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Objectives: RESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context., Methods: This is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008-2016) and one from the Brain-IT study, a European multicenter database (2003-2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thiopental were analysed, as well as Extended Glasgow Outcome score (GOSE) at 6 months., Results: In the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recovery 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02)., Conclusion: Outcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing severe TBI., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We report the isolation of Equid herpesvirus 8 from a rescued donkey that suffered severe postcastration complications. Despite intensive treatment, the donkey deteriorated and was euthanized. Postmortem virologic analysis revealed the isolation of a herpesvirus that is closely related to herpesviruses reported from donkeys and horses in Australia, China, and Ireland, causing respiratory disease in donkeys and abortion in mares. To our knowledge, this is the first report of this equid herpesvirus in Israel. The potential significance of this herpesvirus to the equid population in Israel needs further investigation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

What criteria are most suitable to identify endocrine disrupting substances (EDSs) for regulatory purposes in the EU? The results of the European Commission's public consultation, as part of the process to establish identification criteria for EDSs, show that different regulatory options are supported. Some respondents prefer an option including hazard characterization considerations, whereas others prefer an option that avoids these considerations and introduces several hazard-identification based weight-of-evidence categories. In this study, the argumentation underlying the different preferences for identification criteria are analyzed and compared using pragma-dialectical argumentation theory (PDAT). All responses of non-anonymous, national governments that submitted a response in English (n = 17) were included. Responses of other stakeholder organizations were included if a Google News search returned an opinionated presence in the media on the subject (n = 9). Five topical themes and 21 underlying issues were identified. The themes are 1) mechanistic understanding of EDSs, 2) regulatory considerations related to the identification of EDSs, 3) consistency with existing regulatory frameworks, and 4) evaluations of specific issues related to a category approach and 5) related to including potency. We argue that two overarching (implicit) 'advocacy coalitions' can be discerned, that adopted contrasting positions towards the identified themes and issues. Among these 'coalitions', there appears to be consensus about the necessity of having 'science-based' criteria, though different perspectives exist as to what the most accurate mechanistic understanding of EDSs entails. To move the discussion forward, we argue that a societal dialogue would be beneficial, where EDS science and regulation are discussed as interrelated themes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Following an infection, cytokines not only regulate the acute immune response, but also contribute to symptoms such as inflammatory hyperalgesia. We aimed to characterize the acute inflammatory response induced by a human endotoxemia model, and its effect on pain perception using evoked pain tests in two different dose levels. We also attempted to determine whether combining a human endotoxemia challenge with measurement of pain thresholds in healthy subjects could serve as a model to study drug effects on inflammatory pain., Methods and Results: This was a placebo-controlled, randomized, cross-over study in 24 healthy males. Twelve subjects were administered a bolus of 1 ng/kg LPS intravenously, and twelve 2 ng/kg LPS. Before days of placebo/LPS administration, subjects completed a full study day without study drug administration, but with identical pain threshold testing. Blood sampling and evoked pain tests (electrical burst and -stair, heat, pressure, and cold pressor test) were performed pre-dose and at frequent intervals up to 10hr post-dose. Data were analysed with a repeated-measures ANCOVA. For both dose levels, LPS induced an evident acute inflammatory response, but did not significantly affect any of the pain modalities. In a post-hoc analysis, lowering of pain thresholds was observed in the first 3 h after dosing, corresponding with the peak of the acute inflammatory response around 1-3 h post-dose., Conclusion: Mild acute systemic inflammation, as induced by 1 ng/kg and 2 ng/kg LPS intravenous administration, did not significantly change pain thresholds in this study. The endotoxemia model in combination with evoked pain tests is not suitable to study acute inflammatory hyperalgesia in healthy males., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recognition of the widespread use of the word 'mechanism' in bio-molecular research has resulted in the concept of 'mechanism' becoming a focal point for a highly visible group of philosophers of biology. Rather, however, than grasping and elucidating the situated aims and practices of biologists themselves, the philosophical investigation of the contemporary meaning of mechanism in biology has been commandeered by the needs of 'hard naturalists' to replace the old deductive-nomological model of the 'received view' with a new normative-explanatory gold-standard. It is argued that rather than an orientation toward an increasingly precise characterization of mechanisms as being an ultimate end in biological research, in actual biological practice 'mechanism' means different things in different contexts, pragmatically draws on our embodied know-how in the use of machines and is not, nor should be, an ultimate end of biological research. Further, it is argued, that classic work on low-level mechanisms became taken up qualitatively as parts of the scaffolding for investigating higher level regulatory processes and that in so doing, and in light of new findings such as that of the regulatory significance of 'pleiomorphic ensembles' and 'intrinsically unstructured proteins' the explanatory limits of the mechanism image have already come into view., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To estimate the number of unlicensed brothels operating in Melbourne, Australia, and the sexual health of the women working in them., Methods: Advertisements from Melbourne newspapers published in July 2006 were systematically analysed based on the language used to identify premises likely to be unlicensed brothels. A visit was made to each of the businesses where an address was available. Participating sex workers were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis using self-collected tampons and polymerase chain reaction., Results: There were 438 advertisements collated, representing 174 separate establishments. Of these, 78 were not considered likely to be brothels. Of the remaining 96, addresses were available for 42 and all of these premises were visited. Thirteen were confirmed as unlicensed brothels. We estimate there were between 13 and 70 unlicensed brothels in Melbourne. Twenty-three women were recruited from four brothels. Only 56% (95% confidence interval (CI) 35-77%) reported having regular sexual health checks and only 13% (95%CI 3-36%) reported prior testing for HIV. Among the 22 women tested, one had chlamydia while another had gonorrhoea, a prevalence of 4.5% (95%CI: 2.3-20.4%) for each infection., Conclusions: The number of unlicensed brothels in Melbourne is much smaller than is generally believed. Women in the sector are infrequently tested for STIs., Implications: As long as a licensing system persists, promotion of sexual health among women in this sector is likely to face hurdles. Further research is needed into the best model for regulating or not regulating sex industries., (© 2010 The Authors. Journal Compilation © 2010 Public