Intake and digestion of non-traditional feedstuffs by farmed collared peccary (Mammalia, Tayassuidae)

To assess the ability of the collared peccary (Pecari tajacu) to digest dietary fiber, four adult male collared peccaries were randomly assigned to a 4 × 4 Latin square design to determine the effects of feeding non-traditional feed ingredients, taken from palm trees with different levels of dietary fiber, on intake and coefficient of total tract apparent digestibility (CTTAD) and mean retention time. Four experimental diets were provided ad libitum: corn and soybean meal-based control diet; corn and palm kernel cake-based diet; corn and peach palm byproduct-based diet; and hay, palm kernel cake, and peach palm byproductbased diet. The CTTAD of neutral detergent fiber and acid detergent fiber (ADF) were 0.80±0.09 and 0.61±0.21, respectively. Increasing levels of ADF in diets also linearly decreased the CTTAD of crude protein and gross energy, while increasing non-fiber carbohydrate linearly decreased the CTTAD of ADF. These results confirm the ability of peccaries to digest fiber. However, the intake of a high-moisture and lignified ingredient, as the peach palm byproduct, decreased feed intake of peccaries due to their relatively small forestomach volume, which in turn may decrease their performance when used for prolonged periods. Despite of that, collared peccary gain a significant benefit in digestibility of dietary fiber due to its complex stomach in which fermentation occurs. © 2018 Sociedade Brasileira de Zootecnia

The RNA-dependent DNA methylation pathway is required to restrict SPOROCYTELESS/NOZZLE expression to specify a single female germ cell precursor in Arabidopsis

In higher plants, the female germline is formed from the megaspore mother cell (MMC), a single cell in the premeiotic ovule. Previously, it was reported that mutants in the RNA-dependent DNA methylation (RdDM) pathway might be involved in restricting the female germline to a single nucellus cell. We show that the DRM methyltransferase double mutant drm1drm2 also presents ectopic enlarged cells, consistent with supernumerary MMC-like cells. In wild-type ovules, MMC differentiation requires SPOROCYTELESS/NOZZLE (SPL/NZZ), as demonstrated by the spl/nzz mutant failing to develop an MMC. We address the poorly understood upstream regulation of SPL/NZZ in ovules, showing that the RdDM pathway is important to restrict SPL/NZZ expression. In ago9, rdr6 and drm1drm2 mutants, SPL/NZZ is expressed ectopically, suggesting that the multiple MMC-like cells observed might be attributable to the ectopic expression of SPL/NZZ. We show that the ovule identity gene, SEEDSTICK, directly regulates AGO9 and RDR6 expression in the ovule and therefore indirectly regulates SPL/NZZ expression. A model is presented describing the network required to restrict SPL/NZZ expression to specify a single MMC.Marta A. Mendes, Rosanna Petrella, Mara Cucinotta, Edoardo Vignati, Stefano Gatti, Sara C. Pinto, Dayton C. Bird, Veronica Gregis, Hugh Dickinson, Matthew R. Tucker and Lucia Colomb

APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell-Mediated Antitumor Immune Responses

The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in theHER2 subtype of breast cancer and are associated with immunotherapy response in diverse cancer types. However, the direct consequences of APOBEC mutagenesis on the tumor immune microenvironment have not been thoroughly investigated. To address this, we developed syngeneic murine mammary tumor models with inducible expression of APOBEC3B. We found that APOBEC activity induced antitumor adaptive immune responses and CD4 T cell-mediated, antigen-specific tumor growth inhibition. Although polyclonal APOBEC tumors had a moderate growth defect, clonal APOBEC tumors were almost completely rejected, suggesting that APOBEC-mediated genetic heterogeneity limits antitumor adaptive immune responses. Consistent with the observed immune infiltration in APOBEC tumors, APOBEC activity sensitized HER2-driven breast tumors to anti- CTLA-4 checkpoint inhibition and led to a complete response to combination anti-CTLA-4 and anti-HER2 therapy. In human breast cancers, the relationship between APOBEC mutagenesis and immunogenicity varied by breast cancer subtype and the frequency of subclonal mutations. This work provides a mechanistic basis for the sensitivity of APOBEC tumors to checkpoint inhibitors and suggests a rationale for using APOBEC mutational signatures and clonality as biomarkers predicting immunotherapy response in HER2-positive (HER2 ) breast cancers

A novel enzymatically-mediated drug delivery carrier for bone tissue engineering applications: combining biodegradable starch-based microparticles and differentiation agents

In many biomedical applications, the performance of biomaterials depends largely on their degradation behavior. For instance, in drug delivery applications, the polymeric carrier should degrade under physiological conditions slowly releasing the encapsulated drug. The aim of this work was, therefore, to develop an enzymaticmediated degradation carrier system for the delivery of differentiation agents to be used in bone tissue engineering applications. For that, a polymeric blend of starch with polycaprolactone (SPCL) was used to produce a microparticle carrier for the controlled release of dexamethasone (DEX). In order to investigate the effect of enzymes on the degradation behavior of the developed system and release profile of the encapsulated osteogenic agent (DEX), the microparticles were incubated in phosphate buffer solution in the presence of a-amylase and/or lipase enzymes (at physiological concentrations), at 37 C for different periods of time. The degradation was followed by gravimetric measurements, scanning electron microscopy (SEM) and Fourier transformed infrared (FTIR) spectroscopy and the release of DEX was monitored by high performance liquid chromatography (HPLC). The developed microparticles were shown to be susceptible to enzymatic degradation, as observed by an increase in weight loss and porosity with degradation time when compared with control samples (incubation in buffer only). For longer degradation times, the diameter of the microparticles decreased significantly and a highly porous matrix was obtained. The in vitro release studies showed a sustained release pattern with 48% of the encapsulated drug being released for a period of 30 days. As the degradation proceeds, it is expected that the remaining encapsulated drug will be completely released as a consequence of an increasingly permeable matrix and faster diffusion of the drug. Cytocompatibility results indicated the possibility of the developed microparticles to be used as biomaterial due to their reduced cytotoxic effects

Medication reconciliation as a strategy for preventing medication errors

ABSTRACT One of the current barriers proposed to avoid possible medication errors, and consequently harm to patients, is the medication reconciliation, a process in which drugs used by patients prior to hospitalization can be compared with those prescribed in the hospital. This study describes the results of a pharmacist based reconciliation conducted during six months in clinical units of a university hospital. Fourteen patients (23.33%) had some kind of problem related to medicine. The majority (80%) of medication errors were due to medication omission. Pharmaceutical interventions acceptance level was 90%. The results suggest that pharmacists based reconciliation can have a relevant role in preventing medication errors and adverse events. Moreover, the detailed interview, conducted by the pharmacist, is able to rescue important information regarding the use of drugs, allowing to avoid medications errors and patient injury

Preparation and scale up of extended-release tablets of bromopride

Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm) software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm) software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed