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Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

Aim The financial burden of the increasing dialysis population challenges healthcare resources internationally. Home haemodialysis offers many benefits over conventional facility dialysis including superior clinical, patient-centred outcomes and reduced cost. This review updates a previous review, conducted a decade prior, incorporating contemporary home dialysis techniques of frequent and nocturnal dialysis. We sought comparative cost-effectiveness studies of home versus facility haemodialysis (HD) for people with end-stage kidney failure (ESKF). Methods We conducted a systematic review of literature from January 2000–March 2014. Studies were included if they provided comparative information on the costs, health outcomes and cost-effectiveness ratios of home HD and facility HD. We searched medical and health economic databases using MeSH headings and text words for economic evaluation and haemodialysis. Results Six studies of economic evaluations that compared home to facility HD were identified. Two studies compared home nocturnal HD, one home nocturnal and daily home HD, and three compared contemporary home HD to facility HD. Overall these studies suggest that contemporary home HD modalities are less costly and more effective than facility HD. Home HD start-up costs tend to be higher in the short term, but these are offset by cost savings over the longer term. Conclusions Contemporaneous dialysis modalities including nocturnal and daily home haemodialysis are cost-effective or cost-saving compared with facility-based haemodialysis. This result is largely driven by lower staff costs, and better health outcomes for survival and quality of life. Expanding the proportion of haemodialysis patients managed at home is likely to produce cost savings.

Professionals and professional firms provide a range of taxation-related services, from advising clients on their tax obligations to designing and implementing tax-reduction strategies. Provided that tax professionals respect the letter of the law, are all such tax services morally permissible? We answer this question in the negative by distinguishing between institutional integrity and institutional corruption in fiscal arrangements; tax services that promote a situation of fiscal institutional corruption are impermissible, given that they severely inhibit the ability of taxation institutions to collect revenue efficiently and equitably. The professional facilitation of abusive tax avoidance — explicit tax reduction that is contrary to the spirit or intent of the law — is a particularly prominent aspect of fiscal institutional corruption. We illustrate the role of professionals in designing, promoting and implementing abusive tax avoidance strategies through several case studies, including the Wyly offshore network and the KPMG tax shelter scandal. In addition, we claim that tax professionals have specific responsibilities to help remedy institutional corruption associated with abusive tax avoidance. To argue this thesis, we present general principles for assigning remedial responsibilities to particular agents. We then apply those principles to determine what three major groups of tax professionals — accountants, lawyers, and financial experts — ought to do about abusive tax avoidance.

Recent advances in technology facilitated development of large sets of genetic markers for many taxa, though most often model or domestic organisms. Cross-species application of genomic technologies may allow for rapid marker discovery in wild relatives of taxa with well-developed resources. We investigated returns from cross-species application of three commercially available SNP chips (the OvineSNP50, BovineSNP50 and EquineSNP50 BeadChips) as a function of divergence time between the domestic source species and wild target species. Across all three chips, we observed a consistent linear decrease in call rate (~1.5% per million years), while retention of polymorphisms showed an exponential decay. These results will allow researchers to predict the expected amplification rate and polymorphism of cross-species application for their taxa of interest, as well as provide a resource for estimating divergence times.

The morphology of the female reproductive system of Microctonus aethiopoides is described and illustrated, and an ultrastructural examination of the ovaries was carried out. Virus-like particles (VLPs) were initially found in the ovarial epithelial cells of females from pre-adult emergence from the pupal cocoon until at least 5 days after emergence. The particles assembled in the nucleus of the epithelial cells, apparently being synthesized de novo in association with a putative virogenic stroma, and they moved into the lumen of the ovarioles surrounding the developing eggs. VLPs were also found in some other cells in both male and female M. aethiopoides. VLPs have not been found in M. hyperodae or the New Zealand native species M. zealandicus. The function of the VLP and its possible role in potential parasitoid host range determination are discussed. Copyright 1999 Academic Press.

This article provides an innovative defence of co-determination by way of exploring two of the most significant theorised objections to it from neo-liberal and libertarian perspectives, namely, the defence of the right to manage as freely chosen by employees and employers alike, and the right to manage being the most efficient, lowest transaction cost mode of employee governance. Instead, we focus upon management preference emanating from the endowment effect, and manifested in management style and ideology, as a more credible explanation for management’s support for its prerogative to manage. The endowment effect prompts both strong employer and manager objections to co-determination and weak employee willingness to seek it because humans place more value upon items currently in their possession than upon those they do not possess. We explore this argument by examining the experience of co-determination in Germany. The significance of our argument lies in identifying managerial preference as the key variable to be challenged and changed in order to pacify management opposition to co-determination through political, ideological and institutional means.

Signals of dominance and fighting ability (i.e. status signals) are found in a wide range of taxa and are used to settle disputes between competitive rivals. Most previous research has considered status-signal phenotype as an attribute of the individual; however, it is more likely that signal expression is an emergent property that also incorporates aspects of the social environment. Furthermore, because an individual's signal phenotype is likely to influence its social interactions, the relationships between status signals, social environment and individual quality are probably much more complex than previously appreciated. Here, we explore the dynamic relationship between social interactions and signal expression in a previously undescribed status signal, the frontal shield of the pukeko ( Porphyrio porphyrio melanotus : Aves). We demonstrate that frontal shield size is a strong predictor of dominance status within social groups, even after controlling for potentially confounding variables. Then, we evaluate the relationship between social interactions and signal expression by testing whether manipulating apparent shield size influences (i) dominance interactions and (ii) future signal expression. By showing that decreasing apparent shield size causes both an increase in the amount of aggression received and a decrease in an individual's true shield size, we provide the first evidence of dynamic feedback between signal expression and social interactions. Our study provides important insight into the role of receiver-dependent (i.e. social) costs in maintaining signal honesty and demonstrates a unique approach to studying status signalling applicable to future studies on dynamic morphological signals.

