Investigating driver injury severity patterns in rollover crashes using support vector machine models

Rollover crash is one of the major types of traffic crashes that induce fatal injuries. It is important to investigate the factors that affect rollover crashes and their influence on driver injury severity outcomes. This study employs support vector machine (SVM) models to investigate driver injury severity patterns in rollover crashes based on two-year crash data gathered in New Mexico. The impacts of various explanatory variables are examined in terms of crash and environmental information, vehicle features, and driver demographics and behavior characteristics. A classification and regression tree (CART) model is utilized to identify significant variables and SVM models with polynomial and Gaussian radius basis function (RBF) kernels are used for model performance evaluation. It is shown that the SVM models produce reasonable prediction performance and the polynomial kernel outperforms the Gaussian RBF kernel. Variable impact analysis reveals that factors including comfortable driving environment conditions, driver alcohol or drug involvement, seatbelt use, number of travel lanes, driver demographic features, maximum vehicle damages in crashes, crash time, and crash location are significantly associated with driver incapacitating injuries and fatalities. These findings provide insights for better understanding rollover crash causes and the impacts of various explanatory factors on driver injury severity patterns.     

Impact of Serum Chemerin Levels on Liver Functional Reserves and Platelet Counts in Patients with Hepatocellular Carcinoma

Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma (HCC) patients and on the recurrence and prognosis of HCC. This study included 44 patients with any stage of HCC who underwent curative treatment at Gifu Municipal Hospital (Gifu, Japan) between 2006 and 2007. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Serum albumin levels (Pearson’s correlation coefficient; r = 0.3110, p = 0.0399), platelet counts (r = 0.4159, p = 0.0050), and prothrombin times (r = 0.3775, p = 0.0115) were significantly correlated with serum chemerin levels in patients with HCC, and they were inversely correlated with Child-Pugh scores (r = −0.3732, p = 0.0126), serum alanine aminotransferase levels (r = −0.3864, p = 0.0105), and total bilirubin levels (r = −0.4023, p = 0.0068). Among these variables, a multiple comparison test identified that platelet counts and total bilirubin levels were associated with serum chemerin levels (p < 0.0083). No significant correlation was found between serum chemerin levels and recurrence-free survival (p = 0.3691) or overall survival (p = 0.7916). In HCC patients, serum chemerin concentrations were correlated with liver functional reserves and platelet counts, but not with recurrence or prognosis.     

Thermal properties of duck fatty liver (foie gras) products

Thermal properties of duck fatty liver (foie gras), foie gras emulsion and fatty liver fat, as well as regular duck fat, were determined as a function of temperature. Density of foie gras and foie gras fat and emulsion at 20°C was measured as 947, 836, and 928 kg/m³, respectively. Differential scanning calorimetry thermograms for foie gras fat resulted in melting points ranging from –20 to 40°C. Values for the specific heat at 65°C for the fatty liver, its emulsion and fat, and duck fat were 1.79, 2.38, 1.71, and 2.48 J/g°C, respectively. Thermal conductivity of foie gras (organ) and its emulsion at 40°C was determined as 0.330 and 0.428 W/m°C, respectively. Mathematical models based on composition and temperature were developed for all the thermal properties obtained in this work.     

Prepartum dietary energy intake alters hepatic expression of genes related to peroxisome proliferator-activated receptor and inflammation in peripartal dairy cows

We determined the effect of prepartum plane of energy intake on liver function and metabolism pre- and postpartum by combining in vivo and in vitro data with mRNA expression data. A subset of multiparous prepartal Holsteins (n = 18) from a previously conducted experiment consumed 1 of 3 amounts of dietary energy intake, relative to their requirements. A diet formulated to allow consumption of ≥150% of net energy requirements during the far-off dry period and the close-up dry period was fed for ad libitum intake (150E) or in restricted amounts so that cows consumed 80% of requirements for energy (80E). A second diet was formulated to include wheat straw (26.1% of dry matter) to limit energy intake to 100% of NRC (2001) requirements for energy when fed ad libitum during the far-off period (100E). In the close-up period, 100E was fed the 150E diet for ad libitum intake. Expression of mRNA for genes related to fatty acid oxidation (PPARA, CPT1A, ACOX1) was greater for 100E cows than 150E cows on d 14 postpartum. These expression patterns were related to in vitro data for conversion of palmitate to CO₂, acid-soluble products, and esterified products by liver slices. Abundance of mRNA for PC displayed a sharp peak for all groups on d 1 postpartum, but serum glucose did not reflect this peak. The mRNA expression of SREBF1 was greater for 150E and 100E cows prepartum compared with 80E, and was positively related to rate of palmitate esterification postpartum. Expression of NR1H3 (LXRA) mRNA was greater for 100E cows on d 14 postpartum compared with 150E cows, which corresponded to expression of PPARA. An inflammatory response occurred in the liver around the time of parturition for 150E cows, as expression of IL1B was elevated both pre- and postpartum compared with 100E cows. The spike in IL1B expression for 150E cows on d 14 postpartum corresponded to the peak concentration of total lipids in liver tissue for all groups in this experiment. Overconsumption of energy prepartum was detrimental to the expression of important genes related to PPAR and liver function, especially postpartum. Furthermore, results provide evidence for inflammation related to accumulation of lipids in liver and overnutrition prepartum.     

