW & NOTEWORTHY Despite being an immune-driven condition, our understanding of skeletal muscle and adipose tissue immune cells with cachexia is limited. Here, we identified immune cell populations in tumors, skeletal muscle, and adipose tissue in C26 tumor-bearing mice with/without 5-fluorouracil (5FU). C26 and C26 + 5FU had increased skeletal muscle profibrotic macrophages, but 5FU reduced inflammatory myeloid cells without sparing mass. Tumor presence and chemotherapy have contrasting effects on certain immune cells, which appeared not necessary for wasting.

Improved adherence to hip fracture standards reduces mortality after hip fractures.

BACKGROUND: Hip fractures are increasing in incidence due to increasing life expectancy. Mortality continues to improve but it is important to explore which factors are responsible for driving improvements. METHODS: A cohort of hip fracture patients predating SARS-CoV-2 was examined to determine the predictors of adherence to the six Irish Hip Fracture Standards (IHFS) and the impact of adherence on short (30 day) and long term (1 year) mortality. Our primary aim was assess the impact of a single HFS and cumulative number of HFS on mortality after hip fracture. Our secondary aim was to determine the impact of the HFS which are intrinsically linked to specialist Geriatric care. RESULTS: Across 962 patients, over 5 years, the factors which were associated with adherence to HFS were female gender, increasing ASA grade and being nursed on an orthopaedic ward. Patients with increasing ASA were more likely to have met HFS 4-6 (Geriatrician review HFS4, bone health HFS5 & specialist falls assessment HFS6), less likely to have surgery within 48 h are more likely to develop a pressure ulcer. If the patient was not nursed on an orthopaedic ward all HFS were less likely to be met. At 30 days HFS 4-6 were associated with a statistically significant odds ratio (OR) of being alive, while at one year HFS 1 (admitted to an orthopaedic ward within 4 h), 5 and 6 were associated with a statistically significant OR of being alive. As increasing numbers of hip fracture standards were met patients were more likely to be alive at 30 days and one year. CONCLUSION: This study has identified that improved adherence to hip fracture standards are associated with improved mortality at 30 days and one year.

Obesity worsens mitochondrial quality control and does not protect against skeletal muscle wasting in murine cancer cachexia.

BACKGROUND: More than 650 million people are obese (BMI > 30) worldwide, which increases their risk for several metabolic diseases and cancer. While cachexia and obesity are at opposite ends of the weight spectrum, leading many to suggest a protective effect of obesity against cachexia, mechanistic support for obesity's benefit is lacking. Given that obesity and cachexia are both accompanied by metabolic dysregulation, we sought to investigate the impact of obesity on skeletal muscle mass loss and mitochondrial dysfunction in murine cancer cachexia. METHODS: Male C57BL/6 mice were given a purified high fat or standard diet for 16 weeks before being implanted with 106 Lewis lung carcinoma (LLC) cells. Mice were monitored for 25 days, and hindlimb muscles were collected for cachexia indices and mitochondrial assessment via western blotting, high-resolution respirometry and transmission electron microscopy (TEM). RESULTS: Obese LLC mice experienced significant tumour-free body weight loss similar to lean (-12.8% vs. -11.8%, P = 0.0001) but had reduced survival (33.3% vs. 6.67%, χ2  = 10.04, P = 0.0182). Obese LLC mice had reduced muscle weights (-24%, P < 0.0354) and mCSA (-16%, P = 0.0004) with similar activation of muscle p65 (P = 0.0337), and p38 (P = 0.0008). ADP-dependent coupled respiration was reduced in both Obese and Obese LLC muscle (-30%, P = 0.0072) consistent with reductions in volitional cage activity (-39%, P < 0.0001) and grip strength (-41%, P < 0.0001). TEM revealed stepwise reductions in intermyofibrillar and subsarcolemmal mitochondrial size with Obese (IMF: -37%, P = 0.0009; SS: -21%, P = 0.0101) and LLC (IMF: -40%, P = 0.0019; SS: -27%, P = 0.0383) mice. Obese LLC mice had increased pAMPK (T172; P = 0.0103) and reduced FIS1 (P = 0.0029) and DRP1 (P < 0.0001) mitochondrial fission proteins, which were each unchanged in Lean LLC. Further, mitochondrial TEM analysis revealed that Obese LLC mice had an accumulation of damaged and dysfunctional mitochondria (IMF: 357%, P = 0.0395; SS: 138%, P = 0.0174) in concert with an accumulation of p62 (P = 0.0328) suggesting impaired autophagy and clearance of damaged mitochondria. Moreover, we observed increases in electron lucent vacuoles only in Obese LLC muscle (IMF: 421%, P = 0.0260; SS: 392%, P = 0.0192), further supporting an accumulation of damaged materials that cannot be properly cleared in the obese cachectic muscle. CONCLUSIONS: Taken together, these results demonstrate that obesity is not protective against cachexia and suggest exacerbated impairments to mitochondrial function and quality control with a particular disruption in the removal of damaged mitochondria. Our findings highlight the need for consideration of the severity of obesity and pre-existing metabolic conditions when determining the impact of weight status on cancer-induced cachexia and functional mitochondrial deficits.

