Characterizing arginine, ornithine, and putrescine pathways in enteric pathobionts.

Arginine-ornithine metabolism plays a crucial role in bacterial homeostasis, as evidenced by numerous studies. However, the utilization of arginine and the downstream products of its metabolism remain undefined in various gut bacteria. To bridge this knowledge gap, we employed genomic screening to pinpoint relevant metabolic targets. We also devised a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics method to measure the levels of arginine, its upstream precursors, and downstream products in cell-free conditioned media from enteric pathobionts, including Escherichia coli, Klebsiella aerogenes, K. pneumoniae, Pseudomonas fluorescens, Acinetobacter baumannii, Streptococcus agalactiae, Staphylococcus epidermidis, S. aureus, and Enterococcus faecalis. Our findings revealed that all selected bacterial strains consumed glutamine, glutamate, and arginine, and produced citrulline, ornithine, and GABA in our chemically defined medium. Additionally, E. coli, K. pneumoniae, K. aerogenes, and P. fluorescens were found to convert arginine to agmatine and produce putrescine. Interestingly, arginine supplementation promoted biofilm formation in K. pneumoniae, while ornithine supplementation enhanced biofilm formation in S. epidermidis. These findings offer a comprehensive insight into arginine-ornithine metabolism in enteric pathobionts.

Music therapy for supporting informal carers of adults with life-threatening illness pre- and post-bereavement; a mixed-methods systematic review.

BACKGROUND: Music therapy interventions with informal carers of individuals with life-threatening illness at pre- and post-bereavement is an increasingly important clinical area. This systematic review is the first to synthesise and critically evaluate the international evidence associated with music therapy with adult informal carers pre- and post-bereavement. Specifically, the objectives were: i) to describe the characteristics and effectiveness of music therapy interventions which aim to improve health-related outcomes for adult informal carers of adults with life-threatening illness (pre- and post-bereavement), and ii) to describe the experience of music therapy for adult informal carers of adults with life-threatening illness (pre- and post-bereavement). METHODS: Eligibility: adult informal carers of adults at end of life or bereaved; music therapy interventions for improving health-related outcomes; qualitative; mixed-method; and quantitative studies including comparators of any other intervention; published in English from 1998 onwards. Six databases were searched up to July 2022. A JBI mixed-methods systematic review approach was followed throughout, including quality appraisal, data extraction and a convergent segregated approach to synthesis and integration. RESULTS: A total of 34 studies were included, published between 2003 and 2022. Most were conducted in North America (n = 13), Australia (n = 10), or Europe (n = 8). No studies were conducted in low- and middle-income countries or in the UK. The majority were qualitative (n = 17), followed by quasi-experimental (n = 8), mixed-methods (n = 7) and two RCTs. The majority focused on carers of individuals with dementia (n = 21) or advanced cancer (n = 7). Seventeen studies were purely quantitative or included a quantitative component. During meta-synthesis, findings were aligned to core outcomes for evaluating bereavement interventions in palliative care and previously identified risk factors for complicated grief. Commonly targeted outcomes in quantitative studies included quality of life and mental wellbeing, showing equivocal effectiveness of music therapy with significant and non-significant results. Twenty-two studies either purely qualitative or with a qualitative component underwent meta synthesis and suggested a diverse range of improved pre- and post-bereavement outcomes for informal carers across all core outcomes, and across all risk and protective factors, including psychological, spiritual, emotional, and social outcomes. CONCLUSIONS: Qualitative studies provide moderate to strong evidence for improved health-related outcomes for adult informal carers of adults with life-threatening illness pre-bereavement. Limited studies including those bereaved negates conclusions for the bereavement phase. Comparisons and explanations for effectiveness across quantitative and qualitative studies are equivocal, with a high risk of bias and small samples in the limited number of quantitative studies, demonstrating a need for high-quality RCTs. SYSTEMATIC REVIEW PRE-REGISTRATION: PROSPERO [CRD42021244859].

Αlpha-thalassemia: A practical overview.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and ß globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.

Treatment of vitamin D deficiency in children.

