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The presence of detrusor muscle is essential for accurate staging of T1 cancers. Detrusor muscle presence can be a quality indicator of transurethral resection of bladder tumor for nonmuscle invasive bladder cancer. We hypothesized that increasing surgeon awareness of personal and institutional detrusor muscle sampling rates could improve resection quality and long-term oncologic outcomes.A retrospective review of transurethral resections of bladder tumor from 1/2006 to 2/2018 was performed. The presence of detrusor muscle in the pathology report and transurethral resection specimen were extracted from records. Individual surgeon scorecards were created and distributed. Rates of detrusor muscle sampling were compared prior to and 12 months after distribution. Chart review was done to compare 3-year recurrence and progression outcomes before and after distribution of scorecards.The rate of detrusor muscle sampling increased from 36% (1,250/3,488) to 54% (202/373) (p=0.001) in the 12 months after scorecard distribution, ie from 30% (448/1,500) to 55% (91/165) (p0.001) in Ta tumors and from 47% (183/390) to 72% (42/58) (p0.001) in T1 tumors. Pathological reporting of muscle also improved for all samples (73%, 2,530/3,488 to 90%, 334/373, p0.001), Ta (75%, 1,127/1,500 to 94%, 155/165, p0.001) and T1 (93%, 362/390 to 100%, 58/58, p=0.04). On multivariate Cox regression analysis, the surgeon scorecard was associated with decreased 3-year risk of recurrence (HR 0.63, 95% CI 0.40-0.99).Creation and distribution of individual surgeon scorecards improved detrusor muscle sampling on transurethral resection and was associated with decreased risk of disease recurrence. Quality evaluation of transurethral resection of bladder tumor may contribute to improved outcomes of patients with nonmuscle invasive bladder cancer.

The synthesis and structures of N,N-dialkyldithiocarbamate complexes of barium are reported; the compounds crystallize as one-dimensional coordination polymers. In combination with a titanium dithiocarbamate precursor, the compounds are demonstrated as competent single-source precursors for the solution-based preparation of colloidal BaTiS3 nanorods.

A sanitation method that could continually clean and disinfect the air and surfaces in a hatchery could provide a second layer of microbial reduction on top of routine cleaning and disinfection. A gaseous dry hydrogen peroxide (DHP) system has been used in other facilities for this purpose and could have potential for use in chicken hatcheries. Because the DHP is a true gas and can permeate through the entire hatchery space, contact with eggs during storage and incubation could potentially interfere with normal hatching processes. Therefore, the aim of this study was to evaluate the effects of the DHP system on hatching parameters and chick quality. A total of 3,960 hatching eggs were collected from an ∼40-week-old Ross 308 broiler breeder flock and distributed in 2 treatments: treated and nontreated. For the treated group, the egg cooler was cleaned, and 1 DHP generator was placed inside. Two other DHP generators were placed in the common area outside as well. Both areas were treated for 7 D before placement of eggs, and then eggs were collected and placed inside the cooler over a 4-day period. Eggs were then stored for an additional 3 D after the last collection. Dry hydrogen peroxide levels were recorded each day during storage. For the nontreated group, all DHP machines were removed from the cooler and external room, and the egg cooler was cleaned. Eggs were collected in the same way for the control group as the treated group. After storage, eggs were placed into a single stage Natureform incubator. The eggs exposed to DHP showed higher (P

Two or more different live attenuated infectious bronchitis virus (IBV) vaccine types are often given to broilers to induce homologous protection as well as to broaden protection against other IBV types in the field. However, the ability of broilers to respond to three or four different antigenic types of IBV vaccine has not been examined experimentally. In this study, we vaccinated one-day-old broiler chicks by eyedrop with three or four different IBV vaccine types simultaneously. The presence and relative amount of each vaccine was examined in all of the birds by IBV type-specific real-time RT-PCR at 5 days post-vaccination and each vaccine was detected in all of the birds given that vaccine. The birds were challenged at 28 days of age and protection was measured by clinical signs, virus detection and by ciliostasis. Birds vaccinated with three different IBV types (Ark, Mass and GA98) were protected against challenge with each of those IBV types and were partially protected against challenge with the GA08 virus. Birds vaccinated with four different IBV types (Ark, Mass, GA98 and GA08) were protected against challenge with each of those IBV types with the exception of Mass challenged birds which clearly had 3/11 birds not protected based on individual ciliostasis scores, but had an average ciliostasis score of >50% which is considered protected. The results are important for the control of IBV because they indicate that simultaneous vaccination with up to four different IBV vaccine types can provide adequate protection against challenge for each type.

Feed conversion efficiency is among the most important factors affecting profitable production of poultry.Infections with parasitic nematodes can decrease efficiency of production, making parasite control through the use of anthelmintics an important component of health management. In ruminants and horses, anthelmintic resistance is highly prevalent in many of the most important nematode species, which greatly impacts their control. Recently, we identified resistance to fenbendazole in an isolate of Ascaridia dissimilis, the most common intestinal helminth of turkeys. Using this drug-resistant isolate, we investigated the impact that failure to control infections has on weight gain and feed conversion in growing turkeys. Birds were infected on D 0 with either a fenbendazole-susceptible or -resistant isolate, and then half were treated with fenbendazole (SafeGuard Aquasol) at 4- and 8-wk postinfection. Feed intake and bird weight were measured for each pen weekly throughout the study, and feed conversion rate was calculated. Necropsy was performed on birds from each treatment group to assess worm burdens at wk 7 and 9 postinfection. In the birds infected with the susceptible isolate, fenbendazole-treated groups had significantly better feed conversion as compared to untreated groups. In contrast, there were no significant differences in feed conversion between the fenbendazole-treated and untreated groups in the birds infected with the resistant isolate. At both wk 7 and 9, worm burdens were significantly different between the treated and untreated birds infected with the drug-susceptible isolate, but not in the birds infected with the drug-resistant isolate. These significant effects on feed conversion were seen despite having a rather low worm establishment in the birds. Overall, these data indicate that A. dissimilis can produce significant reductions in feed conversion, and that failure of treatment due to the presence of fenbendazole-resistant worms can have a significant economic impact on turkey production. Furthermore, given the low worm burdens and an abbreviated grow out period of this study, the levels of production loss we measured may be an underestimate of the true impact that fenbendazole-resistant worms may have on a commercial operation.