Emodin reduces surgical wounding-accelerated tumor growth and metastasis via macrophage suppression in a murine triple-negative breast cancer model.

It has been suspected that tumor resection surgery itself may accelerate breast cancer (BC) lung metastasis in some patients. Emodin, a natural anthraquinone found in the roots and rhizomes of various plants, exhibits anticancer activity. We examined the perioperative use of emodin in our established surgery wounding murine BC model. Emodin reduced primary BC tumor growth and metastasis in the lungs in both sham and surgical wounded mice, consistent with a reduction in proliferation and enhanced apoptosis (primary tumor and lungs). Further, emodin reduced systemic inflammation, most notably the number of monocytes in the peripheral blood and reduced pro-tumoral M2 macrophages in the primary tumor and the lungs. Consistently, we show that emodin reduces gene expression of select macrophage markers and associated cytokines in the primary tumor and lungs of wounded mice. Overall, we demonstrate that emodin is beneficial in mitigating surgical wounding accelerated lung metastasis in a model of triple-negative BC, which appears to be mediated, at least in part, by its actions on macrophages. These data support the development of emodin as a safe, low-cost, and effective agent to be used perioperatively to alleviate the surgery triggered inflammatory response and consequential metastasis of BC to the lungs.

Neurodevelopmental outcomes in children and adults with Fetal Valproate Spectrum Disorder: A contribution from the ConcePTION project.

AIM: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD). METHODS: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day. RESULTS: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services. INTERPRETATION: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

Platelet status in cancer cachexia progression in ApcMin/+ mice.

Cachexia, a complex wasting syndrome, significantly affects the quality of life and treatment options for cancer patients. Studies have reported a strong correlation between high platelet count and decreased survival in cachectic individuals. Therefore, this study aimed to investigate the immunopathogenesis of cancer cachexia using the ApcMin/+ mouse model of spontaneous colorectal cancer. The research focused on identifying cellular elements in the blood at different stages of cancer cachexia, assessing inflammatory markers and fibrogenic factors in the skeletal muscle, and studying the behavioral and metabolic phenotype of ApcMin/+ mice at the pre-cachectic and severely cachectic stages. Platelet measurements were also obtained from other animal models of cancer cachexia - Lewis Lung Carcinoma and Colon 26 adenocarcinoma. Our study revealed that platelet number is elevated prior to cachexia development in ApcMin/+ mice and can become activated during its progression. We also observed increased expression of TGFß2, TGFß3, and SMAD3 in the skeletal muscle of pre-cachectic ApcMin/+ mice. In severely cachectic mice, we observed an increase in Ly6g, CD206, and IL-10 mRNA. Meanwhile, IL-1ß gene expression was elevated in the pre-cachectic stage. Our behavioral and metabolic phenotyping results indicate that pre-cachectic ApcMin/+ mice exhibit decreased physical activity. Additionally, we found an increase in anemia at pre-cachectic and severely cachectic stages. These findings highlight the altered platelet status during early and late stages of cachexia and provide a basis for further investigation of platelets in the field of cancer cachexia.

Genetic counseling graduate program faculty perspectives on sharing education materials among programs.

Rapid advancements in genetics care requires responsive genetic counseling (GC) training capable of integrating new discoveries and practice into their curricula. The utilization of shared or standardized educational resources may address this need. Recognizing the potential of shared resources, the Pharmacogenetics (PGx) Working Group of the NSGC Precision Medicine Special Interest Group (SIG) launched a standardized education module using a flipped-classroom format to provide all GC programs equal access to PGx expertise and alleviate the burden of curriculum development. Following the initial success of the program, we aimed to explore the utilization of shared and standardized education resources more broadly, and better understand the perspectives of GC program faculty regarding their use. Twenty-nine program faculty representing at least 14 programs responded to an online survey. The majority (n = 21) reported sharing educational materials with another GC program, and 90% of those reported the shared materials to be beneficial as they promote collaboration, efficiency, address a gap in content, and provide access to experts. Similar benefits were described when using a standardized curriculum, which was defined as standardized lectures and activities created about a particular topic and made available to all genetic counseling programs; 16 participants indicated they would be very likely or likely to use a standardized curriculum. A secondary aim of the survey was to assess the existing PGx module that utilizes a flipped-classroom format. Overall, the PGx module was well received, indicating that a standardized shared module is well-suited for instruction on emerging and specialty topics. All participants believed the flipped-classroom format to be very or somewhat beneficial. In summary, results indicate that shared educational materials, including standardized education modules, are a potential solution to challenges related to efficiency and access to content experts in GC education, and program leadership is receptive to using them.

The synthetic food dye, Red 40, causes DNA damage, causes colonic inflammation, and impacts the microbiome in mice.

The incidence of colorectal cancer (CRC) among young people has been on the rise for the past four decades and its underlying causes are only just starting to be uncovered. Recent studies suggest that consuming ultra-processed foods and pro-inflammatory diets may be contributing factors. The increase in the use of synthetic food colors in such foods over the past 40 years, including the common synthetic food dye Allura Red AC (Red 40), coincides with the rise of early-onset colorectal cancer (EOCRC). As these ultra-processed foods are particularly appealing to children, there is a growing concern about the impact of synthetic food dyes on the development of CRC. Our study aimed to investigate the effects of Red 40 on DNA damage, the microbiome, and colonic inflammation. Despite a lack of prior research, high levels of human exposure to pro-inflammatory foods containing Red 40 highlight the urgency of exploring this issue. Our results show that Red 40 damages DNA both in vitro and in vivo and that consumption of Red 40 in the presence of a high-fat diet for 10 months leads to dysbiosis and low-grade colonic inflammation in mice. This evidence supports the hypothesis that Red 40 is a dangerous compound that dysregulates key players involved in the development of EOCRC.

Panaxynol alleviates colorectal cancer in a murine model via suppressing macrophages and inflammation.

Currently available colorectal cancer (CRC) therapies have limited efficacy and severe adverse effects that may be overcome with the alternative use of natural compounds. We previously reported that panaxynol (PA), a bioactive component in American ginseng, possesses anticancer properties in vitro and suppresses murine colitis through its proapoptotic and anti-inflammatory properties. Because colitis is a predisposing factor of CRC and inflammation is a major driver of CRC, we sought to evaluate the therapeutic potential of PA in CRC. Azoxymethane-dextran sodium sulfate (AOM/DSS) mice (C57BL/6) were administered 2.5 mg/kg PA or vehicle 3 times/wk via oral gavage over 12 wk. PA improved clinical symptoms (P ≤ 0.05) and reduced tumorigenesis (P ≤ 0.05). This improvement may be reflective of PA's restorative effect on intestinal barrier function; PA upregulated the expression of essential tight junction and mucin genes (P ≤ 0.05) and increased the abundance of mucin-producing goblet cells (P ≤ 0.05). Given that macrophages play a substantial role in the pathogenesis of CRC and that we previously demonstrated that PA targets macrophages in colitis, we next assessed macrophages. We show that PA reduces the relative abundance of colonic macrophages within the lamina propria (P ≤ 0.05), and this was consistent with a reduction in the expression of important markers of macrophages and inflammation (P ≤ 0.05). We further confirmed PA's inhibitory effects on macrophages in vitro under CRC conditions (P ≤ 0.05). These results suggest that PA is a promising therapeutic compound to treat CRC and improve clinical symptoms given its ability to inhibit macrophages and modulate the inflammatory environment in the colon.NEW & NOTEWORTHY We report that panaxynol (PA) reduces colorectal cancer (CRC) by improving the colonic and tumor environment. Specifically, we demonstrate that PA improves crypt morphology, upregulates crucial tight junction and mucin genes, and promotes the abundance of mucin-producing goblet cells. Furthermore, PA reduces macrophages and associated inflammation, important drivers of CRC, in the colonic environment. This present study provides novel insights into the potential of PA as a therapeutic agent to ameliorate CRC tumorigenesis.

