Predictors of COVID-19 infection and hospitalization in group homes for individuals with intellectual and/or developmental disabilities.

BACKGROUND: More than seven million people with intellectual and/or developmental disabilities (ID/DD) live in the US and may face an elevated risk for COVID-19. OBJECTIVE: To identify correlates of COVID-19 and related hospitalizations among people with ID/DD in group homes in Massachusetts. METHODS: We collected data during March 1, 2020-June 30, 2020 (wave 1) and July 1, 2020-March 31, 2021 (wave 2) from the Massachusetts Department of Public Health and six organizations administering 206 group homes for 1035 residents with ID/DD. The main outcomes were COVID-19 infections and related hospitalizations. We fit multilevel Cox proportional hazards models to estimate associations with observed predictors and assess contextual home- and organizational-level effects. RESULTS: Compared with Massachusetts residents, group home residents had a higher age-adjusted rate of COVID-19 in wave 1 (incidence rate ratio [IRR], 12.06; 95 % confidence interval [CI], 10.51-13.84) and wave 2 (IRR, 2.47; 95 % CI, 2.12-2.88) and a higher age-adjusted rate of COVID-19 hospitalizations in wave 1 (IRR, 17.64; 95 % CI, 12.59-24.70) and wave 2 (IRR, 4.95; 95 % CI, 3.23-7.60). COVID-19 infections and hospitalizations were more likely among residents aged 65+ and in group homes with 6+ resident beds and recent infection among staff and residents. CONCLUSIONS: Aggressive efforts to decrease resident density, staff-to-resident ratios, and staff infections through efforts such as vaccination, in addition to ongoing access to personal protective equipment and COVID-19 testing, may reduce COVID-19 and related hospitalizations in people with ID/DD living in group homes.

Implementation outcomes of a digital, trauma-informed care, educational intervention targeting health professionals in a paediatric burns setting: A mixed methods process evaluation.

Trauma-informed care practices are associated with a culture of safety following traumatic experiences, including medical trauma. An interactive, web-based training package ('Responsive CARE') was developed for voluntary uptake by paediatric burns health professionals to increase staff knowledge about trauma-informed practice. This paper reports on a mixed methods process evaluation conducted alongside a preliminary effectiveness study of 'Responsive CARE'. The process evaluation was conducted using The Consolidated Framework for Implementation Research (CFIR) and a logic model, to examine feasibility of both the intervention and implementation strategy. Health practitioners (including senior managers) delivering care to children and caregivers attending an outpatient burns service were eligible to enrol in 'Responsive CARE'. Qualitative interview data and quantitative metadata were used to evaluate the implementation outcomes (adoption, acceptability, fidelity, feasibility and preliminary effectiveness). Children and caregivers attending an outpatient service for change of burn wound dressing or burn scar management during the 3-month control or 3-month intervention period were eligible to enrol in the effectiveness study. The impact on child pain and distress, as well as cost, was investigated using a pretest-posttest design. Thirteen (from anticipated 50 enrolled) health professionals (all female) with mean 10 years (SD=11) of experience with paediatric burns hospital-based outpatient care completed an average of 65% (range 36% to 88%) of available content. Twenty-five semi-structured interviews were completed with health practitioners (21 female) and with 14 caregivers (11 female). Four themes were identified as influencing feasibility and acceptability of the intervention: 1) Keeping a trauma-informed lens; 2) Ways of incorporating trauma-informed care; 3) Working within system constraints; and 4) Being trauma-informed. Preliminary effectiveness data included 177 participants (median age 2 years, and median total body surface area burn 1%). Causal assumptions within the logic model were unable to be fully tested, secondary to lower-than-expected adoption and fidelity. We found no significant difference for pain, distress and per-patient hospital care costs between groups (pre- and post-intervention). Future implementation strategies should include organizational support to keep a trauma-informed lens and to incorporate trauma-informed principles within a medical model of care. Despite efforts to co-design a staff education intervention and implementation approach focused on stakeholder engagement, adaptations are indicated to both the intervention and implementation strategies to promote uptake highlighting the complexity of changing clinician behaviours.

