Protective influence of supplementary betaine against heat stress by regulating intestinal oxidative status and microbiota composition in broiler chickens.

To assess the impact of supplementing betaine (BT) under heat stress (HS) conditions on broiler performance and intestinal health from 21 to 42 days of age, a total of 150 male Ross 308 broilers were indiscriminately allotted to 3 treatments with 10 replications of 5 birds each. The control (CON) group was given a basal ration and accommodated at a thermoneutral condition (22 ± 1 °C), whereas the HS and HS + BT groups were raised under cyclic HS (33 ± 1 °C for 8 h and 22 ± 1 °C for 16 h per day) and received the basal ration without or with 1000 mg/kg BT, respectively. The HS reduced average daily gain (ADG); average daily feed intake; villus height (VH); VH to crypt depth (CD) ratio (VCR); activities of trypsin, lipase, glutathione peroxidase (GPX), and catalase; and enumeration of Lactobacillus and Bifidobacterium (P < 0.05) and augmented feed conversion ratio (FCR), CD, malondialdehyde (MDA) accumulation, and enumeration of Escherichia coli, Clostridium, and coliforms (P < 0.05). Conversely, BT supplementation heightened ADG, VH, VCR, trypsin activity, GPX activity, and populations of Lactobacillus and Bifidobacterium (P < 0.05) and lowered FCR, MDA accumulation, and Clostridium population (P < 0.05). Furthermore, the FCR value, trypsin and GPX activities, MDA content, and Bifidobacterium and Clostridium populations in the HS + BT group were nearly equivalent to those in the CON group. To conclude, feeding BT under HS conditions could improve broiler performance through improving intestinal health by specifically mitigating oxidative damage and enhancing the colonization of beneficial bacteria.

Effect of dietary electrolyte balance and arginine to lysine ratio on hematological, antioxidant and immunological traits in dual-purpose breeding hens under cyclic heat stress condition.

A total of 245 hens and 35 cocks (32 weeks age) were assigned to seven treatment groups (five replicates with seven hens and one cock) to investigate the effect of dietary electrolyte balance (DEB) and arginine to lysine ratio (Arg/Lys) on birds' physiological and biochemical traits under cyclic heat stress (CHS) condition. Birds were housed in an environmentally controlled facility having four sectors. The first group (positive control, PC) was kept under thermoneutral conditions and fed diet with DEB of 180 mEq and Arg/Lys of 1.25, whereas the other six treatments were kept in the second sector under CHS and fed diet with DEB and Arg/Lys equal to: 180 mEq and 1.25 (negative control, NC); 250 mEq and 1.25; 320 mEq and 1.25; 180 mEq and 1.37; 250 mEq and 1.37; 320 mEq and 1.37, respectively. Hens on NC group had significantly decreased red blood cells (RBCs), white blood cells (WBCs) and its fractions. The groups fed different DEB and Arg/Lys in diet significantly enhanced the blood parameters and plasma lipid profile compared NC group. Hens under CHS fed on 250 and 320 DEB with 1.37 Arg/Lys recorded the lowest concentration of low-density lipoprotein (LDL) compared with the other groups. Triiodothyronine (T3) activity was not differed among groups, while T4 activity in layer exposed to CHS (NC group) recorded the highest activity compared to PC. From findings, it can be concluded that laying hens fed a diet having DEB 250 mEq with 1.37 Arg/Lys could be successfully applied to counteract the adverse effect of CHS and to improve blood hematological and biochemical traits, antioxidants, and immunity response.

Growth performance, plasma metabolites, meat quality, and meat and lipid health indices of New Zealand White rabbits as affected by dietary dried tomato pomace powder supplementation during the summer season.

