Meta-Analysis of the Effects of Yeast Cell Wall Extract Supple-Mentation during Mycotoxin Challenges on the Performance of Laying Hens.

A random-effects meta-analysis was conducted to investigate the effect of mycotoxins (MT) without or with the inclusion of yeast cell wall extract (YCWE, Mycosorb®, Alltech, Inc., Nicholasville, KY, USA) on laying hen performance. A total of 25 trials were collected from a literature search, and data were extracted from 8 of these that met inclusion criteria, for a total of 12 treatments and 1774 birds. Laying hens fed MT had lower (p < 0.05) body weight (BW) by -50 g, egg production by -6.3 percentage points, and egg weight by -1.95 g than control fed hens (CTRL). Inclusion of YCWE during the mycotoxin challenges (YCWE + MT) resulted in numerically greater (p = 0.441) BW by 12.5 g, while egg production and egg weight were significantly (p < 0.0001) higher by 4.2 percentage points and 1.37 g, respectively. Furthermore, economic assessment calculations indicated that YCWE may not only support hen performance but also resulted in a positive return on investment. In conclusion, mycotoxins can play a role in negatively impacting laying hen performance and profitability. Inclusion of YCWE in feed with mycotoxin challenges provided benefits to egg production and egg weight and may support profitability. As such, the inclusion of YCWE could play an important role in minimizing mycotoxin effects and in turn aid farm efficiency and profitability.

Use of Yeast Cell Wall Extract for Growing Pigs Consuming Feed Contaminated with Mycotoxins below or above Regulatory Guidelines: A Meta-Analysis with Meta-Regression.

Using a random-effects meta-analysis, the performance of growing pigs under a mycotoxin challenge (MT) with or without supplementation of yeast cell wall extract (YCWE, Mycosorb®, Alltech Inc.) was evaluated. Both MT and YCWE were also compared to animal controls not receiving mycotoxins (CTRL). Meta-regression was used to further explore the impacts of MT at/below (category 1) or above (category 2) global regulatory guidelines. Following the screening, 23 suitable references (30 mycotoxin treatments) were used. Overall, MT lowered average daily gain (ADG, p < 0.001) and average daily feed intake (ADFI, p < 0.0001) from CTRL by -84 and -165 g, respectively. Inclusion of YCWE during mycotoxin challenges (YCWE+MT, average 2.1 kg/ton) tended to result in greater ADG (+17 g, p = 0.068) compared to MT treatments. The gain-to-feed ratio (G:F) was not impacted by MT or YCWE+MT. Further investigation by meta-regression revealed that pigs fed MT in category 1 had lower ADG (-78.5 g, p < 0.001) versus CTRL, while YCWE+MT had higher ADG (+48 g, p < 0.001) over MT and was similar to CTRL. The ADFI was not impacted, although YCWE+MT had ADFI values similar to the CTRL. In category 2, ADG and ADFI of pigs fed MT were lower than CTRL (-85.1 and -166 g, respectively, p < 0.0001), with a tendency for YCWE+MT to result in higher ADFI (+25.3 g, p = 0.062). In summary, the inclusion of YCWE provided benefits to performance during common mycotoxin challenge levels (at or below regulatory guidelines).

Robust and scalable single-molecule protein sequencing with fluorosequencing.

The need to accurately survey proteins and their modifications with ever higher sensitivities, particularly in clinical settings with limited samples, is spurring development of new single molecule proteomics technologies. Fluorosequencing is one such highly parallelized single molecule peptide sequencing platform, based on determining the sequence positions of select amino acid types within peptides to enable their identification and quantification from a reference database. Here, we describe substantial improvements to fluorosequencing, including identifying fluorophores compatible with the sequencing chemistry, mitigating dye-dye interactions through the use of extended polyproline linkers, and developing an end-to-end workflow for sample preparation and sequencing. We demonstrate by fluorosequencing peptides in mixtures and identifying a target neoantigen from a database of decoy MHC peptides, highlighting the potential of the technology for high sensitivity clinical applications.

