Modeling Sex-Bias in Anxiety: Pros and Cons of a Larval Zebrafish Model.

Anxiety disorders are the most prevalent psychiatric disorders, exhibiting strong female bias. Clinical studies implicate declining estradiol levels in the exacerbation of anxiety symptoms in the premenstrual phase of the menstrual cycle. This study aimed to simulate estradiol fluctuation-linked anxiety behavior in larval zebrafish, using an estradiol treatment withdrawal model. Contrary to model aims, estradiol treatment withdrawal decreased both basal activity and anxiety-like hyperlocomotion (ANOVA main effect of dose, P < 0.0001 and P < 0.01, respectively) in the light/dark transition test. The accuracy of the estradiol washout model was not improved by longer durations of treatment or withdrawal. Basal activity was slightly altered by supraphysiological concentrations of WAY-200070 in the absence of added estradiol. Estrogen receptor (ER) ß expression was not upregulated in larvae exposed to physiologically relevant, low concentrations of estradiol. Longer exposure to low concentrations of estradiol increased antioxidant capacity (P < 0.01). In addition, acute exposure to low concentrations of estradiol increased basal activity. Data suggest that in the current models, estradiol-associated altered activity levels were linked to more favorable redox status, rather than reflecting altered anxiety levels. As such, it is recommended that zebrafish larval behavioral analysis be conducted in parallel with mechanistic studies such as redox indicators, for investigations focused on ER signaling.

Analysis of spontaneous cytomegalovirus clearance after low level reactivation using a pre-emptive treatment threshold of 4,000 IU/mL in allogeneic hematopoietic cell transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) can be a serious complication after allogeneic hematopoietic cell transplant (HCT). CMV viral load is routinely monitored, and pre-emptive therapy is initiated to prevent CMV viremia from developing into CMV organ disease based on institutional thresholds. There is no established universal threshold for pre-emptive therapy and many centers utilize different strategies. METHODS: Allogeneic HCT recipients at WVU Medicine from 2009 to 2021 were routinely initiated on pre-emptive CMV treatment for a PCR viral threshold above 4000 IU/mL. Adult patients with quantifiable values below this threshold, were analyzed to evaluate the rate of spontaneous clearance without initiation of CMV-directed therapy, during their first episode of CMV reactivation. This study excluded any patients that received letermovir prophylaxis. RESULTS: Sixty patients were included in the analysis. The spontaneous clearance rate was 60 %. The risk factors that were associated with a lower spontaneous clearance rate were reactivation within thirty days after transplant (p = 0.031), presence of graft-versus-host-disease (p = 0.031), and CMV PCR values of 2500-4000 IU/mL (p = 0.02). Although these patients had lower rates of spontaneous clearance, they still spontaneously cleared in 42 %, 42 %, and 43 % of the cases, respectively. CONCLUSION: Delaying pre-emptive treatment until a CMV PCR value of 4000 IU/mL is reached appears appropriate and decreases unnecessary treatment toxicity and resistance.

Evaluation of prolonged magnesium infusion after allogeneic hematopoietic cell transplant.

