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The objective of these studies was to determine the effects of feeding a novel rumen-protected Lys (RP-Lys) product on plasma AA, lactational performance, and Lys bioavailability. To evaluate RP-Lys on lactation performance a corn-based diet (42.5% of corn silage and 21.9% of corn and corn by-products, on DM basis) was formulated to be Lys deficient but adequate in Met, energy, and metabolizable protein. Thirty-six lactating Holstein cows were fed either a Lys-deficient control diet (CON) with no added RP-Lys, or diets containing 0.3% of RP-Lys (0.3RP-Lys) or 0.6% of RP-Lys (0.6RP-Lys) for 8 wk. There were no effects on dry matter intake (mean ± SD; 26.1 ± 0.58 kg/d), milk yield (37.9 ± 0.72 kg/d), or milk composition to the RP-Lys supplementation. No effect was observed on plasma AA concentrations except for His. Plasma His was linearly reduced by Lys feeding (42.6, 41.2, 30.0 ± 4.09 µM, for CON, 0.3RP-Lys, and 0.6RP-Lys, respectively). Calculated efficiency of Lys utilization decreased linearly with RP-Lys supplementation. In the companion study, 3 rumen-cannulated lactating dairy cows were used in a 3 × 3 Latin square design to assess the bioavailability of the RP-Lys. Free Lys (HCl-Lys), RP-Lys, and water were administered separately by postruminal bolus dosing. The Lys bioavailability was assessed by the ratio of area under the curve of Lys plasma concentration for RP-Lys compared with HCl-Lys and discounted for the area under the curve for water bolus dose. The estimated bioavailability of the RP-Lys was 24.4% ± 4.61. In summary, increased supplemental doses of Lys had no effect on Lys plasma concentration and lactational performance when fed to dairy cows on a corn-based diet, although altered Lys as % of essential AA was observed. However, the lack of effects should be considered in light of the lower-than-expected bioavailability of the RP-Lys.

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O objetivo deste estudo foi avaliar os efeitos das estações do parto e da inseminação, da retenção de placenta, da natimortalidade e da ordem de parto sobre o desempenho reprodutivo de vacas leiteiras. Utilizou-se a regressão logística, em que as variáveis dependentes foram concepção à primeira inseminação pós-parto e percentual de vacas prenhes no rebanho aos 100, 150 ou 200 DEL e as variáveis independentes foram a estação do parto e a estação da inseminação, a retenção de placenta, a natimortalidade e a ordem de parto. A estação do parto e a estação da inseminação influenciaram o desempenho reprodutivo, reduzindo a fertilidade das vacas nas estações quentes do ano. O atraso na primeira inseminação aumentou a concepção na primeira inseminação, mas reduziu o percentual de vacas prenhes ao longo da lactação. O desempenho reprodutivo da vaca leiteira foi afetado por vários fatores, relacionados à vaca, ao ambiente e ao manejo a ela imposto.(AU)

The objective of this study was to evaluate the effects of the calving season, insemination, placenta retention, stillbirth and birth order on the reproductive performance of dairy cows. Logistic regression was used, where the dependent variables were conception at the first postpartum insemination and the percentage of cows pregnant in the herd at 100, 150 and 200 DEL. The independent variables were delivery season and insemination season, placenta retention, stillbirth and delivery order. The calving season and the insemination season influenced reproductive performance, and in the hot seasons of the year the fertility of the cows was reduced. The delay in the first insemination increased conception in the first insemination but reduced the percentage of pregnant cows during lactation. The reproductive performance of the dairy cow was affected by several factors, related to the cow, the environment and the management imposed on it.(AU)

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Solanum lycocarpum fruits contain two major glycoalkaloids (GAs), solamargine (SM) and solasonine (SS). These compounds are reported as cytotoxic. However, they have poor water solubility and low bioavailability. To overcome these disadvantages and getting an efficient formulation the current study aimed to develop, characterize, and test the effectiveness of a nanotechnology-based strategy using poly(D,L-lactide) (PLA) nanoparticles functionalized with folate as delivery system of glycoalkaloidic extract (AE) for bladder cancer therapy. The strategic of adding folic acid into nanoformulations can increase the selectivity of the compounds to the cancer cells reducing the side effects. Our results revealed the successful preparation of AE-loaded folate-targeted nanoparticles (NP-F-AE) with particle size around 177 nm, negative zeta potential, polydispersity index <0.20, and higher efficiency of encapsulation for both GAs present in the extract (>85 %). To investigate the cellular uptake, the fluorescent dye coumarin-6 was encapsulated into the nanoparticle (NP-F-C6). The cell studies showed high uptake of nanoparticles by breast (MDA-MB-231) and bladder (RT4) cancer cells, but not for normal keratinocytes cells (HaCaT) indicating the target uptake to cancer cells. The cytotoxicity of nanoparticles was evaluated on RT4 2D culture model showing 2.16-fold lower IC50 than the free AE. Furthermore, the IC50 increased on the RT4 spheroids compared to 2D model. The nanoparticles penetrated homogeneously into the urotheliumof porcine bladder. These results showed that folate-conjugated polymeric nanoparticles are potential carriers for targeted glycoalkaloidic extract delivery to bladder cancer cells.

