Graduate Student Literature Review: System, plant, and animal factors controlling dietary pasture inclusion and their impact on ration formulation for dairy cows.

Diet formulation in a pasture-based dairy system is a challenge as the quality and quantity of available pasture, which generally constitutes the base diet, is constantly changing. The objective of this paper is to cover a more in-depth review of the nutritional characteristics of pasture-based diets, identifying potential system, plant, and animal factors that condition pasture dietary inclusion in dairy cows. In practice, there is a wide diversity of pasture-based systems with predominant to minimal use of pasture requiring a more specific classification that potentially considers the amount and time of access to pasture, access to housing, length of grazing season, seasonality of calving, and level and method of supplementation. There are important differences in the nutritional quality between pasture species and even cultivars. However, under management practices that promote maintenance of pasture in a vegetative state as well as controlling the availability of pasture, it is possible to achieve high dry matter intakes (∼2.9%-3.4% of live weight) of pasture with moderate to high diet energy density, protein supply, and digestibility. The amount of pasture to include in the diet will depend on several factors, such as the type of production system, the cost of supplementary feeds, and the farmer's objectives, but inclusions of ∼40% to 50% of the diet seem to potentially reduce costs while apparently not limiting voluntary feed intake. Considering that there seems to be a continuum of intermediate management systems, a better understanding of the factors inherent to the feed ingredients used, as well as the use of nutrients by cows, and potential interactions between animal × system should be addressed in greater depth. This requires a meta-analysis approach, but given the diversity of the pasture-based system in practice, the existing information is highly fragmented. A clear definition of "subsystems" is necessary to direct the future research and development of mechanistic models.

Prevalence of metabolic associated fatty liver disease (MAFLD) in patients with gallstone disease. Study on a cohort of cases in South-Southeastern Mexico.

INTRODUCTION: Metabolic (dysfunction) associated fatty liver disease (MAFLD) and gallstone disease are entities that share similar risk factors. Numerous publications confirm their elevated frequency, but few studies have considered their prevalence and possible association. AIMS: To determine the prevalence of MAFLD in patients with gallstone disease and the usefulness of liver biopsy for diagnosing the liver disease. MATERIALS AND METHODS: A prospective study was conducted on patients that underwent laparoscopic cholecystectomy, in whom liver biopsy was performed. VARIABLES ANALYZED: Anthropometric characteristics, biochemical profile, conventional ultrasound, risk factors, and histopathologic study of the liver biopsy. STATISTICAL ANALYSIS: Descriptive statistics were carried out for the quantitative variables and the Student's t test and multivariate analysis through binary logistic regression were employed for the continuous variables, utilizing IBM-SPSS, 25.0 (Windows) software. RESULTS: A total of 136 patients were classified into 2 groups: 40 (29.41%) with normal liver and 96 (70.59%) with MAFLD. Of the 136 patients, 71 patients (52.21%) corresponded to hepatic steatosis, 21 (15.44%) to steatohepatitis, and 4 (2.94%) to cirrhosis. Perisinusoidal inflammation was found in 39 cases (28.68%) and fibrosis was found in 10 (7.35%). The risk factors for both groups were age, diabetes, high blood pressure, and obesity. Glucose, triglyceride, and aminotransferase levels were significantly higher in the MAFLD group and conventional ultrasound demonstrated moderate concordance for its detection. DISCUSSION AND CONCLUSIONS: The results confirmed the elevated frequency of MAFLD associated with gallstone disease, justifying liver biopsy during cholecystectomy for diagnosing MAFLD.

Evaluation of Molly model predictions of ruminal fermentation, nutrient digestion, and performance by dairy cows consuming ryegrass-based diets.

