Driven by the large amount of goat milk destined for cheese production, and to pioneer the goat cheese industry, the objective of this study was to assess the effect of farm in predicting goat ...milk-coagulation and curd-firmness traits via Fourier-transform infrared spectroscopy. Spectra from 452 Sarda goats belonging to 14 farms in central and southeast Sardinia (Italy) were collected. A Bayesian linear regression model was used, estimating all spectral wavelengths' effects simultaneously. Three traditional milk-coagulation properties rennet coagulation time (min), time to curd firmness of 20 mm (min), and curd firmness 30 min after rennet addition (mm) and 3 curd-firmness measures modeled over time rennet coagulation time estimated according to curd firmness change over time (RCTeq), instant curd-firming rate constant, and asymptotical curd firmness were considered. A stratified cross validation (SCV) was assigned, evaluating each farm separately (validation set; VAL) and keeping the remaining farms to train (calibration set) the statistical model. Moreover, a SCV, where 20% of the goats randomly taken (10 replicates per farm) from the VAL farm entered the calibration set, was also considered (SCV80). To assess model performance, coefficient of determination (R2VAL) and the root mean squared error of validation were recorded. The R2VAL varied between 0.14 and 0.45 (instant curd-firming rate constant and RCTeq, respectively), albeit the standard deviation was approximating half of the mean for all the traits. Although average results of the 2 SCV procedures were similar, in SCV80, the maximum R2VAL increased at about 15% across traits, with the highest observed for time to curd firmness of 20 mm (20%) and the lowest for RCTeq (6%). Further investigation evidenced important variability among farms, with R2VAL for some of them being close to 0. Our work outlined the importance of considering the effect of farm when developing Fourier-transform infrared spectroscopy prediction equations for coagulation and curd-firmness traits in goats.
The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, ...we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median range plasma ISL levels of 1.3 1.0-2.5, 1.9 1.2-6.3 and 2.8 2.3-11.6, respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median range plasma ENG levels of 495 229-1110 pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.
Ancillary molecular testing has been advocated for diagnostic accuracy in the differentiation of lipomas from atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL); however, the ...implications and specific indications for use are not well-established in the current literature. Herein, we extend previous findings by quantitatively evaluating the impact of molecular testing of lipomatous neoplasms in our routine clinical practice, how it modifies the historical perspective of their clinical course, and the effect of distinct surgical procedures in modulating the risk of local recurrence for these tumors after molecular classification. On the basis of these analyses, we suggest a specific set of basic recommendations for complementary molecular assessment in the diagnosis of lipomatous tumors. Four hundred and five lipomatous neoplasms located in the trunk and extremities were analyzed histologically and for the presence of 12q13-15 amplification on paraffin-embedded tissues by assessing MDM2/CPM amplification. Survival analyses were calculated with Kaplan-Meier and compared with the log-rank. Multivariate analysis was evaluated by the Cox regression method. The 405 tumors were histologically classified as ordinary lipoma (n=324), intramuscular lipoma (n=29), and ALT/WDL (n=52). The level of agreement between the histologic diagnosis and the molecular diagnosis was high (96%) but pathologists showed a tendency to overestimate cytologic atypia and the diagnosis of ALT/WDL (precision, 79%; accuracy, 88%). Molecular assessment led to a major diagnostic reclassification in 18 tumors (4%). Eleven of the tumors histologically classified as ALT/WDL were reclassified as ordinary lipoma (n=5) and intramuscular lipoma (n=6); none of which recurred. Seven ordinary lipomas were reclassified as ALT/WDL, 6 of which were larger than 15 cm and deeply located; 2 recurred locally. After molecular data, the 5-year local recurrence rates for ordinary lipoma, intramuscular lipoma, and ALT/WDL were 1%, 12%, and 44%, respectively. Multivariate analyses after molecular assessment showed tumor type and type of resection to be associated with the risk of local recurrence. Complementary molecular testing refines the histologic classification of lipomatous tumors and better estimates the impact of surgical procedures on the risk of local recurrence. Pathologists tend to overestimate the degree of cytologic atypia and the indiscriminate use of molecular testing should be avoided, especially for extremity-based tumors. Molecular testing should be considered for "relapsing lipomas," tumors with questionable cytologic atypia (even if widely excised), or for large lipomatous tumors (>15 cm) without diagnostic cytologic atypia.
This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of all available treatments for severe melioidosis in decreasing hospital mortality and to identify eradication ...therapies with low disease recurrence rates and minimal risk of adverse drug events (AEs).
Relevant randomized controlled trials (RCT) were searched from Medline and Scopus databases from their inception until July 31, 2022. RCTs that compared the efficacy between treatment regimens for severe melioidosis or eradication therapy of melioidosis, measured outcomes of in-hospital mortality, disease recurrence, drug discontinuation, or AEs, were included for review. A two-stage NMA with the surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of treatment regimens.