Infectious bronchitis virus (IBV) is a highly infectious and transmissible gammacoronavirus that is nearly impossible to control through biosecurity. Coronaviruses are RNA viruses with an enormous capacity for rapid replication and high rates of mutation, leading to a tremendous amount of genetic diversity. Viral evolution occurs when selection working on genetic diversity leads to new mutations being fixed in the population over time. For IBV, the emergence of variant viruses is likely due to a combination of selection acting on existing genetic diversity, as well as on newly created mutations as the virus replicates, or genetic drift. Immunity against IBV creates a strong selection pressure; however, immunity can also reduce the viral load, decreasing replication and the development of new mutations. Examining the balance between immunity reducing infection, replication, and genetic diversity, and immune pressure selecting for new variants, is extremely difficult at best. Nonetheless, vaccination and immunity do play a role in the emergence of new antigenic variants of IBV. To complicate the situation even more, coronaviruses can undergo recombination, and several studies in the literature report recombination between IBV vaccines and field viruses. However, to our knowledge, unlike genetic drift, recombination alone has not been shown to result in a new antigenic and pathogenic IBV type emerging to cause widespread disease in poultry. Vaccines against IBV that result in an immune population can reduce transmission (basic reproductive number

Purpose Bladder cancer is initially diagnosed and staged with a transurethral resection of bladder tumor (TURBT). Patient survival is dependent on appropriate sampling of layers of the bladder, but pathology reports are dictated as free text, making large-scale data extraction for quality improvement challenging. We sought to automate extraction of stage, grade, and quality information from TURBT pathology reports using natural language processing (NLP). Methods Patients undergoing TURBT were retrospectively identified using the Northwestern Enterprise Data Warehouse. An NLP algorithm was then created to extract information from free-text pathology reports and was iteratively improved using a training set of manually reviewed TURBTs. NLP accuracy was then validated using another set of manually reviewed TURBTs, and reliability was calculated using Cohen’s κ. Results Of 3,042 TURBTs identified from 2006 to 2016, 39% were classified as benign, 35% as Ta, 11% as T1, 4% as T2, and 10% as isolated carcinoma in situ. Of 500 randomly selected manually reviewed TURBTs, NLP correctly staged 88% of specimens (κ = 0.82; 95% CI, 0.78 to 0.86). Of 272 manually reviewed T1 tumors, NLP correctly categorized grade in 100% of tumors (κ = 1), correctly categorized if muscularis propria was reported by the pathologist in 98% of tumors (κ = 0.81; 95% CI, 0.62 to 0.99), and correctly categorized if muscularis propria was present or absent in the resection specimen in 82% of tumors (κ = 0.62; 95% CI, 0.55 to 0.73). Discrepancy analysis revealed pathologist notes and deeper resection specimens as frequent reasons for NLP misclassifications. Conclusion We developed an NLP algorithm that demonstrates a high degree of reliability in extracting stage, grade, and presence of muscularis propria from TURBT pathology reports. Future iterations can continue to improve performance, but automated extraction of oncologic information is promising in improving quality and assisting physicians in delivery of care.

Coccidiosis is an economically significant enteric disease caused by Eimeria species. Control of the disease is achieved through various means, including chemical anticoccidial drugs, ionophore antibiotics, and vaccination. Differences between the vaccines include the number of oocysts per dose (varying by as much as tenfold between vaccines), attenuation status of the oocysts, and the species present within the vaccine. Coccidia vaccines are typically administered via spray cabinet to day old chicks; however, a new gel-based delivery system that claims to elongate preening time and increase oocyst ingestion has been introduced and is specifically recommended for certain low dose vaccines. The purpose of this trial was to compare the application properties between high and low oocyst dose vaccines administered via gel and spray delivery systems to determine if application systems could potentially affect application success. The vaccines were mixed into gel and spray diluents per manufacturer's instructions, and samples were taken to assess how well the oocysts remained in suspension. Gel and spray application patterns were assessed by measuring the size and number of droplets applied onto a plexiglass sheet in a chick basket. Different size droplets were collected and oocyst enumeration and speciation were performed. Results show that no settling occurred after mixing in either diluent. As expected, the number of oocysts per droplet increased as droplet size of the spray administration increased but stayed constant in the uniform droplet size of gel administration. There was also a consistent number of oocysts found in each of the sections across the plexiglass sheet. Taken together, these data will aid poultry producers in deciding which delivery system will provide the best application in their production system.

The 2014 outbreak of clade 2.3.4.4A highly pathogenic avian influenza (HPAI) led to the culling of millions of commercial chickens and turkeys and death of various wild bird species. In this outbreak, older chickens and turkeys were commonly infected, and succumbed to clinical disease compared to younger aged birds such chicken broilers. Some experimental studies using waterfowl species have shown age-related differences in susceptibility to clinical disease with HPAI viruses. Here, we evaluate differences in H5 Hemagglutinin (HA) tissue binding across age groups, using recombinant H5 HA (rHA) proteins generated using gene sequences from low pathogenic (A/mallard/MN/410/2000(H5N2 (LPAIV)) and a HPAIV (A/Northern pintail/Washington/40964/2014(H5N2)) influenza A virus (IAV). Respiratory and intestinal tracts from chickens, ducks (Mallard, Pekin, Muscovy) and turkeys of different age groups were used to detect rHA binding with protein histochemistry, which was quantified as the median area of binding (MAB) used for statistical analysis. There were species and tissue specific differences in the rHA binding among the age groups, however, turkeys had significant differences in the HPAIV rHA binding in the respiratory tract, with younger turkeys having higher levels of binding in the lung compared to the older group. In addition, in the intestinal tract, younger turkeys had higher levels of binding compared to the older birds. Using LPAIV, similar species and tissues, specific differences were seen among the age groups, however, only turkeys had overall significant differences in the respiratory tract MAB, with the older birds having higher levels of binding compared to the younger group. No age-related differences were seen in the overall intestinal tract rHA binding. Age-related differences in rHA binding of the LPAIV and HPAIV demonstrated in this study may partially, but not completely, explain differences in host susceptibility to infection observed during avian influenza outbreaks and in experimental infection studies.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials., Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