Plasma proteome of growing tumors.

Early detection of cancer is vital for the best chance of successful treatment, but half of all cancers are diagnosed at an advanced stage. A simple and reliable blood screening test applied routinely would therefore address a major unmet medical need. To gain insight into the value of protein biomarkers in early detection and stratification of cancer we determined the time course of changes in the plasma proteome of mice carrying transplanted human lung, breast, colon, or ovarian tumors. For protein measurements we used an aptamer-based assay which simultaneously measures ~ 5000 proteins. Along with tumor lineage-specific biomarkers, we also found 15 markers shared among all cancer types that included the energy metabolism enzymes glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phophate isomerase and dihydrolipoyl dehydrogenase as well as several important biomarkers for maintaining protein, lipid, nucleotide, or carbohydrate balance such as tryptophanyl t-RNA synthetase and nucleoside diphosphate kinase. Using significantly altered proteins in the tumor bearing mice, we developed models to stratify tumor types and to estimate the minimum detectable tumor volume. Finally, we identified significantly enriched common and unique biological pathways among the eight tumor cell lines tested.

Current Strategies in Medical Management of the Geriatric Hip Fracture Patient.

Orthogeriatric hip fractures have high morbidity and mortality rates. Modern management focuses on multidisciplinary collaboration for prompt surgical stabilization, early mobilization with multimodal pain control to avoid opioid consumption, and an enhanced recovery pathway. Despite these advances, postoperative complications and mortality rates remain higher than age-matched control subjects. The authors of this article represent the orthopaedic, anesthesia, and hospitalist medicine members of a multidisciplinary team at a single, Level 1 trauma center. Our goal was to provide an up-to-date comprehensive review of orthogeriatric hip fracture perioperative management from a multidisciplinary perspective that every orthopaedic surgeon should know.

Meta-analysis of the effects of mycotoxins and yeast cell wall extract supplementation on the performance, livability, and environmental sustainability of broiler production.

The effect of mycotoxins (MT) on broiler performance without or with the inclusion of yeast cell wall extract (YCWE, Mycosorb, Alltech, Inc., KY) was evaluated in a random-effects meta-analysis. Data was extracted from 25 research experiments with a total of 10,307 broilers. Broilers fed MT had lower (P < 0.001) body weight gain (BWG, -217 g), reduced feed intake (FI, -264 g), increased feed conversion ratio (FCR, 0.12), and greater mortality by 2.01%. Inclusion of YCWE improved (P < 0.001) BWG (59 g) and FI (65 g), lowered FCR (-0.05), and reduced mortality by 1.74%. Additionally, change in European Production Efficiency Factor (EPEF) was assessed. Feeding MT lowered (P < 0.001) EPEF while YCWE increased (P < 0.001) EPEF. Finally, the carbon footprint of production was evaluated. Control fed birds produced an estimated 1.93 kg CO2-equivalent/kg liveweight (LW), while MT fed broilers produced 2.13 kg CO2-equivalent/kg LW and YCWE inclusion lowered this to 2.03 kg CO2-equivalent/kg LW which resulted in -25 tonnes less CO2-equivalent output per 100,000 birds with YCWE. In conclusion, mycotoxins can play a role in reducing broiler performance and farm production output, as well as increase the carbon footprint. Inclusion of YCWE in feed under a mycotoxin challenge can improve broiler performance and output, as well as lower carbon footprint, which could play a role in farm efficiency, profitability, and environmental sustainability.

Relationships between Prediction Accuracy, Metacognitive Reflection, and Performance in Introductory Genetics Students.

Cognitive scientists have previously shown that students' perceptions of their learning and performance on assessments often do not match reality. This process of self-assessing performance is a component of metacognition, which also includes the practice of thinking about one's knowledge and identifying and implementing strategies to improve understanding. We used a mixed-methods approach to investigate the relationship between students' perceptions of their performance through grade predictions, their metacognitive reflections after receiving their grades, and their actual performance during a semester-long introductory genetics course. We found that, as a group, students do not display better predictive accuracy nor more metacognitive reflections over the semester. However, those who shift from overpredicting to matching or underpredicting also show improved performance. Higher performers are overall more likely to answer reflection questions than lower-performing peers. Although high-performing students are usually more metacognitive in their reflections, an increase in a student's frequency of metacognitive responses over time does not necessarily predict a grade increase. We illustrate several example trends in student reflections and suggest possible next steps for helping students implement better metacognitive regulation.

A Cross-Sectional Evaluation of Outcomes of Pediatric Thyroglossal Duct Cyst Excision.

INTRODUCTION: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cysts. They may become infected causing dysphagia or respiratory distress. Accordingly, the treatment is always surgical removal. OBJECTIVES: The objectives of this article were to examine complications following TGDC excision by surgical specialty, demographics, and comorbid conditions. METHODS: A retrospective review of the National Surgical Quality Improvement Program database was performed. Pediatric cases from January 1, 2014 to November 1, 2015 with a current procedure terminology code of 60,280 (excision of TGDC or sinus) were included. Statistical analysis was performed to assess associations between complications and surgical specialty, demographics, and comorbidities. RESULTS: Of the 867 cases that met inclusion criteria, the median age was 4 years. There were 448 males (52.3%) and 408 females (47.7%). Thirty-six patients (4.2%) experienced at least one 30-day complication. The most predominant complications were reoperation (19 patients, 2.2%), readmission (18 patients, 2.1%), and surgical site infection (16 patients, 1.9%). There was no statistically significant difference between complications and surgical specialty. In those experiencing a complication, there was a statistically significant difference between males (86.1%) and females (13.9%). Of patients with at least one comorbidity, 36.67% had a complication, while 17.22% did not have a complication. There was also a statistically significant difference in the percentage of patients with a past medical history of asthma between those with at least one complication (16.67%) compared to those without any complications (4.76%). CONCLUSIONS: excision is a generally safe procedure across surgical specialties. There is a higher complication rate in males compared to females as well as those with a history of at least one medical comorbidity and those with asthma. The most common 30-day complications are reoperation, readmission, and surgical site infection.

Multi-tiered analyses of honey bees that resist or succumb to parasitic mites and viruses.

BACKGROUND: Varroa destructor mites, and the numerous viruses they vector to their honey bee hosts, are among the most serious threats to honey bee populations, causing mortality and morbidity to both the individual honey bee and colony, the negative effects of which convey to the pollination services provided by honey bees worldwide. Here we use a combination of targeted assays and deep RNA sequencing to determine host and microbial changes in resistant and susceptible honey bee lineages. We focus on three study sets. The first involves field sampling of sympatric western bees, some derived from resistant stock and some from stock susceptible to mites. The second experiment contrasts three colonies more deeply, two from susceptible stock from the southeastern U.S. and one from mite-resistant bee stock from Eastern Texas. Finally, to decouple the effects of mites from those of the viruses they vector, we experimentally expose honey bees to DWV in the laboratory, measuring viral growth and host responses. RESULTS: We find strong differences between resistant and susceptible bees in terms of both viral loads and bee gene expression. Interestingly, lineages of bees with naturally low levels of the mite-vectored Deformed wing virus, also carried lower levels of viruses not vectored by mites. By mapping gene expression results against current ontologies and other studies, we describe the impacts of mite parasitism, as well as viruses on bee health against two genetic backgrounds. We identify numerous genes and processes seen in other studies of stress and disease in honey bee colonies, alongside novel genes and new patterns of expression. CONCLUSIONS: We provide evidence that honey bees surviving in the face of parasitic mites do so through their abilities to resist the presence of devastating viruses vectored by these mites. In all cases, the most divergence between stocks was seen when bees were exposed to live mites or viruses, suggesting that gene activation, rather than constitutive expression, is key for these interactions. By revealing responses to viral infection and mite parasitism in different lineages, our data identify candidate proteins for the evolution of mite tolerance and virus resistance.

