Evaluating the impact of gypsum as a novel bedding material on broiler performance, foot pad health, and fear response.

Flue Gas Desulfurization (FGD) gypsum is a byproduct of the coal-fired power plant process commonly used to remove sulfur dioxide emissions from the flue gas. FGD gypsum has numerous industrial, agricultural, and environmental applications. This study aimed to explore a novel approach involving the use of FGD gypsum combined with different litter treatments as bedding for broiler production. It focused on performance metrics, including adjusted feed conversion ratio (AFCR) and average body weight (BW), foot pad dermatitis (FPD), and fear response over 5 consecutive flocks. A total of 1,800 one-day-old Ross 708 chicks were randomly assigned to 24 pens (75 birds/pen), divided into 6 treatment groups (4 pens/treatment), with 5 replications and raised until 42 d old (d). Treatments were gypsum that was decaked (D), rotovated (E), and rotovated then windrowed (F) between flocks. Control treatments using pine shavings were decaked (A), rotovated (B), and windrowed postrotovating (C). AFCR, average BW, and mortality were used as a measure of production. Foot pad dermatitis scores were taken on d42 using a scale of 0 (absence), 1 (mild), and 2 (severe). Response to observer and human approach test were used to measure fear response. Data were analyzed as a 2-way ANOVA (Proc Glimmix) for the main effects of bedding type and litter treatment. Means were identified using Tukey's HSD. No effect of bedding type or litter treatment was found for AFCR, BW, or mortality. FPD scores 2 and 1, were higher with pine shavings than gypsum (P = 0.01 and P = 0.01, respectively). While FPD scores 0 were higher for gypsum than the pine shaving (P = 0.01). No difference in fear response was found among birds raised on any of the gypsum litter treatments and any of the pine shaving litter treatments. Overall, the use of gypsum as bedding results in equivalent production and fear response to pine shavings, while increasing FPD quality when compared to pine shaving.

Meat quality of broiler chickens processed using electrical and controlled atmosphere stunning systems.

Increased consumer concern for animal welfare has led some poultry producers to alter their stunning methods from electrical to controlled atmosphere stunning. The potential for different impacts on meat quality between commercially applied controlled atmosphere stunning (CAS) and electrical stunning (ES) using current US parameters needs further evaluation. Three trials were conducted in a commercial broiler processing facility that uses separate processing lines for ES and CAS. Blood glucose concentrations were measured from broilers stunned by either CAS or ES at: 1) lairage, 2) pre-stunning, and 3) post-stunning, using a glucose monitor. Occurrence of visible wing damage was evaluated post-defeathering and breast fillet meat quality was evaluated through measurement of pH, color, and drip loss at deboning and after 24 h. Data were analyzed using GLM or chi-square with a significance at P ≤ 0.05 and means were separated by Tukey's HSD. Blood glucose concentrations (mg/dL) from CAS and ES birds were not different at lairage (284, 272, P = 0.2646) or immediately prior to stunning (274, 283, P = 0.6425). Following stunning and neck cut, circulating blood glucose from birds stunned by CAS was higher than ES (418, 259, P < 0.0001). CAS carcasses had more visible wing damage than ES carcasses (3.6%, 2.2%, P < 0.0001). Breast fillet pH was lower, L* was higher, and a* was lower at debone for CAS fillets (5.81, 54.65, 1.96) compared to ES fillets (5.92, 53.15, 2.31, P < 0.0001, P = 0.0005, P = 0.0303). Drip loss did not differ between breast fillets from CAS or ES broilers (4.83, 4.84; P = 0.0859). The implications of increased blood glucose concentration post-CAS are unknown and require further evaluation. However, the increase in visible wing damage observed post-defeathering from CAS carcasses indicated a need for equipment parameter adjustments during the process from stunning through defeathering when using CAS for broiler stunning. Although differences were observed in breast fillet attributes at deboning, these differences would have minimal practical application and were no longer present at 24 h. Overall, use of CAS in a commercial facility resulted in differences in subsequent product quality when compared to ES.

Data curation to support toxicity assessments using the Integrated Chemical Environment.