One hundred and twenty New Zealand White rabbits (NZW) (5-week-old; 735.27 ± 27.23 g) were kept in an open-sided house during the summer season. The experiment aims to evaluate the impacts of dried tomato pomace powder (DTPP) supplementation on rabbits' performance, blood metabolites, carcass traits, meat quality, and lipid and health indices of NZW rabbits during 5-13 weeks of age. The four treatments were a standard rabbit feed (control) and the control diet supplemented with 0.5, 1.0, and 1.5% DTPP, respectively. Rabbits fed a diet containing 1.5% DTPP showed the highest growth rate through weeks 9-13 of age despite having the lowest feed intake spanning 5-13 weeks. The best feed conversion ratio (FCR) was recorded in rabbits fed with 1.5% DTPP-supplemented diet for 5-13 weeks. Diets supplemented with 0.5 or 1.0% DTPP enhanced markedly dressing %, total edible flesh, saturated (SFAs), monounsaturated (MUFAs), and polyunsaturated fatty acid (PUFAs) contents, as well as the ∑n - 6/∑n - 3 ratio and the total n - 6 of meat. Dietary supplementation with DTPP decreased kidney, abdominal, and back fat. Diets supplemented with DTTP decreased total cholesterol, triglycerides, and very low-density lipoprotein (vLDL) concentrations. The greatest levels of linoleic acid, arachidonic and water-holding capacity in meat were observed in rabbits fed 1.5% DTPP-supplemented diets. Diets containing 1 and 1.5% DTPP improved meats' atherogenic and thrombogenic indices, meat lipid quality desired fatty acids/undesired fatty acids ratio, and meat health index. Conclusively, DTPP up to 1.5% maintained the growth performance of rabbits, boosted meat quality through increasing vitamin E, reduced fat deposition, modified fatty acid composition, and improved atherogenic, thrombogenic, and hypocholesterolemic indices of rabbit meat.

Dietary flaxseed cake influences on performance, quality, and sensory attributes of eggs, serum, and egg trace minerals of laying hens.

Nowadays, there is a global shortage in feed supply for animal nutrition; however, there are a considerable amount of agro-industrial co- and by-products that may offer a reasonable solution. Flaxseed cake (FSC) is a by-product of flaxseed for oil extraction rich in n-3 α-linolenic acid (ALA). Thus, the dietary inclusion of FSC on laying performance, egg quality, and serum and egg trace elements (Se, Zn, and Fe) was evaluated using Hisex White hens. The hens were distributed to three equal experimental treatments and provided diets including 0%, 5%, or 10% FSC from 48 to 58 weeks of age. Findings clarified that up to 10% FSC in the laying hen diet had no detrimental effect on laying rate, egg mass, and feed utilization. It was found that FSC resulted in a valuable source of protein, energy, macro- (Ca and P), micro- (Se, Zn and Fe) elements, and essential amino acids, with arginine being the highest. Dietary FSC did not negatively influence the egg quality traits, as well as egg sensory attributes. Including 5% or 10% FSC in diet did not significantly affect serum total protein and renal function in terms of creatinine, uric acid, and uric acid-to-creatinine ratio. Different FSC levels did not influence the chemical composition of eggs and trace elements in serum and eggs. It could be concluded that FSC is a valuable feedstuff that can provide a good source of energy, protein, amino acids, and macro- and micro-elements for hens' nutrition. The inclusion of up to 10% of FSC in hens diet did not adversely influence egg laying performance, egg quality of both fresh and stored eggs, sensory attributes, and nutritional composition, as well as Se, Zn, and Fe in serum and eggs due to balanced nutrient profile of FSC.

Rice gluten meal as a substitute for soybean meal in the diets for growing rabbits.