PURPOSE: Calcineurin inhibitor use after allogeneic hematopoietic cell transplantation (allo-HCT) is associated with significant magnesium wasting. Utilization of a prolonged magnesium infusion is thought to lead to a lower serum peak concentration and therefore, decreased renal wasting of magnesium. In November 2017, our institution implemented a modification to our inpatient electrolyte replacement protocol for allo-HCT recipients that extended the magnesium infusion rate from 4 g/2 h to 4 g/4 h based on this theoretical advantage. The primary objective of this study was to compare the median magnesium requirements per day of admission between patients who received magnesium 4 g/2 h to patients who received magnesium 4 g/4 h. Secondary objectives included a comparison of the per-patient median serum magnesium concentration during admission, as well as the median incremental difference in serum magnesium concentration after intravenous replacement per patient per admission. METHODS: Allo-HCT recipients who received prolonged infusion magnesium infusions were compared to a historical cohort of allo-HCT patients who received shorter IV magnesium infusions. Admissions were included if the patient had received an allo-HCT within 100 days prior, was admitted to the Transplant and Cellular Therapy Unit at WVU Medicine J.W. Ruby Memorial Hospital, and received at least one magnesium infusion and one dose of cyclosporine or tacrolimus. Admissions were excluded if the patient received oral magnesium, total parenteral nutrition, aminoglycosides, amphotericin, carboplatin, cisplatin, or foscarnet. RESULTS: The pre-implementation group consisted of 81 admissions (n = 64 patients), while the post-implementation group consisted of 90 admissions (n = 60 patients). Median magnesium requirements per day of admission were not different between groups at 1.4 g of magnesium in the pre-implementation group and 1.9 g of magnesium in the post-implementation group (P = 0.25). Median serum magnesium concentrations and median incremental difference in serum magnesium concentration after intravenous replacement were also not different between groups: 1.65 mg/dL vs 1.60 mg/dL (P = 0.65) and 0.30 mg/dL vs 0.28 mg/dL (P = 0.67), respectively. CONCLUSIONS: Prolonged infusion of magnesium in allo-HCT recipients receiving CNI therapy does not result in improvement in magnesium retention.

Microbiome of Ceca from Broiler Chicken Vaccinated or Not against Coccidiosis and Fed Berry Pomaces.

American cranberry (Vaccinium macrocarpon) and lowbush/wild blueberry (V. angustifolium) pomace are polyphenol-rich products having potentially beneficial effects in broiler chickens. This study investigated the cecal microbiome of broiler-vaccinated or non-vaccinated birds against coccidiosis. Birds in each of the two groups (vaccinated or non-vaccinated) were fed a basal non-supplemented diet (NC), a basal diet supplemented with bacitracin (BAC), American cranberry (CP), and lowbush blueberry (BP) pomace alone or in combination (CP + BP). At 21 days of age, cecal DNA samples were extracted and analyzed using both whole-metagenome shotgun sequencing and targeted-resistome sequencing approaches. Ceca from vaccinated birds showed a lower abundance of Lactobacillus and a higher abundance of Escherichia coli than non-vaccinated birds (p < 0.05). The highest and lowest abundance of L. crispatus and E. coli, respectively, were observed in birds fed CP, BP, and CP + BP compared to those from NC or BAC treatments (p < 0.05). Coccidiosis vaccination affected the abundance of virulence genes (VGs) related to adherence, flagella, iron utilization, and secretion system. Toxin-related genes were observed in vaccinated birds (p < 0.05) in general, with less prevalence in birds fed CP, BP, and CP + BP than NC and BAC (p < 0.05). More than 75 antimicrobial resistance genes (ARGs) detected by the shotgun metagenomics sequencing were impacted by vaccination. Ceca from birds fed CP, BP, and CP + BP showed the lowest (p < 0.05) abundances of ARGs related to multi-drug efflux pumps, modifying/hydrolyzing enzyme and target-mediated mutation, when compared to ceca from birds fed BAC. Targeted metagenomics showed that resistome from BP treatment was distant to other groups for antimicrobials, such as aminoglycosides (p < 0.05). Significant differences in the richness were observed between the vaccinated and non-vaccinated groups for aminoglycosides, ß-lactams, lincosamides, and trimethoprim resistance genes (p < 0.05). Overall, this study demonstrated that dietary berry pomaces and coccidiosis vaccination significantly impacted cecal microbiota, virulome, resistome, and metabolic pathways in broiler chickens.

Growth performance, organ weight, and plasma metabolites in broiler chickens fed corn-soybean meal diet containing berry pomaces and fed without or with multienzymes supplement.