Humans are exposed to large numbers of chemicals during their daily activities. To assess and understand potential health impacts of chemical exposure, investigators and regulators need access to reliable toxicity data. In particular, reliable toxicity data for a wide range of chemistries are needed to support development of new approach methodologies (NAMs) such as computational models, which offer increased throughput relative to traditional approaches and reduce or replace animal use. NAMs development and evaluation require chemically diverse data sets that are typically constructed by incorporating results from multiple studies into a single, integrated view; however, integrating data is not always a straightforward task. Primary study sources often vary in the way data are organized and reported. Metadata and information needed to support interoperability and provide context are often lacking, which necessitates literature research on the assay prior to attempting data integration. The Integrated Chemical Environment (ICE) was developed to support the development, evaluation, and application of NAMs. ICE provides curated toxicity data and computational tools to integrate and explore available information, thus facilitating knowledge discovery and interoperability. This paper describes the data curation workflow for integrating data into ICE. Data destined for ICE undergo rigorous harmonization, standardization, and formatting processes using both automated and manual expert-driven approaches. These processes improve the utility of the data for diverse analyses and facilitate application within ICE or a user's external workflow while preserving data integrity and context. ICE data curation provides the structure, reliability, and accessibility needed for data to support chemical assessments.

Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues.

BACKGROUND: The developmental toxicity potential (dTP) concentration from the devTOX quickPredict (devTOXqP ) assay, a metabolomics-based human induced pluripotent stem cell assay, predicts a chemical's developmental toxicity potency. Here, in vitro to in vivo extrapolation (IVIVE) approaches were applied to address whether the devTOXqP assay could quantitatively predict in vivo developmental toxicity lowest effect levels (LELs) for the prototypical teratogen valproic acid (VPA) and a group of structural analogues. METHODS: VPA and a series of structural analogues were tested with the devTOXqP assay to determine dTP concentration and we estimated the equivalent administered doses (EADs) that would lead to plasma concentrations equivalent to the in vitro dTP concentrations. The EADs were compared to the LELs in rat developmental toxicity studies, human clinical doses, and EADs reported using other in vitro assays. To evaluate the impact of different pharmacokinetic (PK) models on IVIVE outcomes, we compared EADs predicted using various open-source and commercially available PK and physiologically based PK (PBPK) models. To evaluate the effect of in vitro kinetics, an equilibrium distribution model was applied to translate dTP concentrations to free medium concentrations before subsequent IVIVE analyses. RESULTS: The EAD estimates for the VPA analogues based on different PK/PBPK models were quantitatively similar to in vivo data from both rats and humans, where available, and the derived rank order of the chemicals was consistent with observed in vivo developmental toxicity. Different models were identified that provided accurate predictions for rat prenatal LELs and conservative estimates of human safe exposure. The impact of in vitro kinetics on EAD estimates is chemical-dependent. EADs from this study were within range of predicted doses from other in vitro and model organism data. CONCLUSIONS: This study highlights the importance of pharmacokinetic considerations when using in vitro assays and demonstrates the utility of the devTOXqP human stem cell-based platform to quantitatively assess a chemical's developmental toxicity potency.

Evaluation of intravenous T-61 as a euthanasia method for birds.

The use of T-61 as a sole euthanasia agent for birds was investigated. Nine broiler chickens (Gallus gallus domesticus) were euthanized by intravenous T-61 and assessed for insensibility [brainstem reflexes: nictitating membrane reflex (NIC), palpebral blink reflex (PAL)], brain death [isoelectric electroencephalogram activity (EEG)], cessation of audible heartbeat, and abnormal electrocardiogram. Birds were considered dead when the heart rate was less than 180 beats/minute with an isoelectric EEG. No vocalization or wing flapping occurred. Both NIC and PAL were lost 10.5 s from start of injection and audible heartbeat ceased at 24.5 s. Latency to isoelectric activity was 16.6 s. All but 1 bird died within 60 s. Rapid induction of insensibility meant birds did not experience pain and distress within 10.5 s from start of injection and birds were not conscious during cardiac and circulatory arrest. Intravenous injection of T-61 is an effective and efficient euthanasia method for birds.

Évaluation du T-61 intraveineux comme méthode d'euthanasie pour les espèces aviaires. La présente étude visait à évaluer l'utilisation du T-61 comme seul agent d'euthanasie pour les oiseaux. Neuf poulets de chair (Gallus gallus domesticus) ont été euthanasiés par injection intraveineuse de T-61 et évalués pour leur insensibilité [réflexes du tronc cérébral : réflexe de la membrane nictitante (NIC) et réflexe palpébral (PAL)], mort cérébrale [activité isoélectrique de l'électroencéphalogramme (EEG)], arrêt du rythme cardiaque audible et électrocardiogramme (ECG) anormal. Les oiseaux étaient considérés comme morts lorsque la fréquence cardiaque (ECG) était inférieure à 180 battements par minute avec un EEG isoélectrique. Aucune vocalisation ou battement d'aile ne s'est produit. Les réflexes NIC et PAL ont été perdus 10,5 s après l'injection et le rythme cardiaque audible a cessé à 24,5 s. La latence jusqu'à l'activité isoélectrique était de 16,6 s. Tous les oiseaux sauf un sont morts dans les 60 s. L'induction rapide de l'insensibilité signifiait que les oiseaux étaient incapables de ressentir de la douleur et de la détresse dans les 10,5 secondes suivant l'injection et que les oiseaux n'étaient pas conscients pendant un arrêt cardiaque et circulatoire. L'injection intraveineuse de T-61 est une méthode d'euthanasie efficace et efficiente pour les oiseaux.(Traduit par Dr Serge Messier).