The impacts of different dietary levels of rice gluten meal (RGM) on growth performance, digestibility, carcass characteristics, and blood traits of growing New Zealand White (NZW) rabbits were studied. One hundred and twenty, 6 weeks old weaned male rabbits (body weight; 682 [g] ± 23) were randomly allotted into four groups. The control diet contained 160 [g/kg] soybean meal (SBM), while the other three diets were obtained by replacing 40, 80, and 120 [g/kg] SBM with RGM (RGM40, RGM80, and RGM120, respectively). The results showed that RGM contained higher levels of dry matter (DM), crude protein (CP), ether extract (EE), ash, and gross energy than SBM. RGM contained a high level of arginine followed by leucine and valine as essential amino acids and high levels of glutamic, aspartic acid, and alanine as non-essential amino acids. The obtained results showed that the final body weight of rabbits fed diets containing 40, 80, and 120 [g/kg] RGM was higher than those fed the control diet. The daily weight gain of rabbits fed RGM diets increased (p < 0.05) by 10.50%, 6.50%, and 10.00%, respectively, compared to the control group. Rabbits fed RGM80 showed the highest (p < 0.05) digestibility of DM, organic matter (OM), EE, neutral detergent fibre (NDF), and acid detergent fibre (ADF) compared to the other tested levels. Rabbits fed RGM120 had the highest (p < 0.05) digestible energy (DE) and digestible crude protein (DCP) values. RGM inclusion levels of 40 and 80 [g/kg] increased (p < 0.05) plasma total protein and albumin compared to the control group. Rabbits fed a diet containing RGM40 had the highest (p < 0.05) globulin level. The highest (p < 0.05) plasma urea concentration level was measured in the rabbit group fed the RGM120 diet. Conclusively, RGM could be a valuable ingredient for growing rabbits, as at all the tested levels improved growth performance, digestibility, and nutritional values.

Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.

TP53 genetic polymorphisms and susceptibility to cervical cancer in Bangladeshi women: a case-control study.

Pharmacogenetic study of TP53 gene polymorphisms has not been conducted extensively in cervical cancer. The aim of this study was to assesses the TP53 codon 72 and codon 47 polymorphisms and their relation to cervical cancer risk in Bangladeshi women. 134 cervical cancer patients and 102 age matched healthy controls were included from two institutions in Bangladesh. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping two TP53 single nucleotide polymorphisms (codon 72 and codon 47) in patients and controls. The results indicate that the TP53 Arg/Pro heterozygosity (adjusted OR 2.32, 95% CI 1.28-4.34, p = 0.01), Pro/Pro mutant homozygosity (adjusted OR 4.15, 95% CI 1.75-9.86, p = 0.001), along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR 2.83, 95% CI 1.61-4.97, p < 0.001) significantly increases the risk of cervical cancer. Moreover, the cervical cancer patients with a first-degree relative cancer patient possesses 4.45 folds more risk (p = 0.019) of carrying a proline allele in codon 72 of the TP53 gene compared to those patients who do not have any first-degree relative with cancer. Finally, polymorphism in the codon 47 of the TP53 gene did not significantly increase the risk of cervical cancer in Bangladeshi women. To conclude, this is the first study to identify that polymorphism in the TP53 codon 72 significantly increases the risk of cervical cancer in a female population in Bangladesh.

Site of extranodal metastasis impacts survival in patients with testicular germ cell tumors.

BACKGROUND: Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS: Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS: Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71. CONCLUSIONS: The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.

Is cytoreductive nephrectomy relevant in the immunotherapy era?

PURPOSE OF REVIEW: The recent approval of immune checkpoint inhibitors (ICI) revolutionized the treatment paradigm for metastatic renal cell carcinoma (mRCC). However, the role of cytoreductive nephrectomy is not well defined in this setting. Here, we review the contemporary role and timing of cytoreductive nephrectomy for advanced RCC in the era of immunotherapy. RECENT FINDINGS: Evidence concerning combination systemic therapy and cytoreductive nephrectomy in the multimodal management of mRCC is primarily limited to studies conducted in the targeted therapy era. The oncologic role of cytoreductive nephrectomy in the setting of ICI remains largely undefined and is supported primarily by case reports. Nonetheless, patient selection for cytoreductive nephrectomy is paramount, and appropriate candidacy in the ICI era will likely be refined as increasing evidence emerges. Until then, a cautious balance between perceived oncologic benefit and risks of intervention must be exercised. Several trials are ongoing to help shed light on patient selection, technical feasibility, and optimal timing of cytoreductive nephrectomy in the immunotherapy era. SUMMARY: Although the role and timing for cytoreductive nephrectomy remain to be further elucidated in the immunotherapy era, patient selection remains critical for treatment planning. Further studies are urgently needed to better define the role of cytoreductive nephrectomy in this setting.