Fourteen RCTs were included in the review. Ceftazidime plus granulocyte colony-stimulating factor (G-CSF), ceftazidime plus trimethoprim-sulfamethoxazole (TMP-SMX), and cefoperazone-sulbactam plus TMP-SMX had a lower mortality rate than other treatments and were ranked as the top three most appropriate treatments for severe melioidosis with the SUCRA of 79.7%, 66.6%, and 55.7%, respectively. However, these results were not statistically significant. For eradication therapy, treatment with doxycycline monotherapy for 20 weeks was associated with a significantly higher risk of disease recurrence than regimens containing TMP-SMX (i.e.,TMP-SMX for 20 weeks, TMP-SMX plus doxycycline plus chloramphenicol for more than 12 weeks, and TMP-SMX plus doxycycline for more than 12 weeks). According to the SUCRA, TMP-SMX for 20 weeks was ranked as the most efficacious eradication treatment (87.7%) with the lowest chance of drug discontinuation (86.4%), while TMP-SMX for 12 weeks had the lowest risk of AEs (95.6%).
Our results found a non-significant benefit of ceftazidime plus G-CSF and ceftazidime plus TMP-SMX over other treatments for severe melioidosis. TMP-SMX for 20 weeks was associated with a lower recurrence rate and minimal risk of adverse drug events compared to other eradication treatments. However, the validity of our NMA may be compromised by the limited number of included studies and discrepancies in certain study parameters. Thus, additional well-designed RCTs are needed to improve the therapy of melioidosis.
Introdução: as indústrias de processamento de frutas geram grande quantidade de biomassa residual que poderia ser reaproveitada. Considerando o elevado volume de resíduos produzidos pelo descarte das ...sementes do abacate e destacando o alto teor de compostos bioativos, é um produto interessante para ser avaliado. Objetivo: avaliar a composição centesimal da farinha das sementes de abacate e as propriedades antioxidantes e antimicrobianos dos seus extratos. Métodos: os extratos foram obtidos por maceração da farinha do caroço do abacate desidratada em diferentes temperaturas (4,25 e 60 °C) utilizando n-hexano e etanol como solventes. Resultados: verificou-se que a farinha é uma excelente fonte de carboidratos, com alto teor de fibras, proteínas e minerais (N, K, Mg e Ca, entre outros). A temperatura da extração influenciou tanto no rendimento como no conteúdo de fenóis totais, atividades antioxidantes e antimicrobianas dos extratos. Os extratos etanoicos obtidos à 60 °C apresentaram maior rendimento (18%) e teor de compostos fenólicos totais (~840 mgEAG/g). Também os extratos etanoicos apresentaram maior atividade antioxidante (IC50= 0,013 mg/mL e 0,018 mg/mL) em temperaturas mais baixas de extração, 4 °C e 25 °C, respectivamente. Já extrato hexanóico obtido à 4 °C apresentou maior atividade antimicrobiana para as quatro bactérias testadas (L. monocytogenes, S. aureus, S. choleraesuis e E. coli). Conclusão: a farinha obtida das sementes de abacate, apresentam alto valor biológico e podem ser usadas como suplementos na alimentação humana.
Trypanosoma evansi is an important pathogen that causes changes in nitric oxide (NO) levels and antioxidant enzymes, as well as oxidative stress. The present study evaluated the in vivo effect of ...T. evansi infection on frequency and index of DNA damage in liver, heart, spleen and total blood of rats. Twenty rats were assigned into two groups with ten rats each, being subdivided into four subgroups (A1 and A2, 5 animals/group; and B1 and B2, 5 animals/group). Rats in the subgroups A1 and A2 were used as control (uninfected) and animals in the subgroups B1 and B2 were inoculated with T. evansi (infected). NO in serum and the comet assay were used to measure DNA damage index (DI) and damage frequency (DF) in liver, heart, spleen and total blood of infected rats. Increased NO levels on days 3 and 9 post-infection (PI) was observed (P < 0.001). Also, it was verified an increase on DI and DF in the evaluated organs on days 3 and 9 PI (P < 0.001). Our data show that T. evansi infection causes genotoxicity due to the production of NO, causing not only the death of the protozoan, but also inducing DNA damage in the host.
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•Trypanosoma evansi infection cause increased frequency damage using comet assay.•T. evansi infection cause increased damage index using comet assay.•Histopathological alterations in liver, spleen and heart were observed.•T. evansi infection causes genotoxicity due to the production of NO.
Adipose tissue tumors of the retroperitoneum showing no identifiable cytologic atypia are usually classified as lipomalike well-differentiated liposarcoma. Whether a subset of these tumors represents ...true examples of retroperitoneal lipoma remains a controversial subject, because the diagnostic liposarcoma cells may be of difficult identification, even after extensive sampling. Herein, we describe a large retroperitoneal lipoma with classic histopathologic, cytogenetic, molecular cytogenetic, and molecular genetic features. Extensive morphologic inspection showed no evidence of cytologic atypia. Cytogenetic analysis performed on fresh tissue material revealed the classic lipoma chromosome t(3;12)(q27;q14-15). Fluorescence in situ hybridization on multiple sections excluded the presence of MDM2 and CDK4 amplification, but showed HMGA2 balanced rearrangement in most cells. Reverse-transcriptase polymerase chain reaction followed by sequencing analysis confirmed the presence of the HMGA2-LPP fusion gene, a characteristic and the most common fusion product found in lipoma. The patient has been followed for 2.5 years without evidence of recurrence or metastasis. These results indicate that retroperitoneal lipomata do exist, but their diagnosis must rely on stringent histologic, cytogenetic, and molecular genetic analysis.
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