一例血凝酶制剂致低纤维蛋白原血症患者的药学监护

目的: 探讨蛇毒血凝酶制剂在肝硬化患者应用中的药学监护。方法: 临床药师参与一例肝硬化伴低纤维蛋白原血症患者的治疗，根据国家药品不良反应监测中心的评价标准进行药学评价，判断为蛇毒血凝酶制剂所致不良反应，建议避免使用相关药物并对该患者进行药学监护。结果: 临床药师利用专业知识提供合理化用药建议，被临床医生接纳，及时有效地处理药物不良反应，使患者得到有效治疗后顺利出院。结论: 临床药师参与肝硬化患者的治疗过程，开展药学服务，可提供合理、有效的用药建议以确保患者用药安全。     

Corticosteroids in liver and urine in Sicilian cattle by a LC-MS/MS method

The presence of corticosteroid residues was assessed in urine and liver samples from livestock of Sicily. A total of 630 bovine samples were collected from farms and slaughterhouses. The samples were analysed using solid-phase extraction (SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS). All the corticosteroids found were under the maximum residue limit imposed by Commission Regulation (EC) 37/2010. About 4% of liver samples showed dexamethasone levels above the limit of detection (LOD), with a mean of 1.5 ± 0.2 µg kg^?1. Betamethasone was found only in seven liver samples, with a mean of 1.6 ± 0.1 µg kg^?1. Furthermore, prednisolone and prednisone were found only in urine and liver samples from slaughterhouse, probably related to the high rate of stress for bovines. These results suggest good control practices adopted by Sicilian farms, able to ensure the quality of food products.     

Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. II. Pharmacokinetics,whole-animal performance,and lipid metabolism

Dairy cows cope with severe energy insufficiency in early lactation by engaging in intense and sustained mobilization of fatty acids from adipose tissue. An unwanted side effect of this adaptation is excessive lipid accumulation in the liver, which in turn impairs hepatic functions. Mice experiencing increased hepatic fatty acid flux are protected from this condition through coordinated actions of the newly described hormone fibroblast growth factor-21 (FGF21) on liver and adipose tissue. The possibility of an analogous role for FGF21 in dairy cows is suggested by its rapid increase in plasma levels around parturition followed by chronically elevated levels in the first few weeks of lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either an excipient (control; n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight (BW) followed 2 d later by a constant i.v. infusion of FGF21 at a rate of 6.3 mg/kg of metabolic BW for 9 consecutive days. After bolus administration, human FGF21 circulated with a half-life of 194 min, and its constant infusion increased total plasma concentration 117-fold over levels in excipient-infused cows. The FGF21 treatment had no effect on voluntary feed intake, milk yield, milk energy output, or net energy balance measured over the 9-d infusion or on final BW. Plasma fatty acids circulated at lower concentrations in the FGF21 group than in the control group for the 8-h period following bolus administration, but this reduction was not significant during the period of constant i.v. infusion. Treatment with FGF21 caused a 50% reduction in triglyceride content in liver biopsies taken at the end of the constant i.v. infusion without altering the mRNA abundance of key genes involved in the transport, acyl coenzyme A activation, or oxidation of fatty acids. In contrast, FGF21 treatment ablated the recovery of plasma insulin-like growth factor-1 seen in control cows during the 9-d i.v. infusion period despite a tendency for higher plasma growth hormone. This effect was associated with increased hepatic mRNA abundance of the intracellular inhibitor of growth hormone receptor trafficking, LEPROT. Overall, these data confirm the ability of FGF21 to reduce lipid accumulation in bovine liver and suggest the possibility that FGF21 does so by attenuating the hepatic influx of adipose tissue-derived fatty acids.     

The Tumor Microenvironment in Liver Metastases from Colorectal Carcinoma in the Context of the Histologic Growth Patterns

Colorectal carcinoma (CRC) is the third most common cancer. Likewise, it is a disease that has a long survival if it is prematurely detected. However, more than 50% of patients will develop metastases, mainly in the liver (LM-CRC), throughout the evolution of their disease, which accounts for most CRC-related deaths. Treatment it is certainly a controversial issue, since it has not been shown to increase overall survival in the adjuvant setting, although it does improve disease free survival (DFS). Moreover, current chemotherapy combinations are administered based on data extrapolated from primary tumors (PT), not considering that LM-CRC present a very particular tumor microenvironment that can radically condition the effectiveness of treatments designed for a PT. The liver has a particular histology and microenvironment that can determine tumor growth and response to treatments: double blood supply, vascularization through fenestrated sinusoids and the presence of different mesenchymal cell types, among other particularities. Likewise, the liver presents a peculiar immune response against tumor cells, a fact that correlates with the poor response to immunotherapy. All these aspects will be addressed in this review, putting them in the context of the histological growth patterns of LM-CRC, a particular pathologic feature with both prognostic and predictive repercussions.     

Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.