Due to their ubiquity, management of parasites is a common and important factor for profitable production of poultry. Heterakis gallinarum, the cecal nematode, is the most common nematode parasite of poultry. While typically causing no pathology on its own, H. gallinarum is the vector of Histomonas meleagridis, a protozoan parasite that causes blackhead disease. Histomonas meleagridis is highly pathogenic in turkeys, potentially causing high mortality. In contrast, disease caused by H. meleagridis is much less severe in chickens, where it primarily reduces productivity without manifestations of clinical disease. There are no approved treatments for H. meleagridis, making control reliant on control of the helminth vector through the use of fenbendazole (FBZ) the only drug labeled for treatment of H. gallinarum in the United States We were contacted by an industry veterinarian regarding health-related concerns in a broiler-breeder house due to histomoniasis, despite frequent anthelmintic treatments. Since we had recently diagnosed resistance to FBZ in Ascaridia dissimilis, a closely related nematode of turkeys, we were interested to determine if H. gallinarum had also evolved resistance to FBZ. Heterakis gallinarum eggs were isolated from litter collected from the house and used to infect 108 chickens. Treatment groups included a non-treated control, a label-dose and a 2X-label dose of FBZ, with 36 birds per group divided into two replicate pens of 18 birds each. Birds were placed at 1-day post hatch, and at 3 weeks of age were infected with 150 embryonated eggs via oral gavage. Two weeks post infection, treated birds were administered a minimum of either a label- or 2X label-dose of FBZ in water for 5 days (SafeGuard® Aquasol, 1mg/kg BW). To ensure that all birds consumed the full intended dose at a minimum, the dosage was calculated using 1.25 times the average body weight. One-week post treatment, birds were euthanized, ceca removed, and parasites enumerated. Efficacy was calculated by comparing the total numbers of worms recovered from each treatment group to the numbers recovered in the non-treated control group. There were no significant differences in worm numbers recovered from any of the three groups (p-value=0.81). There also was no efficacy benefit to treatment with a 2X dose; H. gallinarum worm counts were reduced by 42.7% and 41.4%, for the label and 2X dosages, respectively. These data provide strong evidence that H. gallinarum has developed resistance to FBZ. Consequently, in houses infected with FBZ-resistant H. gallinarum, H. meleagridis will be able to cycle through the birds in an unrestricted manner. Further investigation is needed to determine the prevalence of resistance in H. gallinarum on chicken farms, but it is clear this has the potential to have a large-scale economic impact on the poultry industry. These data when viewed together with our recent findings of FBZ resistance in A. dissimilis, suggest that drug resistance in ascarid nematodes may be an important emerging problem on poultry operations.

Feed conversion efficiency is among the most important factors affecting profitable production of poultry. Infections with parasitic nematodes can decrease efficiency of production, making parasite control through the use of anthelmintics an important component of health management. In ruminants and horses, anthelmintic resistance is highly prevalent in many of the most important nematode species, which greatly impacts their control. Recently, we identified resistance to fenbendazole in an isolate of Ascaridia dissimilis, the most common intestinal helminth of turkeys. Using this drug-resistant isolate, we investigated the impact that failure to control infections has on weight gain and feed conversion in growing turkeys. Birds were infected on Day 0 with either a fenbendazole-susceptible or -resistant isolate, and then half were treated with fenbendazole (SafeGuard® Aquasol) at 4- and 8-weeks post infection. Feed intake and bird weight were measured for each pen weekly throughout the study, and feed conversion rate was calculated. Necropsy was performed on birds from each treatment group to assess worm burdens at weeks 7 and 9 post infection. In the birds infected with the susceptible isolate, fenbendazole-treated groups had significantly better feed conversion as compared to untreated groups. In contrast, there were no significant differences in feed conversion between the fenbendazole-treated and untreated groups in the birds infected with the resistant isolate. At both weeks 7 and 9, worm burdens were significantly different between the treated and untreated birds infected with the drug-susceptible isolate, but not in the birds infected with the drug-resistant isolate. These significant effects on feed conversion were seen despite having a rather low worm establishment in the birds. Overall, these data indicate that A. dissimilis can produce significant reductions in feed conversion, and that failure of treatment due to the presence of fenbendazole-resistant worms can have a significant economic impact on turkey production. Furthermore, given the low worm burdens and an abbreviated grow out period of this study, the levels of production loss we measured may be an underestimate of the true impact that fenbendazole-resistant worms may have on a commercial operation.

Clade 2.3.4.4, H5 subtype highly pathogenic avian influenza viruses (HPAIVs) have caused devastating effects across wild and domestic bird populations. We investigated differences in the intensity and distribution of the hemagglutinin (HA) glycoprotein binding of a clade 2.3.4.4 H5 HPAIV compared to a H5 low pathogenic avian influenza virus (LPAIV). Recombinant HA from gene sequences from a HPAIV, A/Northern pintail/Washington/40964/2014(H5N2) and a LPAIV, A/mallard/MN/410/2000(H5N2) were generated and, via protein histochemistry, HA binding in respiratory, intestinal and cloacal bursal tissue was quantified as median area of binding (MAB). Poultry species, shorebirds, ducks and terrestrial birds were used. Differences in MAB were observed between the HPAIV and LPAIV H5 HAs. We demonstrate that clade 2.3.4.4 HPAIV H5 HA has a broader host cell binding across a variety of bird species compared to the LPAIV H5 HA. These findings support published results from experimental trials, and outcomes of natural disease outbreaks with these viruses.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identified four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provided independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations were significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration was associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirmed the higher infiltration of class 2b tumors and demonstrated an association between higher immune cell infiltration and lower recurrence rates. Finally, a single-sample classification tool was built and the independent prognostic value of the transcriptomic classes was documented in 1306 validation samples. The classifier provides a framework for novel biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

Introduction:We evaluated the timing, frequency and antibiotic sensitivity of post-radical cystectomy urinary tract infections to guide an infection reduction initiative.Methods:A combined ...