RESUMO

The objective for this study was to evaluate the supplementation with different non-fibrous carbohydrate (NFC) sources for grazing dairy cows in diets with high or low concentrations of rumen undegradable protein (RUP). Twelve multiparous cows averaging 30kg/d of milk production and 45±23 days in milk in a 4x4 Latin square design with 2 × 2 factorial arrangement were used. The difference in NFC content of the diets was achieved using ground corn (GC) or dried citrus pulp (DCP). Dietary RUP was altered by the partial replacement of soybean meal (LRUP) by roasted whole soybean and corn gluten meal (HRUP). Greater dry matter intake (DMI) was observed in DCP treatments compared to GC treatments (19.2 and 17.7kg/day of DM, respectively). Milk fat concentration was lower for LRUP treatments (3.4%) when compared to HRUP (3.6%). The milk protein concentration was greater for GC treatments (2.9%) in relation to DCP treatments (2.8%). Lower milk ureic nitrogen was observed when DCP diets were fed compared to those with GC (17.8 and 21.2mg/dL, respectively). The use of DCP as CNF source increased dry matter intake as well as milk fat concentration, although no differences in milk production were observed for RUP level.(AU)

Objetivou-se avaliar a suplementação com diferentes fontes de carboidratos não fibrosos (CNF) em vacas manejadas a pasto em dietas com alta ou baixa concentração de proteína não degradável no rúmen (PNDR). Doze vacas multíparas com média de 30kg leite/ dia e 45±23 dias em lactação foram utilizadas em delineamento quadrado latino 4x4 com arranjo fatorial 2 × 2. As fontes de CNF foram milho moído (MM) e polpa cítrica seca (PC). A PNDR da dieta foi alterada pela substituição parcial do farelo de soja da dieta de baixa PNDR (BPNDR) por grão de soja tostado e farelo de glúten de milho dieta de alta PNDR (APNDR). Foi observado maior consumo de matéria seca (CMS) nos tratamentos com PC quando comparado aos tratamentos com MM (19,2 e 17,7kg / dia de MS, respectivamente). O teor de gordura do leite foi menor para os tratamentos com BPNDR (3,4%) em comparação aos tratamentos com APNDR (3,6%). O teor de proteína do leite foi maior nos tratamentos com MM (2,9%) em relação aos tratamentos com PC (2,8%). Foram observados menores teores de nitrogênio ureico no leite dos animais alimentados com PC em relação aos com MM (17,8 e 21,2mg / dL, respectivamente). O uso de PC como fonte de CNF aumentou o consumo de matéria seca, bem como o teor de gordura do leite, embora não tenham sido observadas diferenças na produção de leite relacionada a alteração nos teores de PNDR.(AU)

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The objective for this study was to evaluate the supplementation with different non-fibrous carbohydrate (NFC) sources for grazing dairy cows in diets with high or low concentrations of rumen undegradable protein (RUP). Twelve multiparous cows averaging 30kg/d of milk production and 45±23 days in milk in a 4x4 Latin square design with 2 × 2 factorial arrangement were used. The difference in NFC content of the diets was achieved using ground corn (GC) or dried citrus pulp (DCP). Dietary RUP was altered by the partial replacement of soybean meal (LRUP) by roasted whole soybean and corn gluten meal (HRUP). Greater dry matter intake (DMI) was observed in DCP treatments compared to GC treatments (19.2 and 17.7kg/day of DM, respectively). Milk fat concentration was lower for LRUP treatments (3.4%) when compared to HRUP (3.6%). The milk protein concentration was greater for GC treatments (2.9%) in relation to DCP treatments (2.8%). Lower milk ureic nitrogen was observed when DCP diets were fed compared to those with GC (17.8 and 21.2mg/dL, respectively). The use of DCP as CNF source increased dry matter intake as well as milk fat concentration, although no differences in milk production were observed for RUP level.(AU)

