Barium and titanium dithiocarbamates as precursors for colloidal nanocrystals of emerging optoelectronic materials.

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.

Molecular Evolution of Infectious Bronchitis Virus and the Emergence of Variant Viruses Circulating in the United States.

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 R0 less than 1), making vaccines for IBV the best control strategy available. However, IBV control remains extremely challenging because of the high number of antigenic variants causing disease in poultry and a limited number of vaccines that mostly provide only partial protection against infection and replication of those variants. Currently, there is one major variant IBV circulating in all sectors of US commercial poultry production: DMV/1639/11. This virus was initially detected in 2011, but only began causing significant disease in 2014/2015. Since then, it has affected all three sectors of poultry production (layers, breeders, broilers) and continues to predominate in certain regions of the United States. Additionally, a previously classified variant IBV, which is no longer considered a variant virus, GA08, is highly prevalent. This is attributed to heavy GA08-type IBV vaccine usage because disease caused by the GA08-type virus is rare. Interestingly, the major IBV detected in poultry for several decades, ArkDPI, is no longer among the most detected viruses in the United States. This change corresponds to the shift away from ArkDPI vaccine usage in the broiler sector as GA08 vaccine usage has increased and highlights the role IBV vaccines play in influencing viral populations in commercial chickens.

Estudio recapitulativo- Evolución molecular del virus de la bronquitis infecciosa y aparición de virus variantes que circulan en los Estados Unidos. El virus de la bronquitis infecciosa es un gammacoronavirus altamente infeccioso y transmisible que es casi imposible de controlar mediante bioseguridad. Los coronavirus son virus ARN con una enorme capacidad de replicación rápida y altas tasas de mutación, lo que conduce a una gran cantidad de diversidad genética. La evolución viral ocurre cuando la selección que tiene influencia sobre la diversidad genética conduce a la fijación de nuevas mutaciones en la población a lo largo del tiempo. En el caso del virus de la bronquitis infecciosa, la aparición de variantes virales probablemente se deba a una combinación de selección que actúa sobre la diversidad genética existente, así como a mutaciones recién creadas a medida que el virus se replica o desarrolla deriva genética. La inmunidad contra el virus de la bronquitis infecciosa crea una fuerte presión de selección; sin embargo, la inmunidad también puede reducir la carga viral, disminuyendo la replicación y el desarrollo de nuevas mutaciones. La evaluación del equilibrio entre la inmunidad que reduce la infección, la replicación, la diversidad genética y la presión inmune que selecciona nuevas variantes, es extremadamente difícil en el mejor de los casos. No obstante, la vacunación y la inmunidad desempeñan un papel en la aparición de nuevas variantes antigénicas del virus de bronquitis. Para complicar aún más la situación, los coronavirus pueden someterse a recombinación y varios estudios en la literatura describen acerca de la recombinación entre las vacunas de bronquitis infecciosa y los virus de campo. Sin embargo, hasta donde se conoce, a diferencia de la deriva genética, no se ha demostrado que la recombinación por sí sola dé como resultado nuevos tipos antigénicos o patógenos del virus de la bronquitis infecciosa que causen una enfermedad generalizada en la avicultura. Las vacunas contra el virus de la bronquitis infecciosa que dan como resultado poblaciones inmune pueden reducir la transmisión (número reproductivo básico R0 menor que 1), lo que hace que las vacunas contra bronquitis infecciosa sean la mejor estrategia de control disponible. Sin embargo, el control de la bronquitis infecciosa sigue siendo un gran desafío debido a la gran cantidad de variantes antigénicas que causan enfermedades en la avicultura y a una cantidad limitada de vacunas que, en su mayoría, brindan solo una protección parcial contra la infección y la replicación de esas variantes. Actualmente, existe una variante principal del virus de la bronquitis infecciosa que circula en todos los sectores de la producción avícola comercial de los Estados Unidos: la variante DMV/1639/11. Este virus se detectó inicialmente en 2011, pero solo comenzó a causar una enfermedad significativa entre los años 2014/2015. Desde entonces, ha afectado a los tres sectores de la producción avícola (ponedoras, reproductoras, pollos de engorde) y continúa predominando en ciertas regiones de los Estados Unidos. Además, una variante de este virus previamente clasificada, que ya no se considera una variante, el virus GA08, es muy prevalente. Esto se atribuye al uso intensivo de la vacuna contra este tipo GA08 porque la enfermedad causada por el virus de tipo GA08 es poco común. Curiosamente, el principal virus de la bronquitis detectado en la avicultura durante varias décadas, ArkDPI, ya no se encuentra entre los virus más detectados en los Estados Unidos. Este cambio corresponde a la disminución en el uso de la vacuna ArkDPI en el sector de pollos de engorde a medida que el uso de la vacuna GA08 ha aumentado y se destaca el papel que desempeñan las vacunas de bronquitis infecciosa en la influencia de las poblaciones virales en los pollos comerciales.