INTRODUCTION: Vitamin D deficiency affects from 10% to 50% in various pediatric population groups and causes life-threatening hypocalcemia in infants, crippling rickets in infants and children, and increased risk of subsequent adult metabolic and neurologic problems. AREAS COVERED: An English language literature search of PubMed was performed since 1940 as were the authors' personal literature collections. References identified in the reviewed literature are considered. DIAGNOSIS: The diagnosis of vitamin D deficiency is based on serum 25-hydroxyvitamin D levels. Clinical features of rickets include bone deformities and elevated alkaline phosphatase. Most children and adolescents who are biochemically vitamin D deficient do not have specific symptoms or signs of deficiency. PREVENTION: Prevention of vitamin D deficiency is via exposure to sunshine, food and beverage fortification, and dietary supplementation. TREATMENT: Effective treatment of vitamin D deficiency is via oral or injectable administration of vitamin D. Dosing and duration of vitamin D therapy have been described for healthy children and for children with underlying medical conditions, but recommendations vary. EXPERT OPINION: Further investigation is needed to determine long-term non-skeletal effects of childhood vitamin D deficiency, benefits of supplementation in asymptomatic individuals with biochemical vitamin D deficiency, and appropriate screening for vitamin D deficiency in asymptomatic children and adolescents.

A Health System Framework for Addressing Structural Racism: Mass General Brigham's United Against Racism Initiative.

The legacy of racism and structural inequality has taken a heavy toll on the health care system and the health outcomes of patients and members of community catchment areas. To achieve optimal health outcomes for all, health systems will need to enact structural change that is meaningful, measurable, and rooted in evidence. We describe an antiracism campaign organized into three pillars of focus (Leadership/Employees/Culture, Patient Care Equity, and Community Health and Policy Advocacy) and implemented across Mass General Brigham, a large integrated health system in the northeast of the United States. Our study ranges from the foundational to the aspirational and examples of data-driven areas of focus, programs (e.g., staff education, social risk mitigation, and new models of clinical service), and metrics developed for the health care workforce, patients, and surrounding communities are presented.

Low phytic acid pea supplementation as an approach to combating iron deficiency in female runners: A randomized control trial.

Background: Iron deficiency (ID) is the most prevalent micronutrient deficiency in the world and the leading cause of anemia globally. Female athletes are at a disproportionate risk for ID due to blood loss through menstruation and decreased iron absorption secondary to exercise. Field peas are a rich source of iron but, similar to iron from other plant-based sources, the iron has limited bioavailability due to high levels of phytic acid, an inherent compound that binds to cations, creating a salt (phytate), which limits absorption during digestion. Aim: The purpose of our research was to investigate the effect of a field pea variety bred to have low levels of phytic acid on plasma ferritin, exercise performance, and body composition in female runners. Methods: Twenty-eight female runners (age:34.6 ± 9.7 years; weight: 65.1 ± 8.1 kg; VO2max: 50.7 ± 8.9 ml/kg/min) underwent measures of ferritin, exercise performance, and body composition before and after being randomly assigned to consume a powder derived from regular peas, low phytic acid peas, or a non-pea control (maltodextrin), plus vitamin C for 8 weeks. Results: The regular pea and low phytic acid pea groups had a 14.4% and 5.1% increase in plasma ferritin, respectively, while the maltodextrin group had a decrease of 2.2%; however, the difference in changes between groups was not statistically significant. No differences between groups were evident in any of the other measures. Conclusion: Larger doses or longer duration of pea supplementation may be necessary to induce meaningful changes in iron status. This trial was registered at ClinicalTrials.gov (NCT04872140).

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Virtual Care Team Guided Management of Patients With Heart Failure During Hospitalization.