Stage T1 bladder cancers have the highest progression and recurrence rates of all non-muscle-invasive bladder cancers (NMIBCs). Most T1 cancers are treated with bacillus Calmette-Guerin (BCG), but many will progress or recur, and some T1 patients will die from bladder cancer. Particularly aggressive tumors could be treated with early cystectomy. To better understand the molecular heterogeneity of T1 cancers, we performed transcriptome profiling and unsupervised clustering, and identified five consensus subtypes of T1 tumors treated with repeat transurethral resection (reTUR) and induction and maintenance BCG. The T1-LumGU subtype was associated with carcinoma in situ (CIS; six/13, 46% of all CIS), had high E2F1 and EZH2 expression, and was enriched in E2F target and G2M checkpoint hallmarks. The T1-Inflam subtype was inflamed and infiltrated with immune cells. While most T1 tumors were classified as luminal papillary, the T1-TLum subtype had the highest median luminal papillary score and FGFR3 expression, no recurrence events, and the fewest copy number gains. T1-Myc and T1-Early subtypes had the most recurrences (14/30 within 24 mo), the highest median MYC expression, and, when combined, had significantly worse recurrence-free survival than the other three subtypes. T1-Early had five (38%) recurrences within the first 6 mo of BCG, and repressed IFN-α and IFN-γ hallmarks and inflammation. We developed a single-patient T1 classifier and validated our subtype biology in a second cohort of T1 tumors. Future research will be necessary to validate the proposed T1 subtypes and to determine if therapies can be individualized for each subtype. PATIENT SUMMARY: We identified and characterized expression subtypes of high-grade stage T1 bladder cancer that are biologically heterogeneous and have variable responses to bacillus Calmette-Guerin treatment. We validated the subtypes and describe a single-patient classifier.

Stage T1 bladder cancers invade the lamina propria of the bladder and, despite sharing many of the genetic features of muscle-invasive bladder cancers, are classified as non-muscle-invasive or ‘superficial’ tumours. Yet, patients with T1 bladder cancer have an overall mortality of 33% and a cancer-specific mortality of 14% at three years after diagnosis, suggesting that these patients have a high risk of progression and, accordingly, require meticulous surgery, endoscopic surveillance and clinical decision-making. We hypothesize that the variability in the outcomes of patients with T1 bladder cancer is a result of both tumour heterogeneity and pathological staging, as well as inconsistencies in risk stratification, endoscopic resection and schedules of delivery of BCG. Owing to limitations in clinical staging, patients with T1 bladder cancer are at risk of both undertreatment with persistent use of BCG despite recurrence, and overtreatment with early cystectomy. Understanding the molecular features of T1 bladder cancers and how they respond to BCG therapy could improve biomarkers for risk stratification to align therapy with biological risk. Patients with stage T1 bladder cancer require meticulous management owing to their high-risk of recurrence, progression and death. Here, Jordan and Meeks describe the natural history, diagnosis, and treatment of T1 bladder cancer, highlighting key challenges and areas of future investigation.

Almost all commercial poultry are vaccinated against avian coronavirus infectious bronchitis virus (IBV) using live attenuated vaccines mass administered by spray at day of hatch. Although many different types of IBV vaccines are used successfully, the ArkDPI serotype vaccine, when applied by spray, does not infect and replicate sufficiently to provide protection against homologous challenge. In this study, we examined a different Ark vaccine strain (Ark99), which is no longer used commercially due to its reactivity in one day old chicks, to determine if it could be further attenuated by passage in embryonated eggs but still provide adequate protection. Further attenuation of the Ark99 vaccine was achieved by passage in embryonated eggs but ArkGA P1, P20, and P40 (designated ArkGA after P1) were still too reactive to be suitable vaccine candidates. However, ArkGA P60 when given by spray had little or no vaccine reaction in one day old broiler chicks, and it induced protection from clinical signs and ciliostasis following homologous challenge. In addition, vaccinated and challenged birds had significantly less challenge virus, an important measure of protection, compared to non-vaccinated and challenged controls. The full-length genomes of viruses from egg passages 1, 20, 40, and 60 were sequenced using the Illumina platform and the data showed single nucleotide polymorphisms (SNPs) had accumulated in regions of the genome associated with viral replication, pathogenicity, and cell tropism. ArkGA P60 accumulated the most SNPs in key genes associated with pathogenicity (polyprotein gene 1ab) and cell tropism (spike gene), compared to previous passages, which likely resulted in its more attenuated phenotype. These results indicate that the ArkGA P60 vaccine is safe for spray vaccination of broiler chicks and induces suitable protection against challenge with pathogenic Ark-type virus.

Background: Radical cystectomy (RC) is a morbid procedure with frequent complications that may benefit from implementation of an enhanced recovery after surgery (ERAS) protocol. Objective: To examine the benefits of a multimodal analgesic plan that uses continuous transversus abdominis plane (TAP) blockade as part of an ERAS protocol after RC. Methods: A retrospective comparison of consecutive patients undergoing RC over a 4-year period was conducted. Patients were designated as having surgery either before or after implementation of an ERAS protocol. A major component of the ERAS protocol was a multi-modal analgesia plan with TAP blockade. Patient demographics, comorbidities, operative details, and outcomes, including days to flatus, bowel movement (BM), narcotic usage, and length of stay (LOS) were compared. Results: In total, 171 patients were included: 100 pre-ERAS and 71 ERAS. There were no differences in age, smoking status, operative approach, or diversion type. The patients in the ERAS cohort were less likely to be male, had a higher median BMI, and more likely to have received neoadjuvant chemotherapy. Total and early postoperative narcotic use were lower in the ERAS cohort: 89 vs. 336 mg (p