Surgeon Scorecards Improve Muscle Sampling on Transurethral Resection of Bladder Tumor and Recurrence Outcomes in Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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) (p <0.001) in Ta tumors and from 47% (183/390) to 72% (42/58) (p <0.001) in T1 tumors. Pathological reporting of muscle also improved for all samples (73%, 2,530/3,488 to 90%, 334/373, p <0.001), Ta (75%, 1,127/1,500 to 94%, 155/165, p <0.001) 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). CONCLUSIONS: 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.

Protection following simultaneous vaccination with three or four different attenuated live vaccine types against infectious bronchitis virus.

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.

The Contribution of Eimeria Coinfection and Intestinal Inflammation to Cecal Colonization and Systemic Spread of Salmonella Typhimurium Deficient in Tetrathionate Reductase or Type III Secretion Systems Salmonella Pathogenicity Island 1 or 2.

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.

Contribución de la coinfección por Eimeria y de la inflamación intestinal a la colonización cecal y a la propagación sistémica de Salmonella Typhimurium deficiente en tetrationato reductasa o de sistemas de secreción de tipo III de islas de patogenicidad 1 o 2 de Salmonella. La inflamación intestinal puede proporcionar una ventaja para el crecimiento de Salmonella y aumentar su propagación sistémica en pollos. Salmonella desencadena la inflamación intestinal en el huésped mediante el uso de sistemas de secreción tipo III (T3SS) y produce el producto final inflamatorio, tetrationato. En ratones, la respiración con tetrationato confiere una ventaja de crecimiento para Salmonella Typhimurium sobre el microbioma competitivo en el intestino inflamado. Coccidia también promueve la inflamación intestinal y mejora el crecimiento intestinal de Salmonella y la propagación sistémica en pollos. El objetivo de este estudio fue evaluar la contribución de la inflamación, inducida por Eimeria spp. o Salmonella Typhimurium, en la colonización y diseminación de Salmonella en pollos. Además, se evaluaron los costos de aptitud asociados con defectos en la tetrationato reductasa y T3SS asociados con las islas de patogenicidad 1 o 2 de Salmonella (SPI-1 o SPI-2) mediante experimentos de competencia in vivo con cepas de Salmonella de tipo silvestre, con o sin coinfección con Eimeria. Pollos libres de patógenos específicos de un día de edad se inocularon por vía oral con un inóculo falso o con 4 × 102 de un coctel de ooquistes de Eimeria que incluyó Eimeria tenella, Eimeria acervulina, Eimeria maxima y Eimeria mitis. A los seis días de edad, se les administró a las aves administró por vía oral una proporción 1: 1 de Salmonella Typhimurium de tipo silvestre o tipo mutante que es deficiente de tetrationato reductasa, SPI-1 o SPI-2 (108 unidades formadoras de colonias/ave). Se recolectaron ciegos, hígados y pernas a los tres, siete, catorce y 42 días después de la infección por Salmonella, para bacteriología. La inflamación intestinal se calificó por histología. Se observó inflamación intestinal significativamente mayor en los grupos de desafío en comparación con el control. Sin embargo, no hubo diferencias significativas en las puntuaciones de inflamación intestinal entre los grupos coinfectados con Eimeria spp. y Salmonella Typhimurium y las aves infectadas con Salmonella por si sola y la coinfección con Eimeria no aumentó la prevalencia o abundancia de Salmonella. A diferencia de los estudios en ratones, la tetrationato reductasa no mejoró la colonización cecal de Salmonella Typhimurium o la diseminación sistémica en pollos. Las islas de patogenicidad SPI-1 y SPI-2 jugaron un papel importante en la diseminación de Salmonella y en la colonización cecal en pollos, respectivamente.