Objetivou-se avaliar a suplementação com diferentes fontes de carboidratos não fibrosos (CNF) em vacas manejadas a pasto em dietas com alta ou baixa concentração de proteína não degradável no rúmen (PNDR). Doze vacas multíparas com média de 30kg leite/ dia e 45±23 dias em lactação foram utilizadas em delineamento quadrado latino 4x4 com arranjo fatorial 2 × 2. As fontes de CNF foram milho moído (MM) e polpa cítrica seca (PC). A PNDR da dieta foi alterada pela substituição parcial do farelo de soja da dieta de baixa PNDR (BPNDR) por grão de soja tostado e farelo de glúten de milho dieta de alta PNDR (APNDR). Foi observado maior consumo de matéria seca (CMS) nos tratamentos com PC quando comparado aos tratamentos com MM (19,2 e 17,7kg / dia de MS, respectivamente). O teor de gordura do leite foi menor para os tratamentos com BPNDR (3,4%) em comparação aos tratamentos com APNDR (3,6%). O teor de proteína do leite foi maior nos tratamentos com MM (2,9%) em relação aos tratamentos com PC (2,8%). Foram observados menores teores de nitrogênio ureico no leite dos animais alimentados com PC em relação aos com MM (17,8 e 21,2mg / dL, respectivamente). O uso de PC como fonte de CNF aumentou o consumo de matéria seca, bem como o teor de gordura do leite, embora não tenham sido observadas diferenças na produção de leite relacionada a alteração nos teores de PNDR.(AU)

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PURPOSE: To investigate the association of hypoenhancement on dynamic Contrast enhanced (DCE) with prostate cancer patient outcomes. MATERIAL AND METHODS: This was a single-institution retrospective Institutional Review Board (IRB)-approved cohort study of 54 men who had prostate Magnetic Resonance Imaging (MRI) within 6 months of cancer diagnosis between 01/2012 to 03/2014. Two readers independently identified the dominant MRI-lesions utilizing Prostate Imaging-Reporting and Data System-version2- guidelines. These lesions were classified as hypoenhancing or hyperenhancing, compared to normal peripheral zone using quantitative DCE analysis. The t test for unequal sample sizes and the two-sample Wilcoxon rank-sum tests were used to compare groups. Logistic regression determined if DCE characteristics predict the development of metastases or prostate cancer death. RESULTS: Time-to-progression was significantly shorter for hypoenhancing tumors (6.2 vs. 24.8 months, p = 0.05). Men with these lesions had a higher odds of having poor outcome (univariate logistic regression, odds ratio (OR) 6.79, 95% confidence interval (CI) 1.45-31.72, p = 0.02; multivariate analysis, OR 2.05, 95% CI 0.30-13.72, p = 0.47). Hypoenhancing tumors were larger (33.1 vs. 19.1 mm, p < 0.001) and more likely to be intermediate (Gleason scores 3 + 4 and 4 + 3) and high-grade (Gleason scores ≥ 4 + 4) prostate cancers (p = 0.05). Men in the hypoenhancing group had a higher mean prostate-specific antigen (PSA) value (87.6 vs. 24.8 ng/dL, p = 0.01) and PSA density (1.54 vs. 0.72, p = 0.03). The mean Ktrans and kep of hypoenhancing lesion were lower when compared to hyperenhancing lesions (p = 0.03 and p = 0.04). Ve values did not differ (p = 0.25). CONCLUSION: Men with hypoenhancing prostate cancers may have a worse prognosis than men with hyperenhancing tumors.

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Background: PTEN loss is observed in 20­30% of prostate cancers and is associated with a poor outcome, but clinical details of the impact of this biomarker are unclear for intermediate grade tumors. Methods: We investigated 43 radical prostatectomy-derived grade 7 prostate tumors from the Clinics Hospital of Ribeirão Preto. Tissue microarray (TMA) blocks were constructed and PTEN copy number status was determined for all patients through fluorescence in situ hybridization (FISH). To determine the presence of PTEN protein loss in our study cohort, we performed immunohistochemistry (IHC) in TMA sections. We then developed an automated algorithm in HALO™ to identify regions of PTEN protein loss in whole prostate scanned sections from ten patients with known PTEN deletion status by FISH. Clinical analyses were conducted to determine the associations between PTEN loss and patient outcome. All statistical analyses were conducted in R v3.4.3 with P-values below 0.05 being considered statistically significant. Results: In this study of 43 grade 7 tumors, we found PTEN deletions by FISH in 18.9% of tumors, and PTEN protein loss by IHC in 16.3% of tumors. Both techniques were highly concordant and complementary. Clinical analysis demonstrated that PTEN deletion by FISH was significantly associated with positive margin invasion (P = 0.04) and Gleason score upgrade (P = 0.001). Digital image analysis of ten representative tumors demonstrated distinct intratumoral heterogeneity for PTEN protein loss in four tumors. Conclusions: This study shows that PTEN loss in Gleason grade 7 tumors can be heterogeneous and that a systematic analysis of this biomarker using a combination of FISH, IHC, and digital imaging may identify patients with a greater risk of poor outcome (AU)

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Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.