Metabolite profiling and bioactivity guided fractionation of Lactobacillaceae and rice bran postbiotics for antimicrobial-resistant Salmonella Typhimurium growth suppression.

Probiotic-fermented supplements (postbiotics) are becoming increasingly explored for their activity against antibiotic-resistant enteropathogens. Prebiotics are often incorporated into postbiotics to enhance their efficacy, but due to strain differences in probiotic activity, postbiotic antimicrobial effects are poorly understood. To improve postbiotic antimicrobial efficacy, we investigated and compared metabolite profiles of postbiotics prepared with three lactic acid bacteria strains (L. fermentum, L. paracasei, and L. rhamnosus) cultured with and without rice bran, a globally abundant, rich source of prebiotics. At their minimum inhibitory dose, L. fermentum and L. paracasei postbiotics + rice bran suppressed S. Typhimurium growth 42-55% more versus their respective probiotic-alone postbiotics. The global, non-targeted metabolome of these postbiotics identified 109 metabolites increased in L. fermentum and L. paracasei rice bran postbiotics, including 49 amino acids, 20 lipids, and 12 phytochemicals metabolites. To identify key metabolite contributors to postbiotic antimicrobial activity, bioactivity-guided fractionation was applied to L. fermentum and L. paracasei rice bran-fermented postbiotics. Fractionation resulted in four L. fermentum and seven L. paracasei fractions capable of suppressing S. Typhimurium growth more effectively versus the negative control. These fractions were enriched in 15 metabolites that were significantly increased in the global metabolome of postbiotics prepared with rice bran versus postbiotic alone. These metabolites included imidazole propionate (enriched in L. fermentum + rice bran, 1.61-fold increase; L. paracasei + rice bran 1.28-fold increase), dihydroferulate (L. fermentum + rice bran, 5.18-fold increase), and linoleate (L. fermentum + rice bran, 1.82-fold increase; L. paracasei + rice bran, 3.19-fold increase), suggesting that they may be key metabolite drivers of S. Typhimurium growth suppression. Here, we show distinct mechanisms by which postbiotics prepared with lactic acid bacteria and rice bran produce metabolites with antimicrobial activity capable of suppressing S. Typhimurium growth. Probiotic strain differences contributing to postbiotic antimicrobial activity attract attention as adjunctive treatments against pathogens.

Poor performance of paired tests of latent tuberculosis in highly immune-compromised individuals exposed to multidrug-resistant tuberculosis: time for new diagnostic markers.

Guideline-based recommendations for diagnosis of latent TB in highly immune suppressed populations are difficult to interpret and poorly characterised. More accurate biomarkers independent of T-cell functions are urgently required. https://bit.ly/41P8vTa.

Advancing randomized controlled trial methodologies: The place of innovative trial design in eating disorders research.

Randomized controlled trials can be used to generate evidence on the efficacy and safety of new treatments in eating disorders research. Many of the trials previously conducted in this area have been deemed to be of low quality, in part due to a number of practical constraints. This article provides an overview of established and more innovative clinical trial designs, accompanied by pertinent examples, to highlight how design choices can enhance flexibility and improve efficiency of both resource allocation and participant involvement. Trial designs include individually randomized, cluster randomized, and designs with randomizations at multiple time points and/or addressing several research questions (master protocol studies). Design features include the use of adaptations and considerations for pragmatic or registry-based trials. The appropriate choice of trial design, together with rigorous trial conduct, reporting and analysis, can establish high-quality evidence to advance knowledge in the field. It is anticipated that this article will provide a broad and contemporary introduction to trial designs and will help researchers make informed trial design choices for improved testing of new interventions in eating disorders. PUBLIC SIGNIFICANCE: There is a paucity of high quality randomized controlled trials that have been conducted in eating disorders, highlighting the need to identify where efficiency gains in trial design may be possible to advance the eating disorder research field. We provide an overview of some key trial designs and features which may offer solutions to practical constraints and increase trial efficiency.

Improving multidisciplinary management of patients living with obesity: The evaluation of seated bioimpedance measures and relationship to functional performance following targeted intervention.