This study evaluated effects of feeding low-bush wild blueberry (LBP) and organic American cranberry (CRP) pomaces without or with multienzyme supplement (ENZ) on growth performance, organ weight and plasma metabolites in broiler chickens. Nonenzyme-fed (no-ENZ: n = 1,575) and enzyme-fed (ENZ: n = 1,575) day-old male Cobb500 broilers were placed in floor pens (45 chicks/pen) and allocated to five corn-soybean meal-based diets: a basal diet supplemented with either bacitracin methylene disalicylate (BMD, 55 mg/kg), 0.5 or 1% of CRP or LBP in a 2 × 5 factorial design for 35-day experiment. Body weight (BW), feed intake (FI) and mortality were recorded whereas BW gain (BWG) and feed conversion ratio (FCR) were calculated. Birds were sampled at days 21 and 35 for organ weights and plasma metabolites. There were no interactions between diet and ENZ on any parameter (P > 0.05) and no effect of ENZ on overall (d 0-35) growth performance and organ weights (P > 0.05). Birds fed BMD were heavier (P < 0.05) at d 35 and had better overall FCR than berry-supplemented birds. Birds fed 1% LBP had poor FCR than birds fed 0.5% CRP. Birds fed LBP exhibited heavier liver (P < 0.05) than birds fed BMD or 1% CRP. The highest plasma concentrations of aspartate transaminase (AST), creatine kinase (CK) at d 28 and gamma-glutamyl transferase (GGT) at d 35 were found in ENZ-fed birds (P < 0.05). At d 28, birds fed 0.5% LBP showed higher plasma AST and CK concentrations (P < 0.05). However, CRP feeding resulted in a lower plasma CK level compared with BMD feeding (P < 0.05). The lowest cholesterol level was detected in 1% CRP-fed birds. In conclusion, this study showed no ENZ effects to potentiate berry pomaces on the overall growth performance of broilers (P < 0.05. However, plasma profiles revealed the potential of ENZ to modulate the metabolism of pomace-fed broilers. LBP increased BW during the starter phase, while CRP increased BW during the grower phase.

Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.

BACKGROUND: Previous population health studies examining adults with acute myeloid leukemia (AML); however many of these, such as the Cancer Genome Atlas, are derived from databases collected by large urban centers. Due to its unique industry and environmental exposures, we hypothesized the West Virginia Appalachian population may have different mutational trends and clinical outcomes. AIMS: To address the concern of under-representation of rural minorities in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML in rural Appalachia. METHODS & RESULTS: Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. A total of 26 patients were identified and whole exome sequencing was performed. Median age was 68 years old. Twenty-one patients had de novo AML (84%). As per European LeukemiaNet (ELN) criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant. The median progression-free survival and overall survival were 16.5 months and 26.6 months, respectively. We noted an increased tumor mutation burden and a higher frequency of specific known driver mutations when compared to The Cancer Genome Atlas database; we also found novel mutations in MUC3A, MUC5AC, HCAR3, ORT2B, and PABPC. Survival outcomes were slightly lower than national average and BCOR mutation correlated with inferior outcomes. CONCLUSION: Our findings provide novel insight into detrimental mutations in AML in a rural, underrepresented population. We discovered several novel mutations and higher frequency of some known driver mutations, which will help us identify therapeutic targets to improve patient outcomes.

Evaluation of the Pharmacokinetic Interaction Between Letermovir and Tacrolimus in Allogeneic Hematopoietic Cell Transplantation Recipients.