BACKGROUND: Scalable and safe approaches for heart failure guideline-directed medical therapy (GDMT) optimization are needed. OBJECTIVES: The authors assessed the safety and effectiveness of a virtual care team guided strategy on GDMT optimization in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In a multicenter implementation trial, we allocated 252 hospital encounters in patients with left ventricular ejection fraction ≤40% to a virtual care team guided strategy (107 encounters among 83 patients) or usual care (145 encounters among 115 patients) across 3 centers in an integrated health system. In the virtual care team group, clinicians received up to 1 daily GDMT optimization suggestion from a physician-pharmacist team. The primary effectiveness outcome was in-hospital change in GDMT optimization score (+2 initiations, +1 dose up-titrations, -1 dose down-titrations, -2 discontinuations summed across classes). In-hospital safety outcomes were adjudicated by an independent clinical events committee. RESULTS: Among 252 encounters, the mean age was 69 ± 14 years, 85 (34%) were women, 35 (14%) were Black, and 43 (17%) were Hispanic. The virtual care team strategy significantly improved GDMT optimization scores vs usual care (adjusted difference: +1.2; 95% CI: 0.7-1.8; P < 0.001). New initiations (44% vs 23%; absolute difference: +21%; P = 0.001) and net intensifications (44% vs 24%; absolute difference: +20%; P = 0.002) during hospitalization were higher in the virtual care team group, translating to a number needed to intervene of 5 encounters. Overall, 23 (21%) in the virtual care team group and 40 (28%) in usual care experienced 1 or more adverse events (P = 0.30). Acute kidney injury, bradycardia, hypotension, hyperkalemia, and hospital length of stay were similar between groups. CONCLUSIONS: Among patients hospitalized with HFrEF, a virtual care team guided strategy for GDMT optimization was safe and improved GDMT across multiple hospitals in an integrated health system. Virtual teams represent a centralized and scalable approach to optimize GDMT.

Effects of dietary sulfur amino acid levels on growth performance and intestinal immunity in broilers vaccinated and subsequently infected with coccidiosis.

Coccidia vaccination is a common practice in the poultry industry. However, research is lacking regarding the optimal nutritional support for coccidia vaccinated broilers. In this study, broilers were vaccinated with coccidia oocyst at hatch and were fed with a common starter diet from 1 to 10 d. On d 11, the broilers were randomly assigned to groups in a 4 × 2 factorial arrangement. Briefly, the broilers were fed one of four diets containing 0.6, 0.8, 0.9, and 1.0% of standardized ileal digestible methionine plus cysteine (SID M+C), respectively, from 11 to 21 d. On d 14, the broilers from each diet group were orally gavaged with either PBS (Mock challenge) or Eimeria oocysts. Compared to PBS-gavaged broilers and regardless of dietary SID M+C levels, the Eimeria-gavaged broilers had 1) decreased gain-to-feed ratio (15-21 d, P = 0.002; 11-21 d, P = 0.011); 2) increased fecal oocysts (P < 0.001); 3) increased plasma anti-Eimeria IgY (P = 0.033); and 4) increased intestinal luminal interleukin-10 (IL-10; duodenum, P = 0.039; jejunum, P = 0.018) and gamma interferon (IFN-γ; duodenum, P < 0.001; jejunum, P = 0.017). Regardless of Eimeria gavage, broilers fed 0.6% SID M+C had decreased (P<0.001) body weight gain (15-21 and 11-21 d) and gain-to-feed ratio (11-14, 15-21, and 11-21 d) when compared to those fed ≥ 0.8% SID M+C. Eimeria challenge increased (P < 0.001) duodenum lesions when the broilers were fed with 0.6, 0.8, and 1.0% SID M+C, and increased (P = 0.014) mid-intestine lesions when the broilers were fed with 0.6 and 1.0% SID M+C. An interaction between the two experimental factors was detected on plasma anti-Eimeria IgY titers (P = 0.022), as coccidiosis challenge increased plasma anti-Eimeria IgY titers only when the broilers were fed with 0.9% SID M+C. In summary, the dietary SID M+C requirement for grower (11-21 d) broilers vaccinated with coccidiosis was ranged from 0.8 to 1.0% for optimal growth performance and intestinal immunity, regardless of coccidiosis challenge.

Neural and behavioral adaptations to frontal theta neurofeedback training: A proof of concept study.