Optimizing patient outcomes: Health plans and pharmacists summit: Meeting proceedings.

OBJECTIVE: To convene a group of experts to define the value pharmacists provide to health plans, barriers to covering pharmacists' patient care services, and scalable solutions to cover pharmacists' services, specifically in the medical benefit. METHODS: The American Pharmacists Association (APhA) convened 31 experts, including physicians and pharmacists representing health plans (HPs), and pharmacist practitioners (PP) or organizations representing PPs for a strategic summit on May 16 to May 17, 2022, in Washington DC and Arlington, VA. A presummit survey was conducted to identify participants' perspectives on the value proposition of pharmacists and barriers to coverage for services. Day 1 of the summit featured a keynote presentation focused on the future of pharmacist-provided care. The second day included a framing session on the current state of coverage for pharmacists' services and the results of the presummit survey; four panel presentations on innovative HP program coverage; three breakout sessions to gather participant feedback on their experiences; and a final session prioritizing action items into an initial timeline of goals. A postsummit survey was fielded to rank feasibility and importance of opportunities and next steps for advancing coverage of pharmacists' services. RESULT: In general, there appeared to be consensus throughout the summit on the need to expand payer programs covering patient care services provided by pharmacists and the importance of continued collaboration between PPs and HPs to increase patient access to care. Participants highlighted a need for legislative and regulatory changes at the state and federal level for the expansion of some programs; however, there were many opportunities to expand programs without the need for public policy changes. CONCLUSION: The summit was a groundbreaking meeting between PPs and HPs that provided the foundation for collaboration and expansion of programs covering pharmacists' patient care services under the medical benefit. Key takeaways from the summit focused on the need for scaling programs; establishing mutually beneficial programs for patients, PPs, and HPs; and the need for partnership and flexibility from PPs and HPs as programs continue to establish and expand.

Nursing, midwifery, and allied health professions research capacities and cultures: a survey of staff within a university and acute healthcare organisation.

BACKGROUND: There is an increasing focus on the development of research capacity and culture in Nursing, Midwifery and Allied Health Professions (NMAHP). However, better understanding of the existing research success and skills, motivators, barriers, and development needs of NMAHP professionals is required to inform this development. This study sought to identify such factors within a university and an acute healthcare organisation. METHODS: An online survey, incorporating the Research Capacity and Culture tool, was administered to NMAHP professionals and students at a university and an acute healthcare organisation in the United Kingdom. Ratings of success/skill levels of teams and individuals were compared between professional groups using Mann-Whitney U tests. Motivators, barriers, and development needs were reported using descriptive statistics. Descriptive thematic analysis was used for open-ended text responses. RESULTS: A total of 416 responses were received (N&M n = 223, AHP n = 133, Other n = 60). N&M respondents were more positive than their AHP counterparts about the success/skill levels of their teams. There were no significant differences between N&M and AHP in their ratings of individual successes/skills. Finding and critically reviewing relevant literature were identified as specific individual strengths; with weaknesses in securing research funding, submitting ethics applications, writing for publication, and advising less experienced researchers. The main motivators for research were to develop skills, increased job satisfaction, and career advancement; whilst barriers included lack of time for research and other work roles taking priority. Key support needs identified included mentorship (for teams and individuals) and in-service training. Open-ended questions generated main themes of 'Employment & staffing', 'Professional services support', 'Clinical & academic management', 'Training & development', 'Partnerships' and 'Operating principles'. Two cross-cutting themes described issues common to multiple main themes: 'Adequate working time for research' and 'Participating in research as an individual learning journey'. CONCLUSIONS: Rich information was generated to inform the development of strategies to enhance research capacity and culture in NMAHP. Much of this can be generic but some nuances may be required to address some specific differences between professional groups, particularly related to perceived team success/skills and priorities identified for support and development.