Data describing the magnitude of the pharmacokinetic interaction between letermovir and tacrolimus in allogeneic hematopoietic cell transplantation (allo-HCT) recipients are limited, and varying outcomes have been reported. The need for empiric dose adjustment of tacrolimus on initiation of letermovir has not been established; instead, guidelines suggest closely monitoring the tacrolimus trough concentration and adjusting the dose as needed. A better understanding of this interaction is imperative to accurately manage the narrow therapeutic window of tacrolimus post-transplantation. The primary objective of this study was to determine the percent change in tacrolimus concentration-to-dose ratio over the 14-day period after initiation of letermovir. Secondary objectives were to describe the frequency of tacrolimus dose adjustments after initiation of letermovir, the percent change in daily tacrolimus dose over the 14-day period after initiation of letermovir, and the incidence of both subtherapeutic and supratherapeutic tacrolimus trough concentrations. This retrospective chart review included adult allo-HCT recipients at our institution who received tacrolimus in combination with oral letermovir and had been taking tacrolimus for at least 5 days before letermovir initiation. Patients receiving strong CYP3A4 inhibitors or i.v. tacrolimus were excluded. Thirty-five patients were included in the analysis. The median percent increase in tacrolimus concentration-to-dose ratio over the 14-day period after initiation of letermovir was 22% on days 2 to 4, 47% on days 5 to 7, 66% on days 8 to 11, and 81% on days 12 to 14. The mean frequency of tacrolimus dose adjustments was 0.66 on days 2 to 4, 0.69 on days 5 to 7, 1.06 on days 8 to 11, and 0.57 on days 12 to 14. The results of this study show that the pharmacokinetic interaction between tacrolimus and letermovir is substantial and continues to affect tacrolimus concentration over the 14-day period after letermovir initiation. Close monitoring of tacrolimus trough concentration on initiation of letermovir should be considered.

The Northwestern University Novel Urology Residency Curriculum: Updated Outcomes from a 13-Year Experience with Flexible Residency Training and Electives.

INTRODUCTION: We evaluated educational outcomes and satisfaction following institution of a novel, flexible and urology-driven resident curriculum. METHODS: A new urology resident curriculum was instituted at Northwestern University in 2006. Rotation schedules and resident electives were recorded annually. Operative case logs and American Urological Association In-Service Examination scores were collected prospectively. Residents and faculty rated satisfaction with the residency program on a 5-point Likert scale from "poor" to "outstanding." Differences in cases logged, In-Service Examination scores and satisfaction ratings under the new and prior curricula were compared. RESULTS: Curriculum changes included full 5-year urology oversight of the residency curriculum by the program director, 8 months of urology rotations in the first postgraduate year and 2 months of general surgery during the second postgraduate year. General surgery rotations were modified annually based on educational rationale and feedback. Cases logged per resident and In-Service Examination scores were comparable between old and new curricula groups. All residents matriculating under the new curriculum took and passed their written boards. The percentage of faculty and residents describing the program as "outstanding" increased from 50% in 2004‒2005 to 82% in 2017‒2018. Program satisfaction increased significantly when comparing the first and last 6 years (percent rating "outstanding": 56.1±2.1% vs 71.6±10.0%, p=0.028). CONCLUSIONS: After 13 years with the novel curriculum, resident case numbers and In-Service Examination scores remained similar while faculty/resident satisfaction increased. Direct control of general surgery rotations enabled adjustments based on educational rationale. These results demonstrate that a urology-directed and flexible residency program can be instituted without compromising learner outcomes.

Neuroprotective and anxiolytic potential of green rooibos (Aspalathus linearis) polyphenolic extract.

South African rooibos (Aspalathus linearis) tea is globally consumed for its health benefits and caffeine free nature, but no information is available on the neuroprotective capacity of (unfermented) green rooibos. Our aim was to investigate the cytoprotective activity of green rooibos in neuronal cells, including probing antioxidant and enzyme inhibitory properties that could explain observed effects in these cells. We also investigated the anxiolytic potential of green rooibos using zebrafish larval models. Green rooibos extract (Green oxithin™) was assessed for its neuroprotective potential in Neuro-2a cells treated with different concentrations of the extract (12.5-25-50-100 µg mL-1) and different concentrations of hydrogen peroxide (250 or 125 µM) as oxidizing agent. Cell viability (MTT) and redox status (intracellular ROS) were also quantified in these cells. Antioxidant properties of the extract were quantified using cell-free systems (DPPH, ORAC and xanthine/xanthine oxidase), and potential neuroprotection evaluated in terms of its potential to inhibit key enzymes of the CNS (monoamine oxidase A (MOA-A), acetylcholinesterase (AChE) and tyrosinase (TYR)). Results demonstrated that green rooibos extract exerted significant cytoprotective properties in Neuro-2a cells, particularly when exposed to lethal 250 µM hydrogen peroxide, increasing cell survival by more than 100%. This may be ascribed (at least partially) to its capacity to limit intracellular ROS accumulation in these cells. Data from cell-free systems confirmed that green rooibos was able to scavenge free radicals (synthetic and physiological) in a dose dependent manner with a similar profile activity to vitamins C and E. Green rooibos also acted as a moderate MAO-A inhibitor, but had no significant effect on AChE or TYR. Finally, zebrafish larvae treated with lower doses of green rooibos demonstrated a significant anxiolytic effect in the light-dark anxiety model. Using the PTZ excitotoxicity model, green rooibos was shown to rescue GABA receptor signalling, which together with its demonstrated inhibition of MAO-A, may account for the anxiolytic outcome. Current data confirms that green rooibos could be considered a "functional brain food" and may be a good option as starting ingredient in the development of new nutraceuticals.

Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. OBJECTIVE: This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. METHODS: A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality. RESULTS: Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts. CONCLUSIONS: Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Effects of Vaccination Against Coccidiosis on Gut Microbiota and Immunity in Broiler Fed Bacitracin and Berry Pomace.

Feeding practices have been found to influence gut microbiota which play a major role in immunity of poultry. In the present study, changes in cecal microbiota and humoral responses resulting in the 55 ppm bacitracin (BACI), 1% each of cranberry (CP1) and wild blueberry (BP1) pomace alone or in combination (CP+BP) feeding in broiler Cobb 500 vaccinated or not against coccidiosis were investigated. In the non-vaccinated group, no significant treatment effects were observed on performance parameters. Vaccination significantly affected bird's performance parameters particularly during the growing phase from 10 to 20 days of age. In general, the prevalence of coccidiosis and necrotic enteritis (NE) was reduced by vaccination (P < 0.05). BACI-treated birds showed low intestinal lesion scores, and both CP1 and BP1 feed supplementations reduced Eimeria acervulina and Clostridium perfringens incidences similar to BACI. Vaccination induced change in serum enzymes, minerals, and lipid levels in 21-day old birds while, levels of triglyceride (TRIG) and non-esterified fatty acids (NEFA) were higher (P < 0.05) in CP1 treated non-vaccinated group than in the control. The levels of NEFA were lower in BACI- and CP1-fed birds than in the control in non-vaccinated day 28 old birds. The highest levels of all estimated three immunoglobulins (IgY, IgM, and IgA) were found in the vaccinated birds. Metagenomics analysis of the cecal bacterial community in 21-day old birds showed the presence of Firmicutes (90%), Proteobacteria (5%), Actinobacteria (2%), and Bacteroidetes (2%). In the vaccinated group, an effect of BACI was noted on Proteobacteria (P = 0.03). Vaccination and/or dietary treatments influenced the population of Lactobacillaceae, Enterobacteriaceae, Clostridiaceae, and Streptococcaceae which were among the most abundant families. Overall, this study revealed that besides their beneficial effects on performance, alike bacitracin, berry pomaces in poultry feed have profound impacts on the chicken cecal microbiota and blood metabolites that could be influenced by vaccination against coccidiosis.

Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients.

A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200 mg/m2) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.

Organic cranberry pomace and its ethanolic extractives as feed supplement in broiler: impacts on serum Ig titers, liver and bursal immunity.

