Mitigation of False Layer Syndrome Through Maternal Antibodies Against Infectious Bronchitis Virus.

The relationship between passive immunity and the development of false layer syndrome (FLS) and its associated lesions was investigated in this study by comparing the long-term reproductive effects of an infectious bronchitis virus (IBV) DMV/1639 wild-type strain and the GA08 vaccine in birds with and without maternal antibodies. There was a clear protective effect provided by maternal antibodies against both the early vaccination and challenge. It was also observed that vaccination at an early age, in the absence of maternal antibodies, can induce reproductive issues, such as reduced egg production and FLS-associated lesions (e.g., cystic oviduct and egg yolk coelomitis). This might indicate that maternal antibodies and the timing of IBV infection are more important in the generation of FLS than the IBV strain type.

Mitigación del síndrome de la falsa ponedora mediante anticuerpos maternos contra el virus de la bronquitis infecciosa. En este estudio se investigó la relación entre la inmunidad pasiva y el desarrollo del síndrome de la falsa ponedora (FLS) y sus lesiones asociadas comparando los efectos reproductivos a largo plazo de una cepa de tipo silvestre DMV/1639 del virus de la bronquitis infecciosa (IBV) y la cepa vacunal GA08, en aves con y sin anticuerpos maternos. Hubo un claro efecto protector proporcionado por los anticuerpos maternos tanto contra la vacunación temprana como contra el desafío. También se observó que la vacunación a una edad temprana, en ausencia de anticuerpos maternos, puede inducir problemas reproductivos, como una reducción de la producción de huevo y lesiones asociadas al síndrome de la falsa ponedora (p. ej., oviducto quístico y celomitis de yema de huevo). Esto podría indicar que los anticuerpos maternos y el momento de la infección por el virus de la bronquitis infecciosa son más importantes en la generación del síndrome de la falsa ponedora que el tipo de cepa del virus de la bronquitis infecciosa.

Changes in Physiological Indices, Amino Acids, and Volatile Compounds in Vitis vinifera L. cv. Pinot Noir under UV-B Radiation and Water Deficit Conditions.

UV-B radiation and water deficit can challenge Pinot noir growth and fruit quality. The aim of this work is to determine the effects of UV-B and water deficit on the physiological indices, amino acids, and volatile compounds of Pinot noir vine and fruit. The results showed that both individual and combined treatments caused a decrease in the leaf SPAD, with the largest amplitude being observed in the combined treatment. Water deficit also decreased the leaf water potential and increased the juice δ13C‱ at harvest, which was the opposite of the latter under UV-B radiation. Interestingly, most of the physiological indices under combined stresses did not show significant changes compared with that under no UV-B and the well-watered control treatment. Moreover, the concentrations of amino acids and volatile compounds in the berries were determined at harvest. The amino acid contents were significantly increased by the combined treatment, particularly proline (Pro), aspartate (Arg), alanine (Ala), and threonine (Thr). There were slight increases in volatile compounds. This research substantially contributed to improve our scientific understanding of UV-B and water deficit responses in an important commercial species. In addition, it highlighted some future research to produce high-quality wines with the anticipated specific characteristics.

UV-B Radiation Induced the Changes in the Amount of Amino Acids, Phenolics and Aroma Compounds in Vitis vinifera cv. Pinot Noir Berry under Field Conditions.

High UV-B radiation can challenge Pinot noir growth in the wine-making region of the Southern Hemisphere. The aim of this work was to determine UV-B effects on amino acids, phenolic composition and aroma compounds of Pinot noir fruit. Sunlight exposure with or without UV-B did not affect fruit production capacity, °Brix and total amino acids in the vineyard over the two years. This research reported increased contents of skin anthocyanin and skin total phenolics in berry skins under UV-B. The research showed that there were no changes in C6 compounds. Some monoterpenes concentrations were decreased by UV-B. The information also indicated how important leaf canopy management was for vineyard management. Therefore, UV radiation potentially affected fruit ripeness and crop load, and even stimulated the accumulation of phenolic compounds that may affect Pinot noir quality. This research reported that canopy management (UV-B exposure) may be a good way for vineyard management to increase the accumulation of anthocyanins and tannins in berry skins.