Sex differences in upper tract urothelial carcinomas.

PURPOSE OF REVIEW: To evaluate contemporary sex-specific differences in upper tract urothelial carcinoma (UTUC) by reviewing diagnostic considerations, clinicopathologic features, oncologic outcomes, environmental exposures, and regional variation in UTUC by sex. RECENT FINDINGS: Although some contemporary studies implicate sex-based differences in UTUC, the literature concerning the effect of sex on clinicopathologic features and oncologic outcomes in UTUC reveals mixed findings. Factors accounting for the time to diagnosis in UTUC seem to differ between men and women. The epidemiology and outcomes of UTUC are largely influenced by geographic variation in the disease, which may be due to differences in exposure to environmental risk factors. Sex-based variations and potential differences in disease biology remain to be elucidated. SUMMARY: A global consensus on the effect of sex on clinicopathologic characteristics and oncologic outcomes in UTUC has not been established definitively. Review of this topic does, however, shed light on important considerations given differences in the time to diagnosis, risk factors, and regional variation by sex. Further studies evaluating genetic, anatomic, physiologic, and socioeconomic differences between men and women with UTUC may provide further insight into understanding the effect of sex in UTUC.

Genetics of testicular germ cell tumors.

PURPOSE OF REVIEW: Understanding the molecular basis underlying testicular germ cell tumors (TGCTs) may help improve patient outcomes, particularly for patients with poorer risk or chemoresistant disease. Here, we review the major contemporary advances in elucidating TGCT genetics by discussing patterns of TGCT inheritance, recent genomic and transcriptomic discoveries in TGCT, and the role of genetics in predicting therapeutic resistance and in guiding treatment. RECENT FINDINGS: In the absence of a major high-penetrance TGCT susceptibility gene, inheritance is likely driven by a complex polygenic model with considerable variation. The most common genomic alterations found in TGCTs include gains in chromosome 12p and mutations in KIT, KRAS, and NRAS, particularly in seminomas. Sensitivity to cisplatin-based chemotherapy likely relies on intact TP53, reciprocal loss of heterozygosity, and high mitochondrial priming. Targetable mutations are uncommon in TGCTs, however, posing a challenge for the development of effective personalized therapies. Consistent with the characteristically low tumor mutational burden, immune checkpoint inhibitors do not appear to be effective for most TGCTs. SUMMARY: Refinements in next-generation sequencing techniques over the last few years have enabled considerable advances in elucidating the genomic, transcriptomic, and epigenetic landscape of TGCTs. Future efforts focused on developing novel treatment modalities are needed.

Methods for simulating nutritional requirement and response studies with all organisms to increase research efficiency.

Nutritional requirements and responses of all organisms are estimated using various models representing the response to different dietary levels of the nutrient in question. To help nutritionists design experiments for estimating responses and requirements, we developed a simulation workbook using Microsoft Excel. The objective of the present study was to demonstrate the influence of different numbers of nutrient levels, ranges of nutrient levels and replications per nutrient level on the estimates of requirements based on common nutritional response models. The user provides estimates of the shape of the response curve, requirements and other parameters and observation to observation variation. The Excel workbook then produces 1-1000 randomly simulated responses based on the given response curve and estimates the standard errors of the requirement (and other parameters) from different models as an indication of the expected power of the experiment. Interpretations are based on the assumption that the smaller the standard error of the requirement, the more powerful the experiment. The user can see the potential effects of using one or more subjects, different nutrient levels, etc., on the expected outcome of future experiments. From a theoretical perspective, each organism should have some enzyme-catalysed reaction whose rate is limited by the availability of some limiting nutrient. The response to the limiting nutrient should therefore be similar to enzyme kinetics. In conclusion, the workbook eliminates some of the guesswork involved in designing experiments and determining the minimum number of subjects needed to achieve desired outcomes.