Co-Occurrence of 35 Mycotoxins: A Seven-Year Survey of Corn Grain and Corn Silage in the United States.

Mycotoxins contaminate crops worldwide and play a role in animal health and performance. Multiple mycotoxins may co-occur which may increase the impact on the animal. To assess the multiple mycotoxin profile of corn (Zea mays), we conducted a 7-year survey of new crop corn grain and silage in the United States. A total of 711 grain and 1117 silage samples were collected between 2013 and 2019 and analyzed for the simultaneous presence of 35 mycotoxins using ultra-performance liquid chromatography-tandem mass spectrometry. The measured mean number of mycotoxins per sample were 4.8 (grain) and 5.2 (silage), ranging from 0 to 13. Fusaric acid (FA) was most frequently detected in 78.1 and 93.8% of grains and silages, respectively, followed by deoxynivalenol (DON) in 75.7 and 88.2% of samples. Fumonisin B1 (FB1), fumonisin B2 and 15-acetyl-deoxynivalenol (15ADON) followed. The greatest (p < 0.05) co-occurrence was between FA and DON in 59.1% of grains and 82.7% of silages, followed by FA with FB1, DON with 15ADON, and FA with 15ADON. Although many samples had lower mycotoxin concentrations, 1.6% (grain) and 7.9% (silage) of tested samples had DON ≥ 5000 µg/kg. Fumonisins were detected ≥ 10,000 µg/kg in 9.6 and 3.9% of grain and silage samples, respectively. Concentrations in grain varied by year for eight mycotoxin groups (p < 0.05), while all 10 groups showed yearly variations in silage. Our survey suggest that multiple mycotoxins frequently co-occur in corn grain and silage in the United States, and some of the more prevalent mycotoxins are those that may not be routinely analyzed (i.e., FA and 15ADON). Assessment of multiple mycotoxins should be considered when developing management programs.

Mayday sustains trans-synaptic BMP signaling required for synaptic maintenance with age.

Maintaining synaptic structure and function over time is vital for overall nervous system function and survival. The processes that underly synaptic development are well understood. However, the mechanisms responsible for sustaining synapses throughout the lifespan of an organism are poorly understood. Here, we demonstrate that a previously uncharacterized gene, CG31475, regulates synaptic maintenance in adult Drosophila NMJs. We named CG31475 mayday due to the progressive loss of flight ability and synapse architecture with age. Mayday is functionally homologous to the human protein Cab45, which sorts secretory cargo from the Trans Golgi Network (TGN). We find that Mayday is required to maintain trans-synaptic BMP signaling at adult NMJs in order to sustain proper synaptic structure and function. Finally, we show that mutations in mayday result in the loss of both presynaptic motor neurons as well as postsynaptic muscles, highlighting the importance of maintaining synaptic integrity for cell viability.

Simultaneous cross-evaluation of heterogeneous E. coli datasets via mechanistic simulation.

The extensive heterogeneity of biological data poses challenges to analysis and interpretation. Construction of a large-scale mechanistic model of Escherichia coli enabled us to integrate and cross-evaluate a massive, heterogeneous dataset based on measurements reported by various groups over decades. We identified inconsistencies with functional consequences across the data, including that the total output of the ribosomes and RNA polymerases described by data are not sufficient for a cell to reproduce measured doubling times, that measured metabolic parameters are neither fully compatible with each other nor with overall growth, and that essential proteins are absent during the cell cycle-and the cell is robust to this absence. Finally, considering these data as a whole leads to successful predictions of new experimental outcomes, in this case protein half-lives.

Outcomes of pediatric thyroidectomy: a cross-sectional evaluation.

Introduction: Pediatric thyroidectomy is performed by a variety of surgical specialties. Thyroidectomy can result in a number of complications. Previous studies cite that the most common complications in children are pain and transient hypocalcemia. The purposes of this report are to assess the adverse events of thyroidectomies performed in the pediatric population and to assess the relationship between surgical specialties and postoperative thyroidectomy complications. Methods: We conducted a cross-sectional analysis of cases from January 1, 2014 through November 1, 2015 using the National Surgical Quality Improvement Program database for patients undergoing excision of cyst or adenoma of the thyroid, unilateral thyroid lobectomy, or total thyroidectomy. Results: Of the 344 patients who underwent thyroidectomy, 10 (2.9%) experienced at least one complication. The most common complications were readmission, surgical site infections, and wound disruption. There was a statistically significant association between complication incidence and surgical specialty (p=0.006). Pediatric otolaryngology had a statistically significantly higher number of complications than pediatric surgery (p<0.008). Conclusion: Overall, the incidence of adverse events following pediatric thyroidectomy was low.

Dynamic evolution in the key honey bee pathogen deformed wing virus: Novel insights into virulence and competition using reverse genetics.

The impacts of invertebrate RNA virus population dynamics on virulence and infection outcomes are poorly understood. Deformed wing virus (DWV), the main viral pathogen of honey bees, negatively impacts bee health, which can lead to colony death. Despite previous reports on the reduction of DWV diversity following the arrival of the parasitic mite Varroa destructor, the key DWV vector, we found high genetic diversity of DWV in infested United States honey bee colonies. Phylogenetic analysis showed that divergent US DWV genotypes are of monophyletic origin and were likely generated as a result of diversification after a genetic bottleneck. To investigate the population dynamics of this divergent DWV, we designed a series of novel infectious cDNA clones corresponding to coexisting DWV genotypes, thereby devising a reverse-genetics system for an invertebrate RNA virus quasispecies. Equal replication rates were observed for all clone-derived DWV variants in single infections. Surprisingly, individual clones replicated to the same high levels as their mixtures and even the parental highly diverse natural DWV population, suggesting that complementation between genotypes was not required to replicate to high levels. Mixed clone-derived infections showed a lack of strong competitive exclusion, suggesting that the DWV genotypes were adapted to coexist. Mutational and recombination events were observed across clone progeny, providing new insights into the forces that drive and constrain virus diversification. Accordingly, our results suggest that Varroa influences DWV dynamics by causing an initial selective sweep, which is followed by virus diversification fueled by negative frequency-dependent selection for new genotypes. We suggest that this selection might reflect the ability of rare lineages to evade host defenses, specifically antiviral RNA interference (RNAi). In support of this hypothesis, we show that RNAi induced against one DWV strain is less effective against an alternate strain from the same population.

A cross-sectional evaluation of outcomes of pediatric branchial cleft cyst excision.

OBJECTIVE: To examine complications following pediatric branchial cleft cyst excision by surgical specialty, demographics, and comorbid conditions. METHODS: A retrospective review of the National Surgical Quality Improvement Program database was performed. Pediatric cases from January 1, 2015 through May 1, 2017 with a current procedural terminology code of 42810 (excision branchial cleft cyst or vestige, confined to skin and subcutaneous tissues) or 42815 (excision branchial cleft cyst, vestige, or fistula, extending beneath subcutaneous tissues and/or into the pharynx) were included. Statistical analysis was performed to assess associations between complications and surgical specialty, demographics, and comorbidities. RESULTS: Of the 895 cases that met inclusion criteria, the median age was two years and there was an approximately equal number of males (46.8%) and females (53.2%). Forty-five patients (5.0%) experienced at least one 30-day complication, the most predominant of which was superficial surgical site infection. There was no statistically significant difference between complications and surgical specialty, complications and patient demographics, or complications and depth of excision. There was a statistically significant difference (p = 0.05) in the percentage of patients with a past medical history of developmental delay between those with at least one complication (11.1%) compared to those without any complications (4.2%). CONCLUSION AND RELEVANCE: Branchial cleft excision is a generally safe procedure across surgical specialties and patient demographics. There is an association between a history of developmental delay and 30-day postoperative complications.