Management of obesity requires a multidisciplinary approach including physical activity interventions, which have significant impacts on overall health outcomes. Greater levels of lean muscle mass are significantly associated with improved health and reduced risk of comorbidities and should be preserved where possible when undertaking rapid weight loss. This article reports on the physical and functional outcomes achieved during a 12-week intensive multidisciplinary intervention targeting obesity and evaluates correlations between body composition and functional outcomes. We additionally aimed to investigate the test-retest reliability and levels of agreement in body composition measurements using bioimpedance spectroscopy between seated and standing positions. Of the 35 participants included in analysis, significant differences were observed between baseline and post-intervention measures. These included weight loss of 12.6 kg, waist circumference reduction of 10.5 cm, fat mass reduction by 2.9%, muscle mass increase by 1.6%, 54.5 m improvement in the 6-minute walk test and 3.8 rep improvement in the 30-second sit-to-stand test. No significant correlations were observed between physical and functional outcome measures. Excellent test re-test reliability was observed in bioimpedance spectroscopy seated measurements (ICC >.9). Significant differences were observed between seated and standing bioimpedance spectroscopy measurements, however they are regarded as small differences in a clinical setting.

Pilot Study of Heat-Stabilized Rice Bran Acceptability in Households of Rural Southwest Guatemala and Estimates of Fiber, Protein, and Micro-Nutrient Intakes among Mothers and Children.

Nutrient-dense, acceptable foods are needed in low-resource settings. Rice bran, a global staple byproduct of white rice processing, is rich in amino acids, fibers, and vitamins, when compared to other cereal brans. This pilot study examines the nutritional contribution of rice bran to the daily diets of mother-child pairs in rural southwest Guatemala. Thirty households were screened. Mothers (≥18 years) and children (6 to 24 months) completed 24 h dietary recalls at baseline and after 12 weeks (endline) for diet intake and diversity analyses. During biweekly visits for 12 weeks, households with <5 members received 14 packets containing 60 g of heat-stabilized rice bran, and those with ≥5 members received 28 packets. The macro- and micro-nutrient contributions of rice bran and whole, cooked black beans were included in dietary simulation models with average intakes established between the recalls and for comparison with dietary reference intakes (DRIs). A baseline child food frequency questionnaire was administered. The 27 mothers and 23 children with complete recalls were included in analyses. Daily maternal consumption of 10 g/d of rice bran plus 100 g/d of black beans resulted in all achieving at least 50% of the fiber, protein, magnesium, niacin, potassium, and thiamin DRIs. Daily child consumption of 3 g/d of rice bran plus 10 g/d of black beans resulted in all achieving at least 50% of the magnesium, niacin, phosphorous, and thiamine DRIs. For 15/17 food categories, male children had a higher intake frequency, notably for animal-source foods and coffee. Dietary rice bran coupled with black beans could improve nutritional adequacy, especially for fiber and key micro-nutrients, with broader implications for addressing maternal and child malnutrition in low-resource settings.

Urine and Dried Blood Spots From Children and Pregnant Women Reveal Phytochemicals, Amino Acids, and Carnitine Metabolites as Cowpea Consumption Biomarkers.

SCOPE: Legumes consumption has been proven to promote health across the lifespan; cowpeas have demonstrated efficacy in combating childhood malnutrition and growth faltering, with an estimated malnutrition prevalence of 35.6% of children in Ghana. This cowpea feeding study aimed to identify a suite of metabolic consumption biomarkers in children and adults. METHODS AND RESULTS: Urine and dried blood spots (DBS) from 24 children (9-21 months) and 21 pregnant women (>18 years) in Northern Ghana are collected before and after dose-escalated consumption of four cowpea varieties for 15 days. Untargeted metabolomics identified significant increases in amino acids, phytochemicals, and lipids. The carnitine metabolism pathway is represented by 137 urine and 43 DBS metabolites, with significant changes to tiglylcarnitine and acetylcarnitine. Additional noteworthy candidate biomarkers are mansouramycin C, N-acetylalliin, proline betaine, N2, N5-diacetylornithine, S-methylcysteine, S-methylcysteine sulfoxide, and cis-urocanate. S-methylcysteine and S-methylcysteine sulfoxide are targeted and quantified in urine. CONCLUSION: This feeding study for cowpea biomarkers supports the utility of a suite of key metabolites classified as amino acids, lipids, and phytochemicals for dietary legume and cowpea-specific food exposures of global health importance.