Several studies have been conducted to improve grazing management and supplementation in pasture-based systems. However, it is necessary to develop tools that integrate the available information linking the representation of biological processes with animal performance for use in decision making. The objective of this study was to evaluate the precision and accuracy of the Molly cow model predictions of ruminal fermentation, nutrient digestion, and animal performance by cows consuming pasture-based diets to identify model strengths and weaknesses, and to derive new digestive parameters when relevant. Model modifications for adipose tissue, protein synthesis in lean body mass and viscera representation were included. Data used for model evaluations were collected from 25 publications containing 115 treatment means sourced from studies conducted with lactating dairy cattle. The inclusion criteria were that diets contained ≥45% perennial ryegrass (Lolium perenne L.), and that dry matter intake, dietary ingredient composition, and nutrient digestion observations were reported. Animal performance and N excretion variables were also included if they were reported. Model performance was assessed before and after model reparameterization of selected digestive parameters, global sensitivity analysis was conducted after reparameterization, and a 5-fold cross evaluation was performed. Although rumen fermentation predictions were not significantly improved, rumen volatile fatty acids absorption rates were recalculated, which improved the concordance correlation coefficient (CCC) for rumen propionate and ammonia concentration predictions but decreased CCC for acetate predictions. Similar degradation rates of crude protein were observed for grass and total mixed ration diets, but rumen-undegradable protein predictions seemed to be affected by the solubility of the protein source as was the intestinal digestibility coefficient. Ruminal fiber degradation was greater after reparameterization, driven primarily by hemicellulose degradation. Predictions of ruminal and fecal outflow of neutral detergent fiber and acid detergent fiber, as well as total fecal output predictions, improved significantly after reparameterization. Blood urea N and urinary N excretion predictions resulted in similar accuracy using both sets of model parameters, whereas fecal N excretion predictions were significantly improved after reparameterization. Body weight and body condition score predictions were greatly improved after model modifications and reparameterization. Before reparameterization, yield predictions for daily milk, milk fat, milk protein, and milk lactose were greatly overestimated (mean bias of 61.0, 58.7, 73.7, and 64.6% of mean squared error, respectively). Although this problem was partially addressed by model modifications and reparameterization (mean bias of 3.2, 1.1, 1.7, and 0.4% of mean squared error, respectively), CCC values were still small. The ability of the model to predict grass digestion and animal performance in dairy cows consuming pasture-based diets was improved, demonstrating the applicability of this model to these productive systems. However, the failure to predict grass digestion based on standard model inputs without reparameterization indicates there are still fundamental challenges in characterizing feeds for this model.

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder.

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target.

Safety of laparoscopic subtotal cholecystectomy in acute cholecystitis. Experience in Southeast Mexico. / Seguridad de la colecistectomía subtotal laparoscópica en colecistitis aguda. Experiencia en el sureste de México.

INTRODUCTION: Subtotal cholecystectomy has been employed in cases of tecnically difficult cholecystectomy to prevent common bile duct injury. Given that there are few reports in Mexico on the theme, we consider it important to present the 18-year experience of a surgical group in the South-Southeast of Mexico. AIM: To determine the safety of laparoscopic subtotal cholecystectomy in patients with acute cholecystitis. MATERIALS AND METHODS: A retrospective, observational, and comparative study was conducted on patients with gallstones that underwent laparoscopic cholecystectomy. The variables analyzed were: anthropometric characteristics, comorbidities, conversion rate, surgery duration, hospital stay, and morbidity and mortality. STATISTICAL ANALYSIS: Descriptive statistics were applied through measures of central tendency and dispersion and standard deviation, utilizing the SPSS v22 program. RESULTS: A total of 1,101 medical records of patients with gallstones were reviewed. Of those patients, 223 presented with acute cholecystitis (20.25%) and they were divided into 2 groups: A) total cholecystectomy (82.95%) and B) subtotal cholecystectomy (17.05%). The anthropometric characteristics, risk factors, conversion rate, and hospital stay were similar in both groups. Only surgery duration was longer in the subtotal cholecystectomy group. Complications were more frequent, there was 1 death, and there was no bile duct injury in the subtotal cholecystectomy group. Those results were not statistically significant between the two groups. CONCLUSIONS: Subtotal cholecystectomy is a valuable resource in patients with acute cholecystitis. In our case series, it was a safe and reliable procedure for preventing bile duct injury. A larger number of cases are needed to corroborate those results.

Micro-CT scouting for transmission electron microscopy of human tissue specimens.

Transmission electron microscopy (TEM) provides sub-nanometre-scale details in volumetric samples. Samples such as pathology tissue specimens are often stained with a metal element to enhance contrast, which makes them opaque to optical microscopes. As a result, it can be a lengthy procedure to find the region of interest inside a sample through sectioning. We describe micro-CT scouting for TEM that allows noninvasive identification of regions of interest within a block sample to guide the sectioning step. In a tissue pathology study, a bench-top micro-CT scanner with 10 µm resolution was used to determine the location of patches of the mucous membrane in osmium-stained human nasal scraping samples. Once the regions of interest were located, the sample block was sectioned to expose that location, followed by ultra-thin sectioning and TEM to inspect the internal structure of the cilia of the membrane epithelial cells with nanometre resolution. This method substantially reduced the time and labour of the search process from typically 20 sections for light microscopy to three sections with no added sample preparation.

PLK1 expression and BI 2536 effects in childhood acute lymphoblastic leukemia.