With the pressure to reduce antibiotics use in poultry production, cost-effective alternative products need to be developed to enhance the bird's immunity. The present study evaluated the efficacy of cranberry fruit by-products to modulate immunity in broiler chickens. Broiler Cobb 500 chicks were fed a control basal diet, basal diet supplemented with bacitracin (BACI, 55 ppm), cranberry pomace at 1% and 2% (CP2), or cranberry pomace ethanolic extract at 150 and 300 ppm (COH300) for 30 d. Blood sera were analyzed at days 21 and 28 of age for Ig levels by ELISA. The innate and adaptive immune-related gene expression levels in the liver and bursa of Fabricius were investigated at 21 d of age by quantitative polymerase chain reaction arrays. At day 21, the highest IgY level was found in the blood serum of the CP2-fed birds. In the liver, 13 of the 22 differentially expressed genes were downregulated across all treatments compared with the control. Expression of genes belonging to innate immunity such as caspase 1 apoptosis-related cysteine peptidase, chemokine receptor 5, interferon gamma, myeloid differentiation primary response gene 88, and Toll-like receptor 3 were significantly downregulated mainly in BACI- and COH300-fed birds. In the bursa, 5 of 9 genes associated with the innate immunity were differentially expressed. The expression of anti-inflammatory IL-10 gene was upregulated in all treatment groups in bursa compared with the control. The expression of transferrin gene was significantly upregulated in livers of birds fed COH300 and in bursa of birds fed BACI, indicating feeding practices and organ-dependant modulation of this gene in broiler. Overall results of this study showed that cranberry product feed supplementation modulated the innate immune and suppressed proinflammatory cytokines in broilers, providing a platform for future investigations to develop berry products in poultry feeding.

Research Note: Effects of supplementing cranberry and blueberry pomaces on meat quality and antioxidative capacity in broilers.

Cranberry and blueberry pomaces are rich in antimicrobial and antioxidant compounds. They have been identified as potential antibiotic alternatives in animal feed, but their antioxidative capacity for maintaining or improving the meat quality in broilers is not well documented. This study was to determine whether cranberry and wild blueberry pomaces in diets could positively influence the broiler meat quality. A total of 3,150 broilers were randomly allotted to 10 dietary treatments with bacitracin methylene disalicylate, wild cranberry pomace (CRP) (0.5 and 1% of the basal diet), and wild blueberry pomace (BLP) (0.5 and 1% of the basal diet) alone or in combination with a mixture of feed enzymes. The results showed that supplementation with the CRP or BLP did not affect meat lightness and yellowness, while the deeper red meat (higher a∗ values) was observed in the birds receiving the diet containing 0.5% BLP against those in CRP treatments (P = 0.015). In addition, inclusion of CRP or BLP in the diet did not change meat texture and proximate composition (moisture, protein, fat, ash) irrespective of pomace concentrations. Although there were no obvious effects of CRP or BLP supplementation on meat antioxidant capacity and the incidence of myopathies (P > 0.05), the upward trend of antioxidant capacity and less severity of woody breast were observed in birds fed with 0.5% CRP. Furthermore, supplementation of 0.5 or 1.0% CRP without the enzyme resulted in higher mRNA levers of Nrf, Gpx2, and HO-1 (P < 0.05). Taken together, 0.5% CRP supplementation without the enzyme could potentially maintain meat quality and attenuate the severity of woody breast.

Gut Microbiota, Blood Metabolites, and Spleen Immunity in Broiler Chickens Fed Berry Pomaces and Phenolic-Enriched Extractives.