Solutions to Enhance Health with Alternative Treatments (SEHAT) protocol: a double-blinded randomised controlled trial for gut microbiota-targeted treatment of severe acute malnutrition using rice bran in ready-to-use therapeutic foods in Indonesia.

INTRODUCTION: Current formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes. METHODS AND ANALYSIS: A total of 200 children aged 6-59 months with uncomplicated SAM (weight-for-height z-scores (WHZ) <-3, or mid-upper arm circumference (MUAC) <115 mm or having bilateral pitting oedema +/++) or approaching SAM (WHZ<-2.5) will be enrolled in a double-blinded, randomised controlled trial. Children in the active control arm will receive a locally produced RUTF; those in the intervention arm will receive the local RUTF with 5% rice bran. Children will receive daily RUTF treatment for 8 weeks and be monitored for 8 weeks of follow-up. Primary outcomes include the effectiveness of RUTF as measured by changes in weight, WHO growth z-scores, MUAC and morbidity. Secondary outcomes include modulation of the gut microbiome and dried blood spot metabolome, the percentage of children recovered at weeks 8 and 12, and malnutrition relapse at week 16. An intention-to-treat analysis will be conducted for each outcome. ETHICS AND DISSEMINATION: The findings of this trial will be submitted to peer-reviewed journals and will be presented at relevant conferences. Ethics approval obtained from the Medical and Health Research Ethical Committee at the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Madain Yogyakarta Ref. No.: KE/FK/0546/EC/2022 and KE/FK/0703/EC/2023 and from Colorado State University IRB#1823, OHRP FWA00000647. TRIAL REGISTRATION NUMBER: NCT05319717.

Follicle Stimulating Hormone (FSH) as a Predictor of Decreased Oocyte Yield in Patients with Normal Anti-Müllerian Hormone (AMH) and Antral Follicle Count (AFC).

Background: The purpose of the current study was to determine the utility of early follicular phase follicle-stimulating hormone (FSH) testing in patients undergoing in vitro fertilization (IVF). Methods: This was a retrospective review of patients from 2012 to 2015 at Mayo Clinic in Rochester, Minnesota, USA. Included subjects had a normal anti-Müllerian hormone (AMH) of 1 to 9 ng/ml and antral follicle count (AFC) of 10 to 29. Patients were stratified by FSH level when associated estradiol was less than 50 ng/ml. In total, 225 patients were categorized into three groups: high FSH (FSH ≥10 IU/L; n= 36), normal FSH (>5 IU/L and <10 IU/L; n=170), and low FSH (FSH ≤5 IU/L; n= 19). ANOVA and multiple logistic regression were used for statistical comparisons and for evaluation of the relationships between variables; significance level was set at <0.05. Results: There were no significant differences in demographics, IVF cycle type, or peak estradiol level between the groups. Patients with a high basal FSH level had a similar clinical pregnancy rate and live birth rate compared to controls and patients with low FSH. High FSH level was associated with decreased follicular development (17 versus 22; p<0.01), oocyte yield (15 versus 18; p=0.02), and embryo yield (8 versus 10; p=0.04) despite higher total doses of gonadotropins. Conclusion: Patients with normal AMH and AFC levels could be further stratified into lower responders and starting doses of medications can be adjusted based on high basal FSH levels. Therefore, it is suggested to counsel patients on pregnancy outcomes which seem to be quite similar regardless of the FSH level.

Partnering with consumers to co-design a person-centred coding framework for qualitative patient experience data.