BACKGROUND: Polo-like kinase 1 (PLK1) is a conserved kinase that mediates various mitotic events. Compelling data have repeatedly demonstrated its upregulation in different neoplasia, being frequently associated with poor prognosis. However, in childhood acute lymphoblastic leukemia (ALL), no studies have yet been conducted. PROCEDURE: PLK1 expression and association with biological features were evaluated in 65 consecutively diagnosed childhood ALL samples by quantitative real-time PCR. Moreover, the effects of a specific PLK1 inhibitor, BI 2536, was tested against a panel of nine ALL cell lines at nanomolar concentrations (10, 50, 100 nM). RESULTS: The mRNA expression of PLK1 showed great variability in pediatric ALL, but no difference was evidenced compared to normal bone marrow. Additionally, no association was found between PLK1 mRNA expression with any clinical or biological features. Alternatively, high mRNA expression of PLK1 was present in ALL cell lines. In vitro treatment with BI 2536 strongly diminished growth, while presenting significant reduction in colony formation capacity and increased apoptosis rates. Moreover, strong G2/M arrest was detected suggesting important impaired proliferation after treatment. CONCLUSIONS: PLK1 mRNA expression level is not associated with prognosis in childhood ALL; however, considering the great variability observed in the sample and the in vitro experiments presented herein, BI 2536 treatment might serve as a promising therapeutic to enhance the efficacy of conventional treatment modalities in some childhood ALL cases.

Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma.

Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient's median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines. Treatments with nanomolar concentrations of BI 2536, BI 6727, GW843682X or GSK461364 caused a significant decrease in GBM cells proliferation. Colony formation was also found to be inhibited (P<0.05), whereas apoptosis rate and mitotic index were significantly increased (P<0.05) after PLK1 inhibition in both GBM cell lines. Cell cycle analysis showed an arrest at G2 (P<0.05) and cell invasion was also decreased after PLK1 inhibition. Furthermore, simultaneous combinations of BI 2536 and temozolomide produced synergistic effects for both the cell lines after 48 h of treatment. Our findings suggest that PLK1 might be a promising target for the treatment of GBMs.

Inhibition of NF- κ B by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide and γ -Radiation Cytotoxicity in Glioblastoma Cells.

Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF- κ B is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF- κ B inhibitor with antiproliferative properties in GBM. In the present study, the ability of DHMEQ to surmount tumor's invasive nature and therapy resistance were further explored. Corroborating results showed that DHMEQ impaired cell growth in dose- and time-dependent manners with G2/M arrest when compared with control. Clonogenicity was also significantly diminished with increased apoptosis, though necrotic cell death was also observed at comparable levels. Notably, migration and invasion were inhibited accordingly with lowered expression of invasion-related genes. Moreover, concurrent combination with TMZ synergistically inhibited cell growth in all cell lines, as determined by proliferation and caspase-3 activation assays, though in those that express O(6)-methylguanine-DNA methyltransferase, the synergistic effects were schedule dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing radiation. Taken together, our results strengthen the potential usefulness of DHMEQ in future therapeutic strategies for tumors that do not respond to conventional approaches.

[Delay in hospitalization, diagnosis and surgical intervention in acute appendicitis]. / Retardo en la hospitalización, el diagnóstico y la intervención quirúrgica de la apendicitis aguda.

AIMS: To assess if self-medication delays diagnosis and Surgical Treatment in acute appendicitis and increases morbidity, mortality and hospital stay as well. DESIGN: Retrospective, comparative and observational study. STATISTICS: Chi square, exact Fisher test. SUBJECTS AND STUDY GROUPS: 57 patients were subjected to appendectomy and were stratified in three groups according to the lapse of time between initiation of symptoms and hospitalization: group A less than 24 h (n = 20), group B between 24 and 48 h (n = 17), and group C more than 48 h (n = 20). RESULTS: Groups B and C showed a significant delay for both diagnosis (p < 0.001) and surgical intervention (p < 0.001) in relation to group A. The incidence of acute abdomen presentation showed a positive trend with time of hospitalization (p = 0.03). Self-medication increased from group A to C (p < 0.001). Groups B and C showed a complication rate of 24 and 25%, respectively (p > 0.05). Conversely, group A had not complications (p < 0.05). In addition there was a 5% mortality due to sepsis in group C. Finally, hospital stay was longer in groups B and C (p < 0.001). CONCLUSIONS: Self-medication correlated with delayed hospitalization, diagnosis, treatment and complications. Hospital stay was consequently longer.

Angle closure glaucoma as initial manifestation of melanocytoma of the optic disc.

A 44-year-old man had progressive visual loss and pain due to angle-closure glaucoma associated with a papillary pigmented lesion. The eye was enucleated because of intractable pain and the suspicion of a malignant tumor. Histologic and electron microscopic examination of the enucleated eye revealed a partially necrotic melanocytoma of the optic nerve. There was histologic evidence of vaso-occlusive disease within the optic nerve that resulted in ischemic necrosis of the tumor, hypoxic retinopathy and neovascular glaucoma. This report emphasizes that significant complications may occur in otherwise typical intraocular nevi.