This study evaluated the performance, gut microbiota, and blood metabolites in broiler chickens fed cranberry and blueberry products for 30 days. A total of 2,800 male day-old broiler Cobb-500 chicks were randomly distributed between 10 diets: control basal diet; basal diet with bacitracin (BACI); four basal diets with 1 and 2% of cranberry (CP1, CP2) and blueberry (BP1, BP2) pomaces; and four basal diets supplemented with ethanolic extracts of cranberry (COH150, COH300) or blueberry (BOH150, BOH300) pomaces. All groups were composed of seven replicates (40 birds per replicate). Cecal and cloacal samples were collected for bacterial counts and 16S rRNA gene sequencing. Blood samples and spleens were analyzed for blood metabolites and gene expressions, respectively. The supplementation of COH300 and BOH300 significantly increased the body weight (BW) during the starting and growing phases, respectively, while COH150 improved (P < 0.05) the overall cumulated feed efficiency (FE) compared to control. The lowest prevalence (P = 0.01) of necrotic enteritis was observed with CP1 and BP1 compared to BACI and control. Cranberry pomace significantly increased the quinic acid level in blood plasma compared to other treatments. At days 21 and 28 of age, the lowest (P < 0.05) levels of triglyceride and alanine aminotransferase were observed in cranberry pomace and blueberry product-fed birds, respectively suggesting that berry feeding influenced the lipid metabolism and serum enzyme levels. The highest relative abundance of Lactobacillaceae was found in ceca of birds fed CP2 (P < 0.05). In the cloaca, BOH300 significantly (P < 0.005) increased the abundances of Acidobacteria and Lactobacillaceae. Actinobacteria showed a significant (P < 0.05) negative correlation with feed intake (FI) and FE in COH300-treated birds, whereas Proteobacteria positively correlated with the BW but negatively correlated with FI and FE, during the growing phase. In the spleen, cranberry products did not induce the release of any pro-inflammatory cytokines but upregulated the expression of several genes (IL4, IL5, CSF2, and HMBS) involved in adaptive immune responses in broilers. This study demonstrated that feed supplementation with berry products could promote the intestinal health by modulating the dynamics of the gut microbiota while influencing the metabolism in broilers.

Corrigendum: Gut Microbiota, Blood Metabolites, and Spleen Immunity in Broiler Chickens Fed Berry Pomaces and Phenolic-Enriched Extractives.

[This corrects the article DOI: 10.3389/fvets.2020.00150.].

Prospective assessment of Clostridioides (formerly Clostridium) difficile colonization and acquisition in hematopoietic stem cell transplant patients.

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of Clostridium difficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population. METHODS: The primary objectives of this study were to identify the rate of C difficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient. RESULTS: Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of C difficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission. Twelve percent of patients developed CDI that was diagnosed clinically. Univariate analysis showed an increased risk of colonization for patients with three or more prior chemotherapy cycles. CONCLUSIONS: Given high colonization rates coupled with high risk of CDI in this population, providers must be judicious when testing for CDI and interpreting test results for HSCT patients.

D-galactose: a model of accelerated ageing sufficiently sensitive to reflect preventative efficacy of an antioxidant treatment.

Considering that the phenomenon of accelerated ageing contributes to early onset of various chronic diseases, modelling of the relevant dysregulated systems or responses is vital for research aimed at identification of potential therapeutic targets. Here, we aimed to establish a model capable of simulating the redox and inflammatory changes of accelerated ageing-specifically, the aim was early phase accelerated ageing, which would allow therapeutic intervention in a preventative approach prior to clinical disease manifestation. A secondary aim was to evaluate the sensitivity of the model to reflect preventative treatment efficacy. Daily D-galactose injections (250 mg/kg body mass/day) for 8 weeks in 9-week-old male Wistar rats induced a model of early accelerated ageing (decreased plasma FRAP; P < 0.05 and altered inflammatory signalling) and an aged profile in lymph node ultrastructure, but did not yet result in telomere shortening. Preventative daily oral antioxidant administration (grape seed-derived polyphenol, 100 mg/kg body mass) prevented tissue ageing, beneficially modulated the inflammatory response, including neutrophil chemokinetic capacity, and tended to increase absolute telomere length. Data suggests that using a mild model of D-galactose administration than those employed to induce neurodegeneration, simulated the point where oxidative stress starts to overwhelm the endogenous antioxidant response and where a pro-inflammatory phenotype switch manifests. Furthermore, despite the expected small effect size, the model was sufficiently sensitive to reflect benefits of preventative antioxidant treatment in the context of ageing. This model presents a practical model for use in drug discovery, particularly in the context of preventative medicine aimed at limiting oxidative stress-associated ageing. Since this starting point of accelerated ageing as illustrated by current data, is not expected to reflect major ageing-associated changes yet, we recommend that future preventative drug discovery studies employ a longitudinal study design in order to clearly demonstrate the delay of this starting point by preventative strategies.