BACKGROUND: Patient Reported Experience Measures (PREMs) provide health organisations insight into how 'person-centric' care is. Qualitative data in PREMs surveys provide essential context about experience but are challenging to analyse at an organisational level. OBJECTIVE: To co-design a person-centred coding framework to assist in the analysis of qualitative PREMs data. PATIENT INVOLVEMENT: Consumer representatives were involved in problem identification, co-design, coding of raw data (testing), evaluation and manuscript authorship. METHODOLOGY: Co-design principles guided production of a deductive coding framework with Picker Principles of Person-Centred Care as a conceptual framework. The framework was co-designed over 4 stages, with cross-professional stakeholders (including two consumer representatives): 1) assessment of current state and understanding priorities; 2) adapting Picker Principles of Person-Centred Care as a coding framework; 3) testing and evaluation of a coding template over two quality improvement (QI) cycles against measures of inter-coder reliability and perceived usefulness; 4) endorsement and planning for implementation. RESULTS: The Picker Principles were a suitable coding framework for inpatient PREMs data, and a coding template in an electronic spreadsheet met end-user needs. Results of the first QI cycle indicated a need for 'less academic' domain names and definitions, which were reviewed and updated to a first-person perspective in partnership with a consumer representative. Inter-coder reliability measures and qualitative feedback improved after cycle two testing and evaluation. DISCUSSION: This single site study produced a feasible solution to apply person-centred principles to analyse PREMs data and requires testing in different settings. Cross-disciplinary partnerships enabled the development of a reliable and acceptable deductive coding framework that was usable for people without prior experience in qualitative data analysis. PRACTICAL VALUE: Our solution offers an example for health services to harness the value of qualitative PREMs data and partner with consumers to take person-centric action to improve the safety, equity, and experience of healthcare.

Long-term Outcomes of Single and Dual En Bloc Kidney Transplants From Small Pediatric Donors: An ANZDATA Registry Study.

Kidney transplants from small pediatric donors are considered marginal and often transplanted as dual grafts. This study aimed to compare long-term outcomes between recipients of single kidney transplants (SKTs) and dual en bloc kidney transplants (EBKTs) from small pediatric donors. Methods: Data were obtained from the Australia and New Zealand Dialysis and Transplant Registry. All adult recipients of kidney transplants from donors aged ≤5 y were identified. The primary outcome of interest was death-censored graft survival by donor type. The secondary outcomes were early graft loss, delayed graft function, serum creatinine posttransplantation, acute rejection, and patient survival. Results: There were 183 adult recipients of kidney transplants from donors aged ≤5 y old. Of these, 60 patients had EBKT grafts, 79 patients had SKT grafts, and 44 patients had grafts of unknown type. Compared with SKT donors, EBKT donors had lower mean age (P < 0.001) and body weight (P < 0.001). There was no significant difference in death-censored graft survival between the groups, with median survival of 23.8 y (interquartile range 21.2-25) in the EBKT cohort and 21.8 y (11.6-26.8) in the SKT cohort (hazard ratio 1.3; 95% confidence interval, 0.59-2.64; P = 0.56). EBKT grafts had lower acute rejection rates than SKT grafts (P = 0.014). There was no significant difference observed between groups with respect to early graft loss, delayed graft function, posttransplantation serum creatinine posttransplantation, or patient survival. Conclusions: EBKT and SKTs from small pediatric donors are associated with excellent long-term graft survival rates.

Cognitive Aging in Older Breast Cancer Survivors.

BACKGROUND: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but the extant studies are limited in their intervals of assessment (two-five years). We studied the cognitive performance of a cohort of survivors and controls aged from 60 to 89 years utilizing cross-sectional cognitive performance data as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. METHODS: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5- to 15-year survivors (N = 328) and non-cancer controls (N = 158) were assessed at enrollment and at 8, 16, and 24 months with standard neuropsychological tests and comprehensive geriatric assessment. RESULTS: A cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower overall than controls in learning and memory (LM). Younger survivors, i.e., those under 75 years of age, exhibited lower performance in both LM and attention, and processing speed and executive function (APE), compared to controls, with no differences being observed between older survivors and controls, which tracked with deficit accumulation trends. CONCLUSION: Cognitive differences between the survivors and controls for the LM and APE domains were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.

Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors.