Previous neurofeedback research has shown training-related frontal theta increases and performance improvements on some executive tasks in real feedback versus sham control groups. However, typical sham control groups receive false or non-contingent feedback, making it difficult to know whether observed differences between groups are associated with accurate contingent feedback or other cognitive mechanisms (motivation, control strategies, attentional engagement, fatigue, etc.). To address this question, we investigated differences between two frontal theta training groups, each receiving accurate contingent feedback, but with different top-down goals: (1) increase and (2) alternate increase/decrease. We hypothesized that the increase group would exhibit greater increases in frontal theta compared to the alternate group, which would exhibit lower frontal theta during down- versus up-modulation blocks over sessions. We also hypothesized that the alternate group would exhibit greater performance improvements on a Go-NoGo shooting task requiring alterations in behavioral activation and inhibition, as the alternate group would be trained with greater task specificity, suggesting that receiving accurate contingent feedback may be the more salient learning mechanism underlying frontal theta neurofeedback training gains. Thirty young healthy volunteers were randomly assigned to increase or alternate groups. Training consisted of an orientation session, five neurofeedback training sessions (six blocks of six 30-s trials of FCz theta modulation (4-7 Hz) separated by 10-s rest intervals), and six Go-NoGo testing sessions (four blocks of 90 trials in both Low and High time-stress conditions). Multilevel modeling revealed greater frontal theta increases in the alternate group over training sessions. Further, Go-NoGo task performance increased at a greater rate in the increase group (accuracy and reaction time, but not commission errors). Overall, these results reject our hypotheses and suggest that changes in frontal theta and performance outcomes were not explained by reinforcement learning afforded by accurate contingent feedback. We discuss our findings in terms of alternative conceptual and methodological considerations, as well as limitations of this research.

Psychotherapists' openness to engage their patients in Psilocybin-Assisted Therapy for mental health treatment.

Despite psychedelic research initially ceasing in the 1970-80s, the findings documented encouraged researchers to re-examine the safety and efficacy of treating mental health with psychedelics. Of particular focus, psilocybin has shown to have therapeutic potential for a variety of mental health problems and was granted breakthrough therapy status by the FDA. Should psilocybin eventually become legally licensed, the success of Psilocybin-Assisted Therapy (PAT) may largely rely on clinicians' openness to engage their eligible patients with PAT. We therefore assessed 119 psychologists' openness to recommend PAT, perceived barriers/facilitators to informing patients about PAT, and factors affecting their openness to involve patients with PAT if FDA approved. While 77.4 % of psychologists agreed they would inform eligible patients about PAT, 91.6 % stated they would still recommend psychotherapies that do not involve psilocybin first. 76.5 % endorsed that knowledge on psilocybin would increase their likelihood to inform patients about PAT. More positive attitudes and beliefs about psilocybin, greater self-reported knowledge of psilocybin, personal history of psychedelic usage, and more positive attitudes towards medical cannabis (MC) was associated with greater openness to engage patients with PAT. Our regression analysis revealed that attitudes towards MC and beliefs about psilocybin were the only significant predictors of psychotherapists' openness towards PAT. These findings provide relevant information to institutions planning educational programs for mental health professionals about psilocybin and Psychedelic-Assisted Therapies.

Specialized metabolism by trichome-enriched Rubisco and fatty acid synthase components.

Acylsugars, specialized metabolites with defense activities, are secreted by trichomes of many solanaceous plants. Several acylsugar metabolic genes (AMGs) remain unknown. We previously reported multiple candidate AMGs. Here, using multiple approaches, we characterized additional AMGs. First, we identified differentially expressed genes between high- and low-acylsugar-producing F2 plants derived from a cross between cultivated tomato (Solanum lycopersicum) and a wild relative (Solanum pennellii), which produce acylsugars that are ∼1% and ∼20% of leaf dry weight, respectively. Expression levels of many known and candidate AMGs positively correlated with acylsugar amounts in F2 individuals. Next, we identified lycopersicum-pennellii putative orthologs with higher nonsynonymous to synonymous substitutions. These analyses identified four candidate genes, three of which showed enriched expression in stem trichomes compared to underlying tissues (shaved stems). Virus-induced gene silencing confirmed two candidates, Sopen05g009610 [beta-ketoacyl-(acyl-carrier-protein) reductase; fatty acid synthase component] and Sopen07g006810 (Rubisco small subunit), as AMGs. Phylogenetic analysis indicated that Sopen05g009610 is distinct from specialized metabolic cytosolic reductases but closely related to two capsaicinoid biosynthetic reductases, suggesting evolutionary relationship between acylsugar and capsaicinoid biosynthesis. Analysis of publicly available datasets revealed enriched expression of Sopen05g009610 orthologs in trichomes of several acylsugar-producing species. Similarly, orthologs of Sopen07g006810 were identified as solanaceous trichome-enriched members, which form a phylogenetic clade distinct from those of mesophyll-expressed "regular" Rubisco small subunits. Furthermore, δ13C analyses indicated recycling of metabolic CO2 into acylsugars by Sopen07g006810 and showed how trichomes support high levels of specialized metabolite production. These findings have implications for genetic manipulation of trichome-specialized metabolism in solanaceous crops.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients.