Ischaemic stroke with multi-focal venous and arterial thrombosis due to hyperhomocysteinemia: anabolic androgenic steroid use and MTHFR c.667 C > T variant - a case report.

BACKGROUND: Severely elevated serum homocysteine is a rare cause of ischaemic stroke and extra-cranial arterial and venous thrombosis. Several factors can lead to mild elevation of homocysteine including dietary folate and B12 deficiency, and genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The use of Anabolic androgenic steroid (AAS) is under-reported, but increasingly linked to ischaemic stroke and can raise homocysteine levels. CASE REPORT: We present a case of a man in his 40s with a large left middle cerebral artery (MCA) territory ischaemic stroke and combined multifocal, extracranial venous, and arterial thrombosis. His past medical history was significant for Crohn's disease and covert use of AAS. A young stroke screen was negative except for a severely elevated total homocysteine concentration, folate and B12 deficiencies. Further tests revealed he was homozygous for the methylenetetrahydrofolate reductase enzyme thermolabile variant (MTHFR c.667 C > T). The etiology of this stroke was a hypercoagulable state induced by raised plasma homocysteine. Raised homocysteine in this case was likely multifactorial and related to chronic AAS use in combination with the homozygous MTHFR c.677 C > T thermolabile variant, folate deficiency and, vitamin B12 deficiency. CONCLUSION: In summary, hyperhomocysteinemia is an important potential cause of ischaemic stroke and may result from genetic, dietary, and social factors. Anabolic androgenic steroid use is an important risk factor for clinicians to consider, particularly in cases of young stroke with elevated serum homocysteine. Testing for MFTHR variants in stroke patients with raised homocysteine may be useful to guide secondary stroke prevention through adequate vitamin supplementation. Further studies looking into primary and secondary stroke prevention in the high-risk MTHFR variant cohort are necessary.

Prevalence of health behaviors among cancer survivors in the United States.

PURPOSE: We determined the proportion of cancer survivors who met each of five health behavior guidelines recommended by the American Cancer Society (ACS), including consuming fruits and vegetables at least five times/day, maintaining a body mass index (BMI) < 30 kg/m2, engaging in 150 min or more of physical activity weekly, not currently smoking, and not excessively drinking alcohol. METHODS: Using data from the 2019 Behavioral Risk Factor Surveillance System (BRFSS), 42,727 survey respondents who reported a previous diagnosis of cancer (excluding skin cancer) were included. Weighted percentages with 95% confidence intervals (95% CI) were estimated for the five health behaviors accounting for BRFSS' complex survey design. RESULTS: The weighted percentage of cancer survivors who met ACS guidelines was 15.1% (95%CI: 14.3%, 15.9%) for fruit and vegetable intake; 66.8% (95%CI: 65.9%, 67.7%) for BMI < 30 kg/m2; 51.1% (95%CI: 50.1%, 52.1%) for physical activity; 84.9% (95%CI: 84.1%, 85.7%) for not currently smoking; and 89.5% (95%CI: 88.8%, 90.3%) for not drinking excessive alcohol. Adherence to ACS guidelines among cancer survivors generally increased with increasing age, income, and education. CONCLUSIONS: While the majority of cancer survivors met the guidelines for not smoking and limiting alcohol drinking, one-third had elevated BMI, almost half did not meet recommended physical activity levels, and the majority had inadequate fruit and vegetable intake. IMPLICATIONS FOR CANCER SURVIVORS: Adherence to guidelines was lowest among younger cancer survivors and those with lower income and education, suggesting these may be populations where resources could be targeted to have the greatest impact.

Effect of a Plant-Based vs Omnivorous Soul Food Diet on Weight and Lipid Levels Among African American Adults: A Randomized Clinical Trial.