To evaluate the rate of venous thromboembolism (VTE) after nephrectomy with specific focus on event timing and location (before or after hospital discharge) in order to identify modifiable risk factors and establish benchmarks for preventive interventions. Using the ACS-NSQIP database, we identified patients undergoing nephrectomy from 2006 to 2012. Patients were analyzed in two cohorts: collectively and by surgical approach [open vs. lap/robotic (MIS)]. Rates of deep vein thrombosis (DVT) and pulmonary embolus (PE) were assessed and time to each event was established in relation to discharge status. Logistic regression analysis was performed to assess association between preoperative risk factors, surgical variables, and VTE. In total, 13,208 patients met inclusion criteria. The overall rate of VTE was 1.2% (PE = 0.5% and DVT = 0.8, 0.1% DVT and PE). Using regression analysis, diabetes, dependent functional status, and longer operative time were associated with higher odds of DVT. For PE, dyspnea, disseminated cancer, and longer operative time were significant associations. The rate of VTE was higher in open surgery compared to MIS (2 vs. 0.8%, p

The coccidian species

An important factor in efficient production of poultry is management of parasites. Ascaridia dissimilis is the most prevalent small intestinal nematode parasite of turkeys with up to 100% of flocks infected. High worm burdens can cause necrotic enteritis leading to high mortality in flocks. Recently, we were made aware of multiple cases where high burdens were seen at slaughter despite the administration of anthelmintics at frequent intervals, suggesting that resistance may have evolved in A. dissimilis. To address this issue, we obtained eggs of A. dissimilis from 4 commercial turkey farms and performed controlled efficacy tests to determine if fenbendazole resistance was present. Three farms had histories of frequent use of fenbendazole and worms found at slaughter, suggesting they may have resistance, and one was an organic farm where we had no additional history other than the farm had transitioned to organic production a few years earlier. For each worm isolate there were 2 treated and 2 untreated groups containing 9 birds each, with all groups being replicated in 2 separate rooms. Birds were infected with approximately 200 infective eggs, and treated groups received fenbendazole in the water (SafeGuard Aquasol, 1mg/kg) for 5 consecutive days starting on day 24 post-infection. One week after the last treatment birds were necropsied, intestinal contents were collected and worms enumerated. Three of the four isolates demonstrated greater than 99% efficacy, indicating they were fully susceptible to fenbendazole. However, the fourth isolate demonstrated a significantly reduced efficacy of 63.89%, indicating the presence of resistance. Interestingly, this was the organic farm, whereas the 3 farms with “suspected” resistance all turned out to be fully susceptible. Given that 1 randomly acquired isolate of A. dissimilis, out of 4 tested, demonstrated resistance in this study, fenbendazole resistance may be a much larger problem on turkey farms than is currently recognized. Additional studies are needed to determine the prevalence of resistance, as well as the economic impact that resistant A. dissimilis have on turkey production.

Intestinal inflammation may provide a growth advantage forContribución de la coinfección por

This is a case of emphysematous cystitis with a rare complication of bladder rupture requiring surgical intervention in a diabetic man who presented with urinary retention and abdominal pain, with a large amount of intraperitoneal free air on computed tomography scan. Keywords: Emphysematous cystitis, Bladder rupture, Pneumoperitoneum

Infectious bronchitis virus is an important respiratory pathogen in chickens. The IBV S1 spike is a viral structural protein that is responsible for attachment to host receptors and is a major target for neutralizing antibodies. To date, there is no experimentally determined structure for the IBV S1 spike. In this study, we sought to find a predicted tertiary structure for IBV S1 using I-TASSER, which is an automated homology modeling platform. We found that the predicted structures obtained were robust and consistent with experimental data. For instance, we observed that all four residues (38, 43, 63, and 68) that have been shown to be critical for binding to host tissues, were found at the surface of the predicted structure of Massachusetts (Mass) S1 spike. Together with antigenicity index analysis, we were also able to show that Ma5 vaccine has higher antigenicity indices at residues close to the receptor-binding region than M41 vaccine, thereby providing a possible mechanism on how Ma5 achieves better protection against challenge. Examination of the predicted structure of the Arkansas IBV S1 spike also gave insights on the effect of polymorphisms at position 43 on the surface availability of receptor binding residues. This study showcases advancements in protein structure prediction and contributes useful, inexpensive tools to provide insights into the biology of IBV., Highlights • Tertiary structure of the S1 spike glycoprotein of IBV was predicted using I-TASSER. • Putative receptor binding residues were mapped on S1 predicted tertiary structure. • Mapping of important regions in S1 offer insights on outcomes of IBV vaccination.

Sequencing avian infectious bronchitis virus spike genes re-isolated from vaccinated chicks revealed that many sequence changes are found on the S1 spike gene. In the ArkDPI strain, Y43H and ∆344 are the two most common changes observed. This study aims to examine the roles of Y43H and ∆344 in selection in vivo. Using recombinant ArkDPI S1 proteins, we conducted binding assays on chicken tracheas and embryonic chorioallantoic membrane (CAM). Protein histochemistry showed that the Y43H change allows for enhanced binding to trachea, whereas the ArkDPI S1 spike with H43 alone was able to bind CAM. Using Western blot under denaturing conditions, ArkDPI serotype-specific sera did not bind to S1 proteins with ∆344, suggesting that ∆344 alters antigenicity of S1. These findings are important because they propose that specific changes in S1 enhances virus fitness by more effective binding to host tissues (Y43H) and by evading a vaccine-induced antibody response (∆344)., Graphical abstract fx1, Highlights • Binding behaviors of recombinant IBV ArkDPI vaccine S1 proteins are examined. • Mutation Y43H enhances binding to mature tracheal tissue but not embryonic tissue. • A ∆344 mutation alters epitopes on S1 preventing antibody binding. • These two mutations enhance the vaccine viruses' overall fitness in chickens.