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Objetivou-se avaliar os desempenhos produtivo e reprodutivo de vacas F1 Holandês x Gir Minas Gerais, as quais foram mantidas em sistema de produção a pasto no verão, com suplementação de concentrado, e, no inverno, alimentadas com cana-de-açúcar, polpa de citros e concentrado. As características avaliadas foram: idade ao primeiro parto, intervalo parto-primeiro serviço, período de serviço, intervalo de partos, permanência da matriz no rebanho, produção de leite total por lactação, duração da lactação, produção média diária, produções ajustadas a 280 dias e a 305 dias de lactação, produção de leite por intervalo de partos e curvas de lactação conforme ordem de partos, época de partos e período de serviço. A função gama incompleta foi utilizada para estimação dos parâmetros das curvas de lactação. As demais características foram analisadas utilizando-se modelos lineares mistos. O rebanho apresentou ótimo desempenho (6271,56kg de leite por lactação). As fêmeas F1 Holandês x Gir são boa alternativa para a produção de leite, desde que garantidas boas condições de manejo, alimentação do rebanho e utilização de matrizes oriundas de programas de cruzamento direcionados empregando-se critérios de melhoramento genético.(AU)

The objective was to evaluate the productive and reproductive performances of F1 Holstein x Gir cows in the state of Minas Gerais. The herd during the summer was managed in a pasture based production system with supplementation of concentrate according to milk production and in the winter it was fed with sugar cane, citrus pulp and concentrate. The characteristics evaluated were: age at first calving, calving to first service interval, service period, calving interval, permanence the cows in the herd, total milk production per lactation, lactation length, average milk daily, productions adjusted to 280 and to 305 days of lactation, milk production per calving interval, and lactation curves. The Incomplete Gamma function was used to estimate the parameters of lactation curves at parturition order, parturition epoch and service period. The other characteristics were analyzed using linear mixed models. The herd showed great performance (6271,56 kg of milk per lactation). F1 Holstein x Gir cows are a good alternative to milk production, as long as good conditions of handling and feeding are guaranteed, and the use of cows derived from breeding programs targeted using genetic improvement criteria.(AU)

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Objetivou-se avaliar os desempenhos produtivo e reprodutivo de vacas F1 Holandês x Gir Minas Gerais, as quais foram mantidas em sistema de produção a pasto no verão, com suplementação de concentrado, e, no inverno, alimentadas com cana-de-açúcar, polpa de citros e concentrado. As características avaliadas foram: idade ao primeiro parto, intervalo parto-primeiro serviço, período de serviço, intervalo de partos, permanência da matriz no rebanho, produção de leite total por lactação, duração da lactação, produção média diária, produções ajustadas a 280 dias e a 305 dias de lactação, produção de leite por intervalo de partos e curvas de lactação conforme ordem de partos, época de partos e período de serviço. A função gama incompleta foi utilizada para estimação dos parâmetros das curvas de lactação. As demais características foram analisadas utilizando-se modelos lineares mistos. O rebanho apresentou ótimo desempenho (6271,56kg de leite por lactação). As fêmeas F1 Holandês x Gir são boa alternativa para a produção de leite, desde que garantidas boas condições de manejo, alimentação do rebanho e utilização de matrizes oriundas de programas de cruzamento direcionados empregando-se critérios de melhoramento genético.(AU)

The objective was to evaluate the productive and reproductive performances of F1 Holstein x Gir cows in the state of Minas Gerais. The herd during the summer was managed in a pasture based production system with supplementation of concentrate according to milk production and in the winter it was fed with sugar cane, citrus pulp and concentrate. The characteristics evaluated were: age at first calving, calving to first service interval, service period, calving interval, permanence the cows in the herd, total milk production per lactation, lactation length, average milk daily, productions adjusted to 280 and to 305 days of lactation, milk production per calving interval, and lactation curves. The Incomplete Gamma function was used to estimate the parameters of lactation curves at parturition order, parturition epoch and service period. The other characteristics were analyzed using linear mixed models. The herd showed great performance (6271,56 kg of milk per lactation). F1 Holstein x Gir cows are a good alternative to milk production, as long as good conditions of handling and feeding are guaranteed, and the use of cows derived from breeding programs targeted using genetic improvement criteria.(AU)

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