Importance: More African American individuals die from cardiovascular disease (CVD) than any other chronic disease condition. Despite this disparity, African American individuals are underrepresented in nutrition and CVD interventions. Objective: To compare the effects of an entirely plant-based (vegan) or low-fat omnivorous (omni) diet on change in body weight and lipids during a 2-year intervention. Design, Setting, and Participants: The Nutritious Eating With Soul (NEW Soul) study was a 2-year, randomized clinical trial conducted in 2 cohorts (2018-2020 and 2019-2021) that took place in a university teaching kitchen in Columbia, South Carolina (before March 2020), and via online videoconference sessions (after March 2020). Participants included African American adults aged 18 to 65 years with overweight or obesity (body mass index of 25.0-49.9) and without type 2 diabetes, uncontrolled thyroid disease, recent weight loss, or pregnancy. Data assessors and statisticians were blinded to study condition. Data analysis was performed from March to June 2022. Interventions: The intervention included weekly nutrition classes for 6 months biweekly classes for 6 months, and monthly classes for 12 months. Dietary interventions either emphasized no animal product intake (vegan) or a low-fat omnivorous diet (omni). Both dietary patterns emphasized soul food cuisine (traditional African American southern foodways). Main Outcomes and Measures: Primary outcomes included change in body weight and lipid measures at 12 months. Results: There were 568 participants who completed an online screening questionnaire; 409 were excluded and 159 were randomized (77 to the vegan group and 82 to the omni group). Of the 159 participants (mean [SD] age, 48.4 [10.6] years; 126 female [79%]) who began the study, the main outcome of body weight was obtained for 121 participants (76%) at 12 months. There were no differences in outcomes between groups, including 12-month changes in weight (mean, -2.39 kg [95% CI, -3.48 to -1.30 kg] for the vegan group vs -2.03 kg [95% CI, -3.07 to -1.00 kg] for the omni group; P = .64), total cholesterol (-1.05 mg/dL [95% CI, -9.60 to 7.50 mg/dL] for the vegan group vs 1.66 mg/dL [95% CI, -7.20 to 10.50 mg/dL] for the omni group; P = .67), or low-density lipoprotein cholesterol (mean, -2.56 mg/dL [95% CI, -9.52 to 4.40 mg/dL] for the vegan group vs -0.79 mg/dL [95% CI, -7.98 to 6.40 mg/dL] for the omni group; P = .73). Weight loss at 12 months among cohort 1, whose weight was assessed in 2019 before the COVID-19 pandemic, was significantly greater than that for cohort 2, whose weight was assessed summer 2020 during COVID-19 (-3.45 kg [95% CI, -4.67 to -2.22 kg] vs -1.24 kg [95% CI, -2.24 to -0.25 kg]; P = .01). Conclusions and Relevance: In this randomized clinical trial examining weight loss and CVD risk factor reduction among African American adults, there were no differences between the groups, and the magnitude of changes overall was small. Trial Registration: ClinicalTrials.gov Identifier: NCT03354377.

Determining and regulating scope of practice for health care professionals: A participatory, multiple stakeholder approach.

BACKGROUND: Scope of practice varies between health professions and states. OBJECTIVE: To explore stakeholders' preferences for determining and regulating health care professionals' scopes of practice. METHODS: Stakeholders in medicine, nursing, and pharmacy, including practitioners, leaders of professional associations, regulatory board members, and healthcare executives, were recruited via professional organizations, social media, and snowball sampling. Stakeholder preferences were collected using concept mapping, an integrated mixed methods approach which includes 1) brainstorming of statements and 2) sorting and rating of statements. Multidimensional scaling, hierarchical cluster analysis, and Mann Whitney-U tests were used for analysis. RESULTS: Thirty participants generated and sorted statements regarding preferences for scope of practice, creating eight clusters: 1) accountability to prioritize patient safety, 2) standardization, 3) collaborative regulation, 4) intra-professional regulation, 5) federal versus state, 6) role of non-health care professionals, 7) prioritization of patient outcomes, and 8) health care professional training and education. Fifty-seven participants rated statements in terms of importance and feasibility. Physicians and non-physicians held similar views on 68.5% (n = 37) and 81.5% (n = 44) of statements, respectively for importance and feasibility. The statements in the standardization and health care professional training and education clusters were perceived as the most important and feasible across stakeholder types.