Background: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS. Methods: Atovaquone was extracted from a 10 µL volume of K2-EDTA human plasma using a solution consisting of ACN: EtOH: DMF (8:1:1 v:v:v), separated using reverse-phase chromatography, and detected using a SCIEX 5500 QTrap MS system. LC-MS/MS assay performance was evaluated for precision, accuracy, carryover, sensitivity, specificity, linearity, and interferences. Results: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min per injection, and retention times of 4.3 min. Atovaquone was measured over a dynamic concentration range of 0.63 - 80 µM with a deviation within ≤ ± 5.1 % of the target value. Intra- and inter-assay precision were ≤ 2.7 % and ≤ 8.4 %, respectively. Dilutional, carryover, and interference studies were also within acceptable limits. Conclusions: Our studies have shown that our LC-MS/MS-based method is both reliable and robust for the quantification of plasma atovaquone concentrations and can be used to determine the effective dose of atovaquone for pediatric patients treated for AML.

A simple daily dynamic feeding regimen for reducing phosphorus consumption and excretion in laying hens.

Phosphorus metabolism in laying hens is a highly dynamic process over the course of the 24 h egg-laying cycle. Adjusting the phosphorus feeding regimen according to the daily egg-laying cycle may help to improve phosphorus utilization efficiency. Hy-Line Brown layers (n = 120; 70 wk old) were offered 4 different phosphorus daily regimens: (1) RR, fed regular phosphorus at both 09:00 and 17:00; (2) RL, fed regular phosphorus at 09:00 and low phosphorus at 17:00; (3) LR, fed low phosphorus at 09:00 and regular phosphorus at 17:00; (4) LL, fed low phosphorus at both 09:00 and 17:00. The regular and low phosphorus diets contained 0.32% and 0.14% non-phytate phosphorus, respectively. The feeding trial lasted for 12 wk. As a result, layers on the RL regimen had decreased laying rate (P < 0.05; 5 to 8, 9 to 12, and 1 to 12 wk) when compared to all other regimens. Layers on the LL regimen had decreased eggshell thickness and specific gravity (P < 0.05; wk 8) when compared to all other regimens, and had decreased egg shell strength (P < 0.05; wk 8) when compared to RL and LR regimens. When compared to the RR regimen (a common practice in the industry), layers on the LR regimen had: (1) identical laying performance and egg quality (P > 0.05); (2) decreased phosphorus excretion (P < 0.05) during the period of 09:00 to 17:00; (3) increased jejunal calbindin D28k protein expression (P < 0.05) 2 h after feeding in the morning; (4) decreased serum fibroblast growth factor 23 and calcitriol levels (P < 0.05), decreased jejunal type III sodium-phosphate cotransporter 2 gene and protein expression (P < 0.05), and decreased renal type III sodium-phosphate cotransporter 1 protein expression (P < 0.05), 2 h after feeding in the afternoon. In summary, when dietary phosphorus was supplemented in accordance with daily serum phosphorus rhythms (i.e., the LR regimen), laying performance and egg quality were well supported whilst significantly decreasing phosphorus consumption and excretion. Thus, serum phosphorus rhythms will need to be carefully maintained when developing dietary phosphorus-reduction strategies in laying hens.