An integrated chemical environment with tools for chemical safety testing.

Moving toward species-relevant chemical safety assessments and away from animal testing requires access to reliable data to develop and build confidence in new approaches. The Integrated Chemical Environment (ICE) provides tools and curated data centered around chemical safety assessment. This article describes updates to ICE, including improved accessibility and interpretability of in vitro data via mechanistic target mapping and enhanced interactive tools for in vitro to in vivo extrapolation (IVIVE). Mapping of in vitro assay targets to toxicity endpoints of regulatory importance uses literature-based mode-of-action information and controlled terminology from existing knowledge organization systems to support data interoperability with external resources. The most recent ICE update includes Tox21 high-throughput screening data curated using analytical chemistry data and assay-specific parameters to eliminate potential artifacts or unreliable activity. Also included are physicochemical/ADME parameters for over 800,000 chemicals predicted by quantitative structure-activity relationship models. These parameters are used by the new ICE IVIVE tool in combination with the U.S. Environmental Protection Agency's httk R package to estimate in vivo exposures corresponding to in vitro bioactivity concentrations from stored or user-defined assay data. These new ICE features allow users to explore the applications of an expanded data space and facilitate building confidence in non-animal approaches.

Binding of peanut allergen Ara h 2 with Vaccinium fruit polyphenols.

The potential for 42 different polyphenols found in Vaccinium fruits to bind to peanut allergen Ara h 2 and inhibit IgE binding epitopes was investigated using cheminformatics techniques. Out of 12 predicted binders, delphinidin-3-glucoside, cyanidin-3-glucoside, procyanidin C1, and chlorogenic acid were further evaluated in vitro. Circular dichroism, UV-Vis spectroscopy, and immunoblotting determined their capacity to (i) bind to Ara h 2, (ii) induce protein secondary structural changes, and (iii) inhibit IgE binding epitopes. UV-Vis spectroscopy clearly indicated that procyanidin C1 and chlorogenic acid interacted with Ara h 2, and circular dichroism results suggested that interactions with these polyphenols resulted in changes to Ara h 2 secondary structures. Immunoblotting showed that procyanidin C1 and chlorogenic acid bound to Ara h 2 significantly decreased the IgE binding capacity by 37% and 50%, respectively. These results suggest that certain polyphenols can inhibit IgE recognition of Ara h 2 by obstructing linear IgE epitopes.

Clinical course outcomes for store and forward teledermatology versus conventional consultation: a randomized trial.

We assessed the clinical course of patients after store and forward teledermatology in comparison with conventional consultations. Patients being referred from primary care to dermatology clinics were randomly assigned to teledermatology or a conventional consultation. A total of 392 patients were randomized; 261 patients completed the study and were included in the analysis. Their clinical course was rated on a five-point scale by a panel of three dermatologists, blinded to study assignment, who reviewed serial digital image sets. The clinical course was assessed by comparing images sets between baseline and first clinic visit (if one occurred) and between baseline and nine months. There was no evidence to suggest a difference between the two groups in either clinical course between baseline and nine months post-referral (P = 0.88) or between baseline and the first dermatology clinic visit (P = 0.65). Among teledermatology referrals, subsequent presentation for an in-person dermatology clinic visit was significantly correlated with clinical course (P = 0.023). Store and forward teledermatology did not result in a significant difference in clinical course at either of two post-referral time periods.

Effect of store and forward teledermatology on quality of life: a randomized controlled trial.

IMPORTANCE: Although research on quality of life and dermatologic conditions is well represented in the literature, information on teledermatology's effect on quality of life is virtually absent. OBJECTIVE: To determine the effect of store and forward teledermatology on quality of life. DESIGN: Two-site, parallel-group, superiority randomized controlled trial. SETTING: Dermatology clinics and affiliated sites of primary care at 2 US Department of Veterans Affairs medical facilities. PARTICIPANTS: Patients being referred to a dermatology clinic were randomly assigned, stratified by site, to teledermatology or the conventional consultation process. Among the 392 patients who met the inclusion criteria and were randomized, 326 completed the allocated intervention and were included in the analysis. INTERVENTIONS: Store and forward teledermatology (digital images and a standardized history) or conventional text-based consultation processes were used to manage the dermatology consultations. Patients were followed up for 9 months. MAIN OUTCOME MEASURES: The primary end point was change in Skindex-16 scores, a skin-specific quality-of-life instrument, between baseline and 9 months. A secondary end point was change in Skindex-16 scores between baseline and 3 months. RESULTS: Patients in both randomization groups demonstrated a clinically significant improvement in Skindex-16 scores between baseline and 9 months with no significant difference by randomization group (P = .66, composite score). No significant difference in Skindex-16 scores by randomization group between baseline and 3 months was found (P = .39, composite score). CONCLUSIONS: Compared with the conventional consultation process, store and forward teledermatology did not result in a statistically significant difference in skin-related quality of life at 3 or 9 months after referral. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00488293.