Perioperative Improvement in Pulmonary Function in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: The objective of this study was to compare serial changes in pulmonary function in contemporary infants with congenital diaphragmatic hernia managed with a gentle ventilation approach. STUDY DESIGN: Observational cohort, single-center study of infants ≥350/7 weeks gestation at delivery with congenital diaphragmatic hernia. Functional residual capacity (FRC), passive respiratory compliance, and passive respiratory resistance were measured presurgical and postsurgical repair and within 2 weeks of discharge. A 1-way analysis of variance for repeated measures was used to evaluate the change in FRC, passive respiratory compliance, and passive respiratory resistance over these repeated measures. RESULTS: Twenty-eight infants were included in the analysis with a mean gestational age of 38.3 weeks and birth weight of 3139 g. We found a significant increase in FRC across the 3 time points (mean in mL/kg [SD]: 10.9 [3.6] to 18.5 [5.2] to 24.2 [4.4]; P < .0001). There was also a significant increase in passive respiratory compliance and decrease in passive respiratory resistance. In contrast to a previous report, there were survivors in the current cohort with a preoperative FRC of <9 mL/kg. The mean FRC measured at discharge was in the range considered within normal limits. Sixteen infants had prenatal measurements of the lung-to-head ratio, but there was no relationship between the lung-to-head ratio and preoperative or postoperative FRC measurements. CONCLUSIONS: Infants with congenital diaphragmatic hernia demonstrate significant increases in FRC and improvements in respiratory mechanics measured preoperatively and postoperatively and at discharge. We speculate these improvements are due to the surgical resolution of the mechanical obstruction to lung recruitment and that after achieving preoperative stability, repair should not be delayed given these demonstrable postoperative improvements.

Cells Gone Wild: A Case Report on Missed Acute Leukemia and Subsequent Disseminated Intravascular Coagulation in the Emergency Department.

INTRODUCTION: Emergency physicians must maintain a broad differential when seeing patients in the emergency department (ED). Occasionally, a patient may have an undiagnosed, life-threatening medical condition not related to the presenting chief complaint. It is imperative to review all ordered laboratory tests and any available previous laboratory values to assess for any abnormalities that may warrant further evaluation. CASE REPORT: This case report is regarding the missed diagnosis of acute leukemia and subsequent disseminated intravascular coagulation in a 27-year-old male who presented to multiple EDs with the unrelated chief complaint of finger ring entrapment. This patient ultimately succumbed to his illness. CONCLUSION: When evaluating patients in the ED, it is important to review any prior available test results for abnormalities, even if the results do not specifically correlate with the chief complaint. Emergency physicians must remain vigilant to avoid missing a critical diagnosis.

Let's Talk about Dex: When do the Benefits of Dexamethasone for Prevention of Bronchopulmonary Dysplasia Outweigh the Risks?

Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity and carries increased respiratory morbidity into childhood and adulthood. Systemic administration of dexamethasone during the preterm period has been shown to decrease the incidence of BPD in this population. However, enthusiasm about its use has been tempered by early evidence that suggested potential adverse neurodevelopmental outcomes. More recent studies suggest that the timing, dosing, and duration of therapy may have a significant impact on the safety and efficacy of dexamethasone administration and that side effects and harms may be minimized if its use is appropriately targeted. Focusing on studies published since the 2010s American Academy of Pediatrics (AAP) statement on dexamethasone, this review seeks to examine the evidence from recent clinical trials to present the current state of knowledge regarding the systemic dexamethasone administration to prevent BPD in extremely premature infants and how dose, duration, and timing might impact its safety and efficacy in this vulnerable population.

Infection with IBV DMV/1639 at a Young Age Leads to Increased Incidence of Cystic Oviduct Formation Associated with False Layer Syndrome.