A systematic review of the impact of housing on sow welfare during post-weaning and early pregnancy periods.

Breeder animals are an important focus in farm animal welfare assessments as they typically live the longest lives and are at the greatest risk for suffering due to their longevity. For breeding pigs, the time between the end of lactation (post-weaning) and the implantation of embryos (early gestation) is very dynamic from both a physiological and husbandry perspective. However, research to date is limited on how best to house and manage sows during this critical period of their production cycle from a welfare perspective. Previous animal-based welfare outcome measures were restricted to certain health, behavioral and physiological indicators. This systematic review used Web of Science to make in-depth comparisons among welfare-based studies that focus on sow housing during the post-weaning and early pregnancy period to identify important knowledge gaps. Only a small number of studies (n = 27) were found that met our systematic search criteria. Compared to stalls, group housing requires mixing of animals and always triggers more aggression and skin lesions at the time of mixing. The predominant use of health and physiological indicators constrained the animal-based welfare outcomes in these studies. Thus, what type of housing yields the best overall welfare outcome remains to be elucidated as none of the studies found explored the mental wellbeing of sows during this period. This systematic review defines a critical knowledge gap regarding the full impact of housing on the welfare of post-weaning and early gestation sows. This gap, and thus the true welfare impact of sow housing, will only be addressed by the use of novel, more holistic assessment methods that also capture the psychological state of the sow.

Dietary supplementation of sulfur amino acids improves intestinal immunity to Eimeria in broilers treated with anti-interleukin-10 antibody.

Oral antibody to interleukin-10 (anti-IL-10) enhances the intestinal immune defense against Eimeria. The sulfur amino acids methionine and cysteine (M+C) play essential roles in inducing and maintaining protective immune responses during intestinal infections. Hence, increased dietary M+C may support the anti-IL-10-induced intestinal immunity to Eimeria. Broilers (n = 640) were arranged in a 2 × 2 × 2 factorial design with 2 levels of each of the 3 main factors: dietary standardized ileal digestible (SID) M+C levels (0.6% or 0.8%), dietary anti-IL-10 supplementation (with or without), and coccidiosis challenge (control or challenge). Briefly, the broilers were supplied with either 0.6% or 0.8% SID M+C, each with or without anti-IL-10 (300 µg/kg), from d 10 to 21. On d 14, broilers from each diet were gavaged with either PBS or Eimeria. The resulting Eimeria infection induced fecal oocyst shedding and intestinal lesions. Broilers fed 0.8% SID M+C (main effects, P ≤ 0.05) had decreased feed-to-gain ratio, increased duodenum and cecum luminal anti-Eimeria IgA titers, and decreased fecal oocyst counts, when compared to 0.6% SID M+C. The supplementation of anti-IL-10 (main effects, P ≤ 0.05) increased cecum luminal total IgA concentration and decreased cecum lesions. Interactions (P ≤ 0.05) were detected for growth performance and cecum luminal IFN-γ. Briefly, the highest body weight gain and feed intake were reached in PBS-gavaged broilers fed 0.8% SID M+C with no anti-IL-10 and in Eimeria-challenged broilers fed 0.8% SID M+C with anti-IL-10. In Eimeria-infected broilers, anti-IL-10 increased intestinal luminal IFN-γ and body weight gain only at 0.8% SID M+C. Collectively, anti-IL-10 increased intestinal luminal IFN-γ levels, decreased cecum lesions and restored growth only when fed with adequate amounts of sulfur amino acids. Our findings underscore the importance of providing sufficient essential nutrients to support the anti-IL-10 induced immunity against coccidiosis.

Effects of caffeine, methylliberine, and theacrine on vigilance, marksmanship, and hemodynamic responses in tactical personnel: a double-blind, randomized, placebo-controlled trial.