Dietary rice bran-mediated inhibition of colon carcinogenesis was demonstrated previously for carcinogen-induced rodent models via multiple anti-cancer mechanisms. This study investigated the role of dietary rice bran-mediated changes to fecal microbiota and metabolites over the time course of colon carcinogenesis and compared murine fecal metabolites to human stool metabolic profiles following rice bran consumption by colorectal cancer survivors (NCT01929122). Forty adult male BALB/c mice were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colon carcinogenesis and randomized to control AIN93M (n = 20) or diets containing 10% w/w heat-stabilized rice bran (n = 20). Feces were serially collected for 16S rRNA amplicon sequencing and non-targeted metabolomics. Fecal microbiota richness and diversity was increased in mice and humans with dietary rice bran treatment. Key drivers of differential bacterial abundances from rice bran intake in mice included Akkermansia, Lactococcus, Lachnospiraceae, and Eubacterium xylanophilum. Murine fecal metabolomics revealed 592 biochemical identities with notable changes to fatty acids, phenolics, and vitamins. Monoacylglycerols, dihydroferulate, 2-hydroxyhippurate (salicylurate), ferulic acid 4-sulfate, and vitamin B6 and E isomers significantly differed between rice bran- and control-fed mice. The kinetics of murine metabolic changes by the host and gut microbiome following rice bran consumption complemented changes observed in humans for apigenin, N-acetylhistamine, and ethylmalonate in feces. Increased enterolactone abundance is a novel diet-driven microbial metabolite fecal biomarker following rice bran consumption in mice and humans from this study. Dietary rice bran bioactivity via gut microbiome metabolism in mice and humans contributes to protection against colorectal cancer. The findings from this study provide compelling support for rice bran in clinical and public health guidelines for colorectal cancer prevention and control.

Multi-omics resources for targeted agronomic improvement of pigmented rice.

Pigmented rice (Oryza sativa L.) is a rich source of nutrients, but pigmented lines typically have long life cycles and limited productivity. Here we generated genome assemblies of 5 pigmented rice varieties and evaluated the genetic variation among 51 pigmented rice varieties by resequencing an additional 46 varieties. Phylogenetic analyses divided the pigmented varieties into four varietal groups: Geng-japonica, Xian-indica, circum-Aus and circum-Basmati. Metabolomics and ionomics profiling revealed that black rice varieties are rich in aromatic secondary metabolites. We established a regeneration and transformation system and used CRISPR-Cas9 to knock out three flowering time repressors (Hd2, Hd4 and Hd5) in the black Indonesian rice Cempo Ireng, resulting in an early maturing variety with shorter stature. Our study thus provides a multi-omics resource for understanding and improving Asian pigmented rice.

Reduced Serological Response to COVID-19 Booster Vaccine is Associated with Reduced B Cell Memory in Patients With Inflammatory Bowel Disease; VARIATION [VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS: This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS: Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

Cognitive function is mediated by deficit accumulation in older, long-term breast cancer survivors.

PURPOSE: This study aims to examine whether cognitive function in older, long-term breast cancer survivors is both a direct effect of cancer and cancer treatments and an indirect effect mediated by deficit accumulation. PATIENTS AND METHODS: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5-15-year survivors (N = 220) and age- and education-matched non-cancer controls (N = 123) were assessed at enrollment and at 8-, 16-, and 24-month follow-ups with standard neuropsychological tests and the comprehensive geriatric assessment which was used to calculate the deficit accumulation frailty index (DAFI). Blood or saliva samples for APOE genotyping were collected at enrollment. Participants were purposely recruited so that approximately 50% had a history of treatment with chemotherapy or and 50% were not exposed to chemotherapy. RESULTS: Latent variable mediation analysis revealed that cognitive performance was mediated by deficit accumulation for all three domains. The direct effect of cancer diagnosis and treatment history was significant for the Language domain (p = 0.04), a trend for the learning and memory domain (p = 0.054), and non-significant for the attention, processing speed, executive function (APE) domain. Carrying the APOE ε4 allele had a significant negative direct effect on the APE domain (p = 0.05) but no indirect effect through deficit accumulation. CONCLUSION: Cognitive function in older, long-term breast cancer survivors appears to be primarily mediated through deficit accumulation. IMPLICATIONS FOR CANCER SURVIVORS: These findings have important clinical implications suggesting that the most effective intervention to prevent or slow cognitive aging in older cancer survivors may be through prevention or management of comorbidities and interventions that maintain functional capacity (exercise, physical therapy) and social and mental health.