Impact of global health residency training on medical knowledge of immigrant health.

Lack of global health knowledge places immigrants at risk of iatrogenic morbidity. Although global health education programs have grown in popularity, measurable impact is lacking. We previously surveyed 363 physicians in training across 15 programs in four countries in 2004 regarding basic parasite knowledge and recognition of Strongyloides risk through a theoretical case scenario. In 2005, the University of Minnesota implemented a formal global health training program (GHP). In 2009, the identical survey was repeated. Strongyloidiasis recognition increased from 11.1% (19/171) in 2004 to 39.4% (50/127) in 2009 (P < 0.001). Trainees participating in formal didactic and interactive curriculum had superior recognition (77% versus 29%; P < 0.001). In a multivariate model of GHP training activities, participation in an American Society of Tropical Medicine and Hygiene-accredited global health certificate course increased recognition (odds ratio = 9.5, 95% confidence interval = 2.5-36, P = 0.001), whereas participation in international electives alone did not (P = 0.9). A formal GHP curriculum was associated with improved knowledge regarding common parasitic infections and the risk of iatrogenic morbidity and mortality due to strongyloidiasis.

Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings.

BACKGROUND: Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Subclinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART). We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with subclinical cryptococcosis and the efficacy of preemptive fluconazole therapy. METHODS: There were 609 ART-naive adults with AIDS who started ART in Kampala, Uganda, and who had a serum CRAG prospectively measured during 2004-2006. The number needed to test and treat with a positive CRAG was assessed for > or = 30-month outcomes. RESULTS: In the overall cohort, 50 persons (8.2%) were serum CRAG positive when starting ART. Of 295 people with a CD4(+) cell count < or = 100 cells/microL and without prior CM, 26 (8.8%; 95% confidence interval [CI], 5.8%-12.6%) were CRAG positive, of whom 21 were promptly treated with fluconazole (200-400 mg) for 2-4 weeks. Clinical CM developed in 3 fluconazole-treated persons, and 30-month survival was 71% (95% CI, 48%-89%). In the 5 CRAG-positive persons with a CD4(+) cell count < or = 100 cells/microL treated with ART but not fluconazole, all died within 2 months of ART initiation. The number needed to test and treat with CRAG screening and fluconazole to prevent 1 CM case is 11.3 (95% CI, 7.9-17.1) at costs of $190 (95% CI, $132-$287). The number needed to test and treat to save 1 life is 15.9 (95% CI, 11.1-24.0) at costs of $266 (95% CI, $185-$402). The cost per disability-adjusted life year saved is $21 (95% CI, $15-$32). CONCLUSIONS: Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4(+) cell count < or = 100 cells/microL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.

Role of topical calcineurin inhibitors in the treatment of seborrheic dermatitis: a review of pathophysiology, safety, and efficacy.

Seborrheic dermatitis (SD) is characterized by erythematous pruritic patches and plaques with greasy scale that occur in sebaceous areas. It is common, affecting up to 3% of the population. Past treatments have relied on a wide variety of anti-inflammatory and antifungal agents, but corticosteroids have limited use because of long-term adverse effects. Topical calcineurin inhibitors provide a safe alternative for the treatment of SD, as these drugs block the inflammatory cascade involved in the disease process and pose no risk of skin atrophy. Studies of topical pimecrolimus and tacrolimus in the treatment of SD have found that improvement occurred within 2 weeks, and if SD recurred after stopping treatment, it was significantly less severe. There have been no studies of the comparative efficacy of pimecrolimus versus tacrolimus for the treatment of SD. Common adverse effects of mild burning and irritation have been associated with the use of both of these agents. Safety profile studies are limited to studies of atopic dermatitis, which show no increase in infection rate, photocarcinogenicity, or signs of immunosuppression in patients using topical calcineurin inhibitors for long-term treatment. This article reviews the clinical trials of pimecrolimus and tacrolimus in the treatment of SD, focusing on efficacy and safety.