Background: Tactical athletes require fast reaction times (RT) along with high levels of vigilance and marksmanship performance. Caffeine has been shown to improve these measures but also results in increased blood pressure and jitteriness. Research on other purine alkaloids, such as methylliberine and theacrine, has suggested they do not increase blood pressure or jitteriness to the same extent, but their impact on tactical performance is unknown. Methods: A between-subjects, randomized, placebo-controlled design was used to test the effects of placebo (PLA), 300 mg caffeine (CAF), and a combination of 150 mg caffeine, 100 mg methylliberine, and 50 mg theacrine (CMT) on RT and marksmanship along with hemodynamic and arousal measures following a sustained vigilance task in tactical personnel (n = 48). Following consumption of the supplement, participants underwent a 150-min protocol consisting of two rounds. Each round began with leisurely reading followed by a 30-min vigilance task before beginning two trials of movement and marksmanship tasks. Hemodynamics and felt arousal were assessed throughout the protocol. Composite Z-scores were calculated for overall performance measures at each timepoint, and mixed-effects models were used to assess differences in RT, accuracy, and composite Z-scores along with hemodynamics and felt arousal. An α-level of 0.05 was used to determine statistical significance, and Cohen's d was used to quantify effect sizes. Results: A Group-by-Time interaction for vigilance RT (P = 0.038) indicated improvements for both CAF and CMT from round 1 to round 2 (P < 0.01) while PLA did not change (P = 0.27). No Group main effects or Group-by-Time interactions were found for movement or marksmanship performance (P > 0.20). Group main effects for systolic (SBP; P = 0.001) and diastolic blood pressure (DBP; P = 0.028) indicated higher SBP in CAF (P = 0.003, d= 0.84) and CMT (P = 0.007, d= 0.79) compared to PLA but only higher DBP in CAF (P = 0.025, d= 0.74). No Group-by-Time interaction or Group main effect was found for felt arousal (P > 0.16). Conclusions: These findings suggest similar benefits on RT during a vigilance task between CAF, containing 300 mg caffeine, and CMT above PLA, though CAF resulted in slightly less favorable hemodynamic changes. This study is the first to provide data showing similar efficacy of combined caffeine, methylliberine, and theacrine compared to double the caffeine dose consumed alone on vigilance RT but without a significant rise in DBP above PLA in tactical personnel.

Development, Validation, and Evaluation of the Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index From the ImageKids Study.

BACKGROUND & AIMS: Cross-sectional imaging is important in the assessment of transmural inflammation in Crohn's disease (CD). Small bowel involvement is often more extensive in pediatric CD, requiring a panentering measuring tool. We undertook to develop a magnetic resonance enterography (MRE)-based index that would measure inflammation in all segments of the intestine, without rectal contrast. METHODS: Children with CD underwent ileocolonoscopy and MRE and half were prospectively followed for 18 months when MRE was repeated. Item generation and reduction were performed by a Delphi panel of pediatric radiologists, a systematic literature review, a cross-sectional study of 48 MREs, and a steering committee. Formatting and weighting were performed using multivariate modeling adjusted by a steering committee. MREs were read locally and centrally. Reliability, validity, and responsiveness were determined using several clinimetric and psychometric approaches. RESULTS: Thirty items were initially generated and reduced to 5 using regression analysis on 159 MREs: wall thickness, wall diffusion weighted imaging, ulcerations, mesenteric edema, and comb sign. In the validation cohort of 81 MREs, the weighted global PICMI correlated well with the radiologist global assessment (r = 0.85; P < .001) and with the simple endoscopic score in a subsample with ileocolonic disease (r = 0.63; P < .001). Interobserver and test-retest reliability were high (interclass correlation coefficients, 0.84; 95% confidence interval [CI], 0.79-0.87; and 0.81, 95% CI, 0.65-0.90, respectively; both P < .001). Excellent responsiveness was found at repeated visits (n = 116 MREs; area under the receiver operating characteristic curve 0.96; 95% CI, 0.93-0.99). Transmural healing was defined as PICMI ≤10 and response as a change of >20 points with excellent discriminative validity (area under the receiver operating characteristic curve = 0.96; 95% CI, 0.93-0.99). CONCLUSIONS: The PICMI is a valid, reliable, and responsive index for assessing transmural inflammation in pediatric CD. It scores the entire bowel length and does not require intravenous contrast or rectal enema and, therefore, is suitable for use in children. (ClinicalTrials.gov, Number: NCT01881490.).