Identification of a Short DNA Bar Code in the 18S rDNA for Improved Differentiation of Common Eimeria Species Infecting Chickens.

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.

A case of emphysematous cystitis and bladder rupture.

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.

Effect of Pullet Vaccination on Development and Longevity of Immunity.

Avian respiratory disease causes significant economic losses in commercial poultry. Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). Often the interval between vaccinations is only a matter of weeks, yet it is unknown whether the development of immunity and protection against challenge when vaccines are given in short succession occurs in these birds, something known as viral interference. Our objective was to determine whether serially administered, live attenuated vaccines against IBV, NDV, and ILTV influence the development and longevity of immunity and protection against challenge in long-lived birds. Based on a typical pullet vaccination program, specific-pathogen-free white leghorns were administered multiple live attenuated vaccines against IBV, NDV, and ILTV until 16 weeks of age (WOA), after which certain groups were challenged with IBV, NDV, or ILTV at 20, 24, 28, 32, and 36 WOA. Five days post-challenge, viral load, clinical signs, ciliostasis, tracheal histopathology, and antibody titers in serum and tears were evaluated. We demonstrate that pullets serially administered live attenuated vaccines against IBV, NDV, and ILTV were protected against homologous challenge with IBV, NDV, or ILTV for at least 36 weeks, and conclude that the interval between vaccinations used in this study (at least 2 weeks) did not interfere with protection. This information is important because it shows that a typical pullet vaccination program consisting of serially administered live attenuated vaccines against multiple respiratory pathogens can result in the development of protective immunity against each disease agent.

Comparison of the application parameters of coccidia vaccines by gel and spray.

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 Timing and Frequency of Infectious Complications after Radical Cystectomy: An Opportunity for Rescue Antibiotic Treatment.

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 review was performed of all patients undergoing radical cystectomy in the 2011 to 2013 American College of Surgeons NSQIP® database and 100 consecutive patients from our institution. We evaluated the rates and timing of postoperative urinary tract infection and sepsis as well as associations with hospital readmissions. Specific culture data and treatment interventions were assessed and an institution specific urinary tract infection antibiogram was created. RESULTS: Among the 3,495 patients identified in the NSQIP database the 30-day rates of urinary tract infection and sepsis were 9.5% and 9.4%, respectively, and median days to urinary tract infection and sepsis were 15 and 13. Median length of stay after radical cystectomy was 10.4 days. Overall 61.5% of urinary tract infections and 52.1% of sepsis episodes occurred after discharge home. At our institution the rates of urinary tract infection and sepsis were 15% and 9%, and occurred at a median of 14 and 18 days, respectively. The 30-day readmission rate was 21%, with 10 readmissions for infections including 7 for urinary tract infection and 5 for bacteremia. We identified 9 patients with positive urine or blood cultures for yeast requiring antifungal therapy. Of the urinary tract infections 88% were sensitive to oral agents and 79% were sensitive to nitrofurantoin or ciprofloxacin. CONCLUSIONS: The timing of urinary tract infections/sepsis after radical cystectomy is predictable on the national and institutional level. At our hospital, cultured organisms are likely to respond to well tolerated oral therapies. This information can be used to implement an outpatient antibiotic protocol to prevent infectious complications after radical cystectomy.