Infectious bronchitis virus (IBV) is an avian coronavirus that causes respiratory disease but can affect the reproductive tract of laying-type chickens. If infection occurs in pullets, false layer syndrome, which is characterized by the development of large, fluid-filled cystic oviducts, can occur. Recently, IBV strain DMV/1639 has been detected in parts of Canada and the U.S., where false layer syndrome has occurred, though it is not clear if IBV is the sole cause or if age at infection is an influencing variable. Our study investigates the role and timing of IBV infection on the development of false layer syndrome, using the IBV types DMV/1639 and Massachusetts (Mass). Six groups of 120 SPF chickens were challenged at either three, seven, or fourteen days of age, using either DMV/1639 or Mass IBV. Cystic oviducts were seen in all the challenged groups, and the pullets challenged at 14 days of age had fewer cystic oviducts than pullets challenged at 3 or 7 days of age. The highest percentage of severe histology lesion scores were seen in the 3-day challenge groups. The data collected in this experiment confirm that IBV DMV/1639 causes cystic oviducts and indicate that age at infection plays a role in the pathogenesis of false layer syndrome.

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.

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.

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.

Trajectories of Lung Function in Infants and Children: Setting a Course for Lifelong Lung Health.

For healthy individuals, it is increasingly accepted that lung function follows along an individual percentile established early in life and that the level of maximal function reached as a young adult can affect the subsequent development of lung disease that occurs with the normal aging process. This emphasizes the need to maximize early lung function. The trajectories of lung function are at least partially established by perinatal factors, including prematurity and in utero exposures (tobacco exposure, nutrition, inflammation, etc), although they can also be affected by a variety of additional factors and exposures throughout the life span. Whether lung function trajectories can be impacted or reset if established under suboptimal conditions is an unanswered question, offering new avenues for research. In this review, we will summarize important articles outlining lung function trajectories and linking pediatric lung function tests to adult lung function tests decades later. We will focus on perinatal factors and outline progress and opportunities for further investigation into the potential ability to reset trajectories to impact long-term lung health.

Identification of Differential Tumor Subtypes of T1 Bladder Cancer.

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-Guérin (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-Guérin treatment. We validated the subtypes and describe a single-patient classifier.

The Evolution of Flavonoid Biosynthesis: A Bryophyte Perspective.

The flavonoid pathway is one of the best characterized specialized metabolite pathways of plants. In angiosperms, the flavonoids have varied roles in assisting with tolerance to abiotic stress and are also key for signaling to pollinators and seed dispersal agents. The pathway is thought to be specific to land plants and to have arisen during the period of land colonization around 550-470 million years ago. In this review we consider current knowledge of the flavonoid pathway in the bryophytes, consisting of the liverworts, hornworts, and mosses. The pathway is less characterized for bryophytes than angiosperms, and the first genetic and molecular studies on bryophytes are finding both commonalities and significant differences in flavonoid biosynthesis and pathway regulation between angiosperms and bryophytes. This includes biosynthetic pathway branches specific to each plant group and the apparent complete absence of flavonoids from the hornworts.

Molecular mechanisms of curcumin and its analogs in colon cancer prevention and treatment.

Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. Curcumin analogues like IND-4, FLLL, GO-Y030 and C086 have demonstrated to produce greater cytotoxicity when experimentally studied and study results from many have been suggested to be the same. Combination of curcumin with therapeutic cancer agents like tolfenamic acid, 5-fluorouracil, resveratrol and dasatinib showed improved cytotoxicity and chemotherapeutic effect. The results propose that employment of curcumin with novel drug delivery systems like liposome, micelles and nanoparticle have been performed which could improve the therapeutic efficacy against colon cancer. The present review highlights the mechanism of action, synergistic effect and novel delivery methods to improve the therapeutic potential of curcumin.

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.

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.

T1 bladder cancer: current considerations for diagnosis and management.

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.

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.

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms.

Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anticancer activity against various types of cancers and high-safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27; however, these compounds did not show any activity on pSTAT3 phosphorylation at IC50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3.