Broadband optical transparency in plasmonic nanocomposite polymer films via exciton-plasmon energy transfer.

Inherent absorptive losses affect the performance of all plasmonic devices, limiting their fascinating applications in the visible range. Here, we report on the enhanced optical transparency obtained as a result of the broadband mitigation of optical losses in nanocomposite polymeric films, embedding core-shell quantum dots (CdSe@ZnS QDs) and gold nanoparticles (Au-NPs). Exciton-plasmon coupling enables non-radiative energy transfer processes from QDs to metal NPs, resulting in gain induced transparency of the hybrid flexible systems. Experimental evidences, such as fluorescence quenching and modifications of fluorescence lifetimes confirm the presence of this strong coupling between plexcitonic elements. Measures performed by means of an ultra-fast broadband pump-probe setup demonstrate loss compensation of gold NPs dispersed in plastic network in presence of gain. Furthermore, we compare two films containing different concentrations of gold NPs and same amount of QDs, to investigate the role of acceptor concentration (Au-NPs) in order to promote an effective and efficient energy transfer mechanism. Gain induced transparency in bulk systems represents a promising path towards the realization of loss compensated plasmonic devices.

Population Dynamics of Released Potato Psyllids and their Bacteriliferous Status in Relation to Zebra Chip Incidence in Caged Field Plots.

Potato psyllids vector 'Candidatus Liberibacter solanacearum' (Lso), the putative causal agent of potato zebra chip (ZC). Currently, sticky traps are the primary psyllid monitoring tools used by growers for making management decisions. However, the reliability of sticky traps in predicting psyllid numbers in potato fields has always been questioned. In 2013 and 2014, experiments were conducted in covered field plots at the Texas A&M AgriLife Research Station at Bushland to investigate the relationships among initial psyllid numbers, psyllids captured on sticky traps and their Lso status, and zebra chip incidence. Three densities of Lso-positive psyllids (5, 15, or 30/cage) were released under 2-week-old potato canopies with four replications in plot sizes of 7.6 to 9 m by 5 rows. Psyllids were released under the first plant in the center row and monitored weekly with a yellow sticky trap from the opposite end. Number of plants with zebra chip symptoms also was counted weekly beginning one month after infestation with psyllids. The total number of psyllids captured on sticky traps and disease incidence levels generally corresponded to the levels of psyllid density treatments (5 < 15 < 30), but the differences became more apparent toward the end of the experiments. Psyllid numbers in the different density treatments fluctuated more or less in synchrony over time, which appeared to reflect periodic emergence of new generations of psyllids. Initially, all captured psyllids tested positive for Lso. However, the proportions of psyllids testing positive declined dramatically after a few weeks, which suggested that the new generations of psyllids were devoid of Lso. Over all, less than 50% of captured psyllids tested positive for the pathogen. The decline in proportions of psyllids testing positive for Lso following successive generations has significant relevance to field situations and may partly explain why there are generally low percentages of Lso-positive psyllids under field conditions.

Active Surveillance is Superior to Radical Nephrectomy and Equivalent to Partial Nephrectomy for Preserving Renal Function in Patients with Small Renal Masses: Results from the DISSRM Registry.

PURPOSE: We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry. MATERIALS AND METHODS: Patients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival. RESULTS: A total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy and 14 undergoing cryoablation. Median tumor size was 2.2 cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs surveillance (-9.2 vs -0.5 ml/minute/1.73 m(2)) and for radical vs partial nephrectomy (-9.2 vs -1.9 ml/minute/1.73 m(2)) (p=0.001). No other groups differed significantly. On Kaplan-Meier analysis patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs those treated with partial nephrectomy (p=0.029), surveillance (p=0.007) and cryoablation (p=0.019). No other groups differed significantly. On multivariate analysis radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs surveillance 30.6, p=0.001). Neither partial nephrectomy (p=0.985) nor cryoablation (p=0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance. CONCLUSIONS: Patients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses.