Administering intramammary antimicrobials to all mammary quarters of dairy cows at drying-off [i.e., blanket dry cow therapy (BDCT)] has been a mainstay of mastitis prevention and control. However, as udder health has considerably improved over recent decades with reductions in intramammary infection prevalence at drying-off and the introduction of teat sealants, BDCT may no longer be necessary on all dairy farms, thereby supporting antimicrobial stewardship efforts. This narrative review summarizes available literature regarding current dry cow therapy practices and associ-ated impacts of selective dry cow therapy (SDCT) on udder health, milk production, economics, antimicro-bial use, and antimicrobial resistance. Various methods to identify infections at drying-off that could benefit from antimicrobial treatment are described for select-ing cows or mammary quarters for treatment, includ-ing utilizing somatic cell count thresholds, pathogen identification, previous clinical mastitis history, or a combination of criteria. Selection methods may be enacted at the herd, cow, or quarter levels. Producers' and veterinarians' motivations for antimicrobial use are discussed. Based on review findings, SDCT can be ad-opted without negative consequences for udder health and milk production, and concurrent teat sealant use is recommended, especially in udder quarters receiving no intramammary antimicrobials. Furthermore, herd selection should be considered for SDCT implementa-tion in addition to cow or quarter selection, as BDCT may still be temporarily necessary in some herds for optimal mastitis control. Costs and benefits of SDCT vary among herds, whereas impacts on antimicrobial resistance remain unclear. In summary, SDCT is a vi-able management option for maintaining udder health and milk production while improving antimicrobial stewardship in the dairy industry.

Abstract Background Best practice for prevention, diagnosis, and management of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID‐19) is unknown due to limited published data in this population. Objectives We aimed to assess current global practice and experience in management of COVID‐19–associated coagulopathy to identify information to guide prospective and randomized studies. Methods Physicians were queried about their current approach to prophylaxis, diagnosis, and treatment of VTE in patients with COVID‐19 using an online survey tool distributed through multiple international organizations between April 10 and 14, 2020. Results Five hundred fifteen physicians from 41 countries responded. The majority of respondents (78%) recommended prophylactic anticoagulation for all hospitalized patients with COVID‐19, with most recommending use of low‐molecular‐weight heparin or unfractionated heparin. Significant practice variation was found regarding the need for dose escalation of anticoagulation outside the setting of confirmed or suspected VTE. Respondents reported the use of bedside testing when unable to perform standard diagnostic imaging for diagnosis of VTE. Two hundred ninety‐one respondents reported observing thrombotic complications in their patients, with 64% noting that the complication was pulmonary embolism. Of the 44% of respondents who estimated incidence of thrombosis in patients with COVID‐19 in their hospital, estimates ranged widely from 1% to 50%. One hundred seventy‐four respondents noted bleeding complications (34% minor bleeding, 14% clinically relevant nonmajor bleeding, and 12% major bleeding). Conclusion Well‐designed epidemiologic studies are urgently needed to understand the incidence and risk factors of VTE and bleeding complications in patients with COVID‐19. Randomized clinical trials addressing use of anticoagulation are also needed.

The ileal energy contribution of protein, starch, and fat in response to 2 exogenous enzyme combinations was studied in 2 digestibility assays with 21- (experiment 1; 432 birds) and 42-d-old (experiment 2; 288 birds) Ross 308 broiler chickens. A 2 × 2 × 3 factorial arrangement of treatments with 2 base grains (corn or wheat), without or with high fiber ingredients (corn distillers dried grains with solubles and canola meal), and 3 enzyme treatments was implemented. Enzyme treatments, fed from 12 to 21 d or 32 to 42 d, were 1) without enzymes, 2) with xylanase from Trichoderma ressei (2,000 U/kg) and amylase from Bacillus licheniformis (200 U/kg; XA), or 3) with XA plus protease from Bacillus subtilis (4,000 U/kg; XAP). All diets contained Escherichia coli phytase (500 FTU/kg). Apparent ileal digestibility (AID) of protein, starch, and fat, as well as the apparent ileal digestible energy, were determined using titanium dioxide as inert marker. A generalized mixed model was used to test main effects and 2-way interactions at P < 0.05. An enzyme × grain interaction was detected for AID of starch at 21 and 42 d, and AID of fat at 21 d, with greater effects of enzymes in wheat-based compared with corn-based diets, but significant increments due to enzymes compared with controls in both diet types. Apparent ileal digestibility of fat at 42 d increased with enzyme supplementation compared with the control treatments. The XA and XAP treatments gradually (P < 0.05) increased AID of protein at 21 d, but only XAP increased AID of protein compared with the control at 42 d. Compared with the controls, XA increased AID energy by 52 or 87 kcal, and XAP by 104 or 152 kcal/kg of DM at 21 or 42 d, respectively. The caloric contribution of starch, fat, and protein were affected differentially by base grain and the presence of fibrous ingredients at 21 and 42 d of age.