Commercial broilers are commonly exposed to gaseous ammonia (NH3) originating from degradation of nitrogen-containing excreta in the litter during the grow-out period. Ammonia concentrations in the air are higher in poorly ventilated houses and appear to coincide with the elevated incidence of respiratory disease occurring during the winter months. This study examined the effect of NH3 on the immune response to infectious bronchitis virus (IBV) vaccination and protection against homologous serotype challenge in commercial broiler chickens. One-day-old chicks were administered IBV vaccine and exposed to 30–60 ppm of NH3. At 28 DOA, birds were challenged oculonasally with a pathogenic homologous IBV, and protection was measured by viral detection, clinical signs, ciliostasis, and presence of airsacculitis. IBV-specific serum IgG and lacrimal fluid IgA titers, as well as Harderian gland (HG) immune cell phenotypes, were evaluated. Ammonia exposure was associated with an increased incidence of airsacculitis among non-vaccinated, challenged birds. Vaccinated, NH3-exposed birds were completely protected from IBV challenge. Ammonia had subtle effects on cilia morphology and function but did not affect vaccine or challenge virus replication and clearance, clinical signs, ciliostasis, tracheal histopathology scores, or immune responses. In the HG of vaccinated birds, the percent of leukocytes, MHC I+/MHC IIhi expression, IgM+ expression, and CD8+ expression was increased, while mucosal IgA and serum IgG titers were nominal. Non-vaccinated, IBV-challenged birds exhibited an increased percent of leukocytes, MHC I+/MHC IIhi expression, and IgM+ expression in the HG at 5 dpc, followed by increased mucosal IgA and serum IgG titers and CD8+ expression at 10–14 dpc. In contrast, vaccinated, IBV-challenged birds had a minimal increase in MHC I+/MHC IIhi expression, and serum IgG antibody titers in vaccinated birds increased rapidly. The results indicate that commercial broilers exposed to moderate levels of ambient NH3 are equally protected against IBV challenge if appropriately vaccinated, and the absence of robust immune activation in vaccinated, challenged birds suggests that the challenge virus was efficiently neutralized before establishing infection. In contrast, ambient NH3 exposure was associated with a higher incidence of airsacculitis in non-vaccinated, challenged birds, despite the apparent lack of differences in the immune response between birds in the NH3-exposed and NH3 control groups.

Bladder reconstructions are commonly performed in patients with neurogenic bladders with a high rate of complications. We seek to help guide the evaluation and management of these complications by reviewing the available data. Augmentation cystoplasty and concomitant procedures such as continent catheterizable channels, bladder neck closure, and bladder neck sling can provide long-term solutions for patients with poorly compliant, high-pressure bladders or refractory detrusor overactivity. While these techniques improve symptoms and protect against upper tract deterioration, patients are exposed to new risks including bladder perforation, increased malignancy rates, urolithiasis, surgical failures, and persistent symptoms. The overall rate of reoperation is high. Evaluation with urodynamics and endoscopy, when indicated, remain critical tools to protect this patient population. Use of clean intermittent catheterization has helped popularize bladder reconstructive surgery, but a strict regimen is required to minimize postoperative risks in the long term. Additionally, various surgical techniques can be utilized to manage complications after bladder reconstruction, and concurrent use of anticholinergics and onabotulinum toxin injections can further mitigate these reconstructive failures. Bladder reconstruction can provide excellent long-term solutions, but patients are at a high risk of long-term complications. Appropriate patient counseling, close follow-up, and timely evaluation are crucial in managing the long-term complications of bladder reconstruction surgery.

studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark-DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated poorly and failed to adequately protect broilers against homologous virus challenge, whereas the same vaccine given by eye-drop did replicate and the birds were protected following homologous virus challenge. To determine if mechanical damage following spray application plays a role in failure of the Ark-DPI vaccine, we examined the morphology of three Ark-DPI vaccines from different manufacturers using an electron microscope and included a Massachusetts (Mass) vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine had significantly (P0.005) fewer spikes than the other two Ark-DPI vaccines. We also found that the Ark-DPI and Mass vaccines had significantly (P0.005) fewer spike proteins per virus particle when compared to their respective challenge viruses. This observation is interesting and may provide some insight into the mechanism behind infectious bronchitis virus attenuation. No obvious differences were observed in virus morphology and no consistent trend in the number of spikes per virion was found in before- and after-spray samples. We also determined the vaccine titer before and after spray in embryonated eggs and found that both Ark-DPI and Mass vaccines had a similar drop in titer, 0.40 logi and 0.310 logi, respec10ively. Based on these data, it appears that mechanical damage to the Ark-DPI vaccine is not occurring when delivered by a hatchery spray cabinet, suggesting that some other factor is contributing to the failure of that vaccine when given by that method.

Coccidiosis is an economically significant disease of poultry caused by species of Eimeria, a parasitic protozoan. Disease can result in poor feed conversion, reduced weight gain, and can lead to the development of necrotic enteritis. For prevention of coccidiosis, poultry are commonly vaccinated with a live, sporulated oocysts mass applied with a vaccination cabinet in the hatchery. Traditionally, coccidia vaccines have been applied by coarse spray in a water based diluent, however, new technology using gel diluents has entered the US market. Gel diluents can have variable viscosities and are “dropped” onto chicks with an applicator bar. It is thought that gel droplets remain intact on the birds for longer than water based droplets, allowing more time for preening and ingestion of oocysts. In this experiment, the efficacy of a commercial coccidia vaccine applied with a water based diluent, a more viscous gel diluent, and a less viscous gel diluent was compared. Fecal samples were collected at multiple time points post-vaccination to quantify vaccine oocyst shedding. Shedding in the first cycle (days 5 to 8 post-vaccination) was related to the number of oocysts received from each application method, where the groups receiving higher doses shed more oocysts. However, a decrease in shedding was seen for the more viscous gel group in the second cycle (days 12 to 15 post-vaccination). Chickens were challenged with Eimeria maxima oocysts and 7 days post-challenge body weight gains and gross and microscopic lesions were recorded to evaluate protection levels for the different vaccine applications. All vaccinated groups appeared to be protected based on body weight gain and lesion scoring. The results of this project indicate that all vaccine applications are effective at protecting against Eimeria maxima challenge when using a proper dose of vaccine that allows for repeated oocyst cycling in the litter post-vaccination.