Biological and molecular characterization of ArkGA: A novel Arkansas serotype vaccine that is highly attenuated, efficacious, and protective against homologous challenge.

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.

Transversus Abdominis Plane Blockade as Part of a Multimodal Postoperative Analgesia Plan in Patients Undergoing Radical Cystectomy.

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 < 0.001) and 62 vs 203 mg (p = 0.001), respectively. The ERAS cohort had fewer days to flatus (3 vs. 4, p < 0.001) and fewer days to bowel movement (4 vs. 5, p < 0.001). Median LOS was shorter in the ERAS cohort (7 vs. 8.5d, p = 0.001). There were no differences in complications or readmission rates between the two cohorts. CONCLUSIONS: TAP blockade as part of an ERAS multi-modal pain plan is associated with low narcotic usage, and significant improvement in time to flatus, BM, and LOS compared to traditional post-RC pain management.

Evaluation of a coccidia vaccine using spray and gel applications.

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.

Automated Extraction of Grade, Stage, and Quality Information From Transurethral Resection of Bladder Tumor Pathology Reports Using Natural Language Processing.

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.

Importance of identification of prostatic adenocarcinoma in urine cytology.

BACKGROUND: Prostate carcinoma (PCa) occasionally involves the urethra and/or bladder. In these cases, PCa cells may be detected in urine. The purpose of this study was to describe the salient cytomorphologic, immunocytochemical, and epidemiologic features of PCa cells detected in urine cytology slides via a retrospective case series review. MATERIALS AND METHODS: We retrospectively identified 28 cases with urine cytology either suspicious or positive for PCa. Clinical and histopathologic data were reviewed. RESULTS: We identified 23 prostatic acinar adenocarcinomas (PAAs) and 5 prostatic adenocarcinomas with ductal features (PDAs). Urine cytology was the first evidence of disease in 6 (26%) patients with PAA and in 4 (80%) of the patients with PDA. In patients with PAA, 17 had a previous history of PAA, with positive urine cytology in the setting of disease recurrence or persistence within the bladder or urethra. The PAA in urine presented as single or small clusters of atypical cuboidal glandular cells with large, eccentric, round, or oval uniform nuclei containing conspicuous nucleoli, and scant to moderate delicate or granular cytoplasm, whereas the PDA presented as atypical columnar glandular cells in flat nests or 3-dimensional clusters, and with prominent nucleoli. CONCLUSIONS: Using standard urine cytology, we were able to detect PCa cells in the urine. Although rare, PCa was first diagnosed by urine cytology in select cases, with a higher frequency in patients with PDA. Clinicians should be aware that PCa cells can be identified by urine cytology as this can lead to an earlier diagnosis and treatment.

Venous thromboembolism after nephrectomy: incidence, timing and associated risk factors from a national multi-institutional database.

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. METHODS: 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. RESULTS: 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 < 0.001). Median times to DVT and PE were 8.5 and 6 days, respectively, with 53.3% of DVTs and 63.1% of PEs occurring prior to discharge. CONCLUSIONS: The overall rate of VTE after nephrectomy is low, occurs roughly one week after surgery, and is associated with longer hospital stays. Certain patient factors, open surgical approach, and longer operative times were associated with higher odds of post-operative VTE; these patients may benefit from more aggressive prophylaxis.

Minimum Infectious Dose Determination of the Arkansas Delmarva Poultry Industry Infectious Bronchitis Virus Vaccine Delivered by Hatchery Spray Cabinet.

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.

Insights from molecular structure predictions of the infectious bronchitis virus S1 spike glycoprotein.

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.

Generation of Avian Induced Pluripotent Stem Cells.

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.

Evaluating Protection Against Infectious Bronchitis Virus by Clinical Signs, Ciliostasis, Challenge Virus Detection, and Histopathology.

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.