Mixed low- and high-grade non-muscle-invasive bladder cancer: a histological subtype with favorable outcome.

OBJECTIVE: To determine whether heterogeneity of tumor grade affects the response to Bacillus Calmette-Guérin (BCG) treatment for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Patients with Ta or T1 NMBIC receiving a 6-week induction course of intravesical BCG therapy after transurethral resection were divided according to the tumor grade. Clinical and pathological variables were compared. Advanced intervention-free survival (AIFS), defined as duration of freedom from advanced intervention (including non-BCG intravesical agents or cystectomy) or metastasis, was plotted using Kaplan-Meier methods. The effect of grade on survival duration was assessed by multivariate Cox proportional hazards modeling. RESULTS: One hundred and fifty-three patients were identified: 17 with mixed low- and high-grade (MG) and 136 with pure high-grade (PHG) NMIBC. Demographic and additional pathologic variables were comparable between groups (p > 0.05). Five-year AIFS was 88.2% for MG patients, compared to 48.5% for PHG patients (p = 0.030 by log-rank test). On multivariate analysis, PHG was an independent risk factor for worse AIFS (HR 4.4, 95% CI 1.1-18.4, p = 0.040). Among patients failing to respond to primary BCG induction, who underwent a secondary induction of BCG with interferon, MG patients had better response than PHG patients (100 vs. 26.3%, p = 0.035). CONCLUSIONS: Mixed low- and high-grade NMIBC exhibits a significantly better response profile to intravesical BCG therapy compared to PHG NMIBC. The implications of these results are that less aggressive treatment strategies for this unique cancer entity may be needed and that there is a benefit to the reporting of tumor heterogeneity in transurethral resection of bladder tumor specimens.

Significance and Epidemiological Aspects of Late-Season Infections in the Management of Potato Zebra Chip.

Zebra chip (ZC) of potato is putatively caused by the fastidious, phloem-limited bacterium 'Candidatus Liberibacter solanacearum' (Lso), which is transmitted by the potato psyllid (Bactericera cockerelli). The disease, which significantly impacts both crop yield and quality, was first identified in the United States from south Texas in 2000. It reached epidemic levels in north Texas and certain production areas in Colorado, Nebraska, and New Mexico from 2004 to 2007 and it caused severe losses in fields in Oregon, Washington, and Idaho in 2011. The potato plant is susceptible to infection at all developmental stages, but disease management programs have focused on vector control through early and repeated insecticide applications, in an effort to minimize early to midseason infections which are most damaging. Growers often terminate spray programs 2 to 3 weeks prior to crop harvest due to lack of visible treatment effects on crop yield or quality. However, recent studies on vector transmission and host-pathogen interactions have revealed that late-season infections pose a significant, previously unrecognized, threat to crop quality. The pathogen can move from an infected leaf to tubers within 2 days; however, tubers infected less than 1 week before harvest will remain asymptomatic and the pathogen will be undetectable. When these tubers are placed into storage they are assumed to be disease free. However, Lso can continue to multiply in respiring tubers during storage, resulting in reduced tuber quality. Likewise, if plants become infected a few days before vines are killed, ZC can continue to develop in infected tubers before they are harvested. Perspectives on the significance of late-season infections and some of the more important issues associated with those infections are discussed.

Effects of Potato-Psyllid-Vectored 'Candidatus Liberibacter solanacearum' Infection on Potato Leaf and Stem Physiology.