Immunity in Sea Turtles: Review of a Host-Pathogen Arms Race Millions of Years in the Running.

The immune system of sea turtles is not completely understood. Sea turtles (as reptiles) bridge a unique evolutionary gap, being ectothermic vertebrates like fish and amphibians and amniotes like birds and mammals. Turtles are ectotherms; thus, their immune system is influenced by environmental conditions like temperature and season. We aim to review the turtle immune system and note what studies have investigated sea turtles and the effect of the environment on the immune response. Turtles rely heavily on the nonspecific innate response rather than the specific adaptive response. Turtles' innate immune effectors include antimicrobial peptides, complement, and nonspecific leukocytes. The antiviral defense is understudied in terms of the diversity of pathogen receptors and interferon function. Turtles also mount adaptive responses to pathogens. Lymphoid structures responsible for lymphocyte activation and maturation are either missing in reptiles or function is affected by season. Turtles are a marker of health for their marine environment, and their immune system is commonly dysregulated because of disease or contaminants. Fibropapillomatosis (FP) is a tumorous disease that afflicts sea turtles and is thought to be caused by a virus and an environmental factor. We aim, by exploring the current understanding of the immune system in turtles, to aid the investigation of environmental factors that contribute to the pathogenesis of this disease and provide options for immunotherapy.

Butyrate limits human natural killer cell effector function.

The gut microbiota regulates chronic inflammation and has been implicated in the pathogenesis of a broad spectrum of disease including autoimmunity and cancer. Microbial short-chain fatty acids (SCFAs) e.g., butyrate have demonstrated immunomodulatory effects and are thought to be key mediators of the host-microbiome interaction. Here, we investigated the effect of butyrate on effector functions of blood derived human NK cells stimulated for 18 h with a combination of IL-12/IL-15, a potent mix of cytokines that drive NK cell activation. We show that butyrate has a strong anti-inflammatory effect on NK cells. NK cells cultured in the presence of butyrate expressed lower levels of activating receptors (TRAIL, NKp30, NKp44) and produced lower levels of cytokines (IFNγ, TNF-α, IL-22, granzyme B, granzyme A, perforin) in response to IL-12/IL-15. Butyrate restricted NK cell function by downregulation of mTORC1 activity, c-Myc mRNA expression and metabolism. Using a shotgun proteomic approach, we confirmed the effect of butyrate on NK cell cytokine signaling and metabolism and identified BRD2, MAT2A and EHD1 as downstream mediators of these effects. This insight into the immunomodulatory activity of butyrate on human NK cell function might help to develop new ways to limit NK cell function during chronic inflammation.

Remote, Computerised Cognitive Assessment for Breast Cancer- and Treatment-Related Cognitive Dysfunction: Psychometric Characteristics of the Cogsuite Neurocognitive Battery.

OBJECTIVE: Cancer-related cognitive dysfunction (CRCD) is a significant concern for breast cancer survivors. The Cogsuite battery was developed to improve sensitivity to CRCD with the use of cognitive experimental measures, clarify specific cognitive processes impacted and to be capable of being administered either in-office or remotely. METHODS: In sum, 357 breast cancer survivors and non-cancer controls completed the Cogsuite Battery in-office (n = 76) or remotely (n = 281). Measure validity, sensitivity to demographic factors, correlations with standard neuropsychological measures and intercorrelations of Cogsuite variables were assessed. Test-retest reliability was evaluated in-office (n = 24) and remotely (n = 80). RESULTS: Test-retest reliability for most variables assessed was adequate to strong. Internal validity, as indicated by the confirmation of expected condition effects within each measure, was established for all measures. Assessment of external validity found age, but not education, was a significant predictor in the majority of measures. Assessment of criterion validity found that Cogsuite variables were correlated with standard measures in psychomotor speed, working memory and executive function, but not associated with self-reported cognition or mood. CONCLUSIONS: Cogsuite is reliable and valid, and is sensitive to the effects of increasing age on cognition. The addition of the Cogsuite battery to standard assessment may improve sensitivity to CRCD and identify underlying processes that may be affected. Remote use of the Cogsuite battery in appropriate settings will lessen the burden for providers, researchers and survivors in research and clinical contexts.