The Arkansas Delmarva Poultry Industry (ArkDPI) infectious bronchitis virus (IBV) vaccine is effective when administered by eye drop, where the vaccine virus is able to infect and replicate well in birds and is able to induce protection against homologous challenge. However, accumulating evidence indicates that the ArkDPI vaccine is ineffective when applied by hatchery spray cabinet using the same manufacturer-recommended dose per bird. For this study, we aimed to determine the minimum infectious dose for the spray-administered ArkDPI vaccine, which we designate as the dose that achieves the same level of infection and replication as the eye drop-administered ArkDPI vaccine. To this end, we used increasing doses of commercial ArkDPI vaccine to vaccinate 100 commercial broiler chicks at day of hatch, using a commercial hatchery spray cabinet. The choanal cleft of each bird was swabbed at 7 and 10 days postvaccination, and real-time reverse-transcriptase PCR was performed. We observed that the level of infection and replication with spray vaccination matches with that of eye drop vaccination when chicks received 100 times the standard dose for the commercial ArkDPI vaccine. We further examined the S1 spike gene sequence from a subset of reisolated ArkDPI vaccine virus samples and observed that certain nucleotide changes arise in vaccine viruses reisolated from chicks, as previously reported. This suggests that the ArkDPI vaccine has a certain virus subpopulation that, while successful at infecting and replicating in chicks, represents only a minor virus subpopulation in the original vaccine. Thus, the minimum infectious dose for the ArkDPI vaccine using a hatchery spray cabinet appears to be dependent on the amount of this minor subpopulation reaching the chicks.

Germ cells (GCs) are critically important as the vehicle that passes genetic information from one generation to the next. Correct development of these cells is essential and perturbation in their development often leads to reproductive failure and disease. Despite the importance of GCs, little is known about the mechanisms underlying the acquisition and maintenance of the GC character. Using a reprogramming strategy, we demonstrate that overexpression of ectopic transcription factors in embryonic fibroblasts can lead to the generation of chicken induced primordial germ cells (ciPGCs). These ciPGCs express pluripotent markers POU5F1, SSEA1, and the GC defining proteins, CVH and DAZL, closely resembling in vivo sourced PGCs instead of embryonic stem cells. Moreover, CXCR4 expressing ciPGCs were capable of migrating to the embryonic gonad after injection into the vasculature of stage 15 embryos, indicating the acquisition of a GC fate in these cells. Direct availability of ciPGCs in vitro would facilitate the study of GC development as well as provide a potential strategy for the conservation of important genetics of agricultural and endangered birds using somatic cells.

The chicken is a well-established model system for studying developmental biology and is recognized as one of the top food production animals in the world. For this reason the chicken is an excellent candidate for transgenic applications, as the technology can be applied to both areas of research. Transgenic technology has not been broadly utilized in the chicken model, however, primarily due to difficulties in targeting germ cells and establishing germ line transmission. Transgenic technologies using non-replicating viral particles have been used in the chick, but are unsuitable for many applications because of size and sequence restraints and low efficiency. To create a more versatile method to target chick germ line stem cells, we utilized the transposable element system piggyBac paired with an in vivo transfection reagent, JetPEI. piggyBac has been previously shown to be highly active in mammalian cells and will transpose into the chicken genome. Here, we show that JetPEI can transfect multiple chick cell types, most notably germline stem cells. We also show that pairing these two reagents is a viable and reproducible method for long-term expression of a transgene in the chicken. Stable expression of the green fluorescent protein (GFP) transgene was seen in multiple tissue types including heart, brain, liver, intestine, kidney and gonad. Combining an in vivo transfection strategy with the PB system provides a simple and flexible method for efficiently producing stable chimeric birds and could be used for production of germ line transgenics.

The coccidian species Eimeria is a parasitic protozoan that causes the gastrointestinal disease coccidiosis in numerous vertebrate species. Incidence of the disease in commercial chickens produces drastic economic losses. Traditionally, detection of Eimeria has been performed using classical methods such as observation of oocyst morphology. However, molecular methods to detect and speciate Eimeria are becoming more prevalent. The 18S ribosomal gene, in particular, has been a widely used DNA amplification target for detection of Eimeria. Although the full-length gene is typically used for this purpose, newer research targeting shorter regions of the gene is being performed. This study investigated the suitability of a 120-base pair (bp) DNA bar code within the 18S gene for species differentiation. When comparing sequence variation from the Eimeria species infecting chickens, shortening the 18S gene to the 120-bp highly variable region provided increased species differentiation, while also reducing intraspecies variation. This DNA bar code is useful for distinction of the Eimeria species infecting chickens and should be considered for future molecular detection assays and metagenomic sequencing.