The bacterium 'Candidatus Liberibacter solanacearum' is associated with zebra chip disease (ZC), a threat to potato production in North America and New Zealand. It is vectored by potato psyllids. Previous studies observed that 'Ca. L. solanacearum' infection causes potato tubers to undergo ZC-symptom-associated shifts in physiology, such as increased levels of amino acids, sugars, and phenolics. However, little is known about how 'Ca. L. solanacearum' infections caused by psyllid vector feeding may affect metabolism in potato foliage and stems. This study compared metabolism in potato plants fed upon by 'Ca. L. solanacearum'-positive psyllids with potato plants not exposed to psyllids. Foliar levels of asparagine, aspartic acid, glutamine, fructose, glucose, sucrose, a ferulic acid derivative, and quinic acid were lower in 'Ca. L. solanacearum'-inoculated than noninfected plants. However, foliar levels of proline, serine, four phenolic compounds, and most terpenoids were greater in 'Ca. L. solanacearum'-inoculated than noninfected plants. Upper stem levels of asparagine and aspartic acid, upper and lower stem levels of ellagitannins and most monoterpenoids, and lower stem level of sesquiterpenoids were greater in 'Ca. L. solanacearum'-inoculated than noninfected plants. These results suggest that many defense-related terpenoid compounds might increase in plants which had psyllids inoculate 'Ca. L. solanacearum'. This could impact progression and spread of ZC.

Phase II trial of intravesical nanoparticle albumin bound paclitaxel for the treatment of nonmuscle invasive urothelial carcinoma of the bladder after bacillus Calmette-Guérin treatment failure.

PURPOSE: Response rates to current second line intravesical therapies for recurrent nonmuscle invasive bladder cancer range between 10% and 30%. Nanoparticle albumin bound (nab-)paclitaxel has increased solubility and lower toxicity compared to other taxanes. Results of the phase I intravesical trial of this compound demonstrated minimal toxicity during dose escalation. We now report the results of a phase II trial to assess efficacy. MATERIALS AND METHODS: This study was an investigator initiated, single center, single arm, phase II trial investigating the use of nab-paclitaxel in patients with recurrent Tis, T1 and Ta urothelial carcinoma in whom at least 1 prior regimen of intravesical bacillus Calmette-Guérin failed. Patients received 500 mg/100 ml nab-paclitaxel administered in 6 weekly intravesical instillations. Efficacy was evaluated with cystoscopy, biopsy, cytology and imaging. If complete response was achieved, patients were treated with full dose monthly maintenance treatments for 6 months. RESULTS: A total of 28 patients were enrolled in the study. Of these patients 10 (35.7%) exhibited a complete response after initial treatment. At 1 year all of these responses remained durable after maintenance therapy. At a mean followup of 21 months (range 5 to 47) 19 of 28 (67.8%) patients retained their bladders without progression or distant metastases. A single patient had progression to muscle invasive disease at radical cystectomy. Treatment related adverse events were noted in 9 of 28 (32.1%) patients and were limited to grade 1 or 2. CONCLUSIONS: Intravesical nab-paclitaxel has minimal toxicity and a 35.7% response rate in patients with nonmuscle invasive bladder cancer and previous bacillus Calmette-Guérin failure. Complete response remained durable at 1 year followup in this heavily pretreated patient population.

New agents for bacillus Calmette-Guérin-refractory nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: Radical cystectomy is the standard of care for patients who fail intravesical bacillus Calmette-Guérin (BCG) for nonmuscle invasive bladder cancer (NMIBC). For patients unwilling or unable to undergo cystectomy, numerous local therapies exist, although few are approved by the Food and Drug Administration. This review describes available therapies for this challenging clinical entity. RECENT FINDINGS: Combination intravesical chemotherapy, targeted therapy, and drug delivery enhancement have all been under recent investigation and are promising, although none has proven superior as of yet. SUMMARY: While BCG is standard treatment for intermediate and high-risk NMIBC, many patients fail therapy with recurrence or progression. Early cystectomy is the standard of care for BCG failure; however, many patients are unwilling or unable to undergo cystectomy. Multiple intravesical therapies have been used in this BCG failure population with moderate success, and, recently, technologies to improve drug delivery or create novel drugs have also been applied. Comparing efficacy of these therapies remain challenging as study cohorts are heterogeneous and study designs are variable. However, there are an increasing number of novel treatment options that can be offered to patients faced with recurrent NMIBC after BCG who seek bladder-sparing therapy.