Intestinal inflammation may provide a growth advantage for Salmonella and enhance its systemic spread in chickens. Salmonella triggers intestinal inflammation in the host by using type III secretion systems (T3SS) and produces the inflammatory end product tetrathionate. In mice, tetrathionate respiration confers a growth advantage for Salmonella Typhimurium over the competitive microbiome in the inflamed intestine. Coccidia also promote intestinal inflammation and enhance Salmonella intestinal growth and systemic spread in chickens. The objective of this study was to evaluate the contribution of inflammation, induced by Eimeria spp. or Salmonella Typhimurium, to Salmonella colonization and dissemination in chickens. In addition, the fitness costs associated with defects in tetrathionate reductase and T3SS associated with Salmonella Pathogenicity Island 1 or 2 (SPI-1 or SPI-2) were evaluated in in vivo competition experiments with wild-type Salmonella strain, with or without Eimeria coinfection. One-day-old specific-pathogen-free chickens were orally inoculated with a sham inoculum or with 4 × 102Eimeria oocysts cocktail of Eimeria tenella, Eimeria acervulina, Eimeria maxima, and Eimeria mitis. At 6 days of age, birds were orally administered a 1:1 ratio of Salmonella Typhimurium wild-type and mutant deficient in tetrathionate reductase, SPI-1, or SPI-2 (108 colony forming units/bird). Ceca, livers, and drumsticks were collected at 3, 7, 14, and 42 days after Salmonella infection, for bacteriology. Intestinal inflammation was scored by histology. Significantly higher intestinal inflammation was observed in challenge groups compared with the control. However, there were no significant differences in intestinal inflammation scores between groups coinfected with both Eimeria spp. and Salmonella Typhimurium and birds infected with Salmonella alone, and Eimeria coinfection did not increase Salmonella prevalence or abundance. Contrary to mouse studies, tetrathionate reductase did not enhance Salmonella Typhimurium cecal colonization or systemic spread in chickens. SPI-1 and SPI-2 played a significant role in Salmonella dissemination and cecal colonization in chickens, respectively.

Infectious bronchitis virus (IBV) is a significant respiratory pathogen of commercial poultry that causes millions of dollars in lost revenue worldwide each year. Even though the poultry industry extensively vaccinates against IBV, emergence of new serotypes and variants continually occur, making control of the disease difficult. Current mass application strategies for IBV vaccines are inefficient and frequently result in vaccination failures. Novel vaccine technology development has been slow, and is hindered by the constraints of large-scale poultry production. Further complicating the situation is the lack of knowledge of IBV protein and host cell interactions, making targeted vaccine intervention strategies near impossible. Taken together, it is easy to see why this disease remains significant in poultry production. This review outlines the current situation as it relates to IBV control, including vaccination, vaccines, and development of immunity, and recent developments in vaccine technology that may provide better protection in the future.

Purpose To evaluate the rate of venous thromboembolism (VTE) after nephrectomy with specific focus on event timing and location (before or after hospital discharge) in order to identify modifiable risk factors and establish benchmarks for preventive interventions.

Complementary diaminopyridine–flavin dyads that provide liquid crystalline systems have been synthesised. The mesophases possess well-defined molecular architectures, thermal stability and wide ranges. Furthermore, chiral centres have been introduced to explore the role chirality plays on the end morphology. The introduction of stereo-centres into these systems offers effective control over mesophase morphology and generates well-defined columnar liquid crystals.

Polyethyleneimine (PEI) is used as a scaffold for integrated top-down/bottom-up fabrication. In this synergistic strategy, patterned PEI surfaces are created using thermal nanoimprint lithography (NIL) using a sacrificial polystyrene (PS) overlayer. These imprinted surfaces act as versatile templates for assembling nanoparticles and dyes, with the amine groups of the PEI enabling electrostatic assembly, carbodiimide coupling, and dithiocarbamate attachment to the nanoimprinted features. The efficient assembly of particles and dyes is confirmed through fluorescence and atomic force microscopy. In these studies the PS overlayer serves two roles. First, the PS layer protects the PEI surface during the plasma-etch removal of the residual layer of the NIL process. Second, the PS overlayer serves as a mask, enabling sequential functionalization of the sides and the tops of the PEI features.

Electron-beam lithography is used to pattern either cationic polyvinyl N-methyl pyridine or anionic sulfonated polystyrene polymers, that act as negative resists, to produce templates for electroless deposition and the electrostatic assembly of metallic, magnetic, or semiconductor nanoparticles.

Avian species are among the most diverse vertebrates on our planet and significantly contribute to the balance of the ecology. They are also important food source and serve as a central animal model to decipher developmental biology and disease principles. Derivation of induced pluripotent stem cells (iPSCs) from avian species would enable conservation of genetic diversity as well as offer a valuable cell source that facilitates the use of avian models in many areas of basic and applied research. In this chapter, we describe methods used to successfully reprogram quail fibroblasts into iPSCs by using human transcription factors and the techniques critical to the characterization of their pluripotency.

In this study, we examined the association among clinical signs, ciliostasis, virus detection, and histopathology for evaluating protection of vaccinated chickens against homologous and heterologous infectious bronchitis virus (IBV) challenge. At 5 days following challenge with IBV, we found a good correlation among clinical signs, ciliostasis in the trachea, challenge virus detection, and microscopic lesions in the trachea, with all four criteria being negative in fully protected birds and positive in fully susceptible birds. In partially protected birds we observed clinical signs and detected challenge virus; however, the ciliated epithelium was intact. In a second experiment, we challenged fully protected, partially protected, and fully susceptible birds with IBV, and then at 5 days postchallenge we gave the birds an opportunistic bacterium intranasally. Twenty Bordetella avium colonies were recovered from one of five fully protected birds, and only five colonies were isolated from two of five partially protected birds without ciliostasis, whereas in birds with ciliostasis, numerous colonies were isolated. Obviously, decreasing IBV infection and replication in the upper respiratory tract will decrease transmission and mutations, leading to variant viruses, and herein we demonstrate that protection of the cilia will decrease secondary bacterial infections, which have been shown to lead to condemnations and increased mortality. Thus, it appears that examining both criteria would be important when evaluating IBV vaccine efficacy.

[reaction: see text] We report the synthesis of flavin-stoppered hydrogen bonded [2]rotaxanes 1 and 2. We also report the electrochemically controllable properties of these systems in solution, and for derivative 2, as an electropolymerized thin film.

Avian species are among the most diverse vertebrates on our planet and significantly contribute to the balance of the ecology. They are also important food source and serve as a central animal model to decipher developmental biology and disease principles. Derivation of induced pluripotent stem cells (iPSCs) from avian species would enable conservation of genetic diversity as well as offer a valuable cell source that facilitates the use of avian models in many areas of basic and applied research. In this chapter, we describe methods used to successfully reprogram quail fibroblasts into iPSCs by using human transcription factors and the techniques critical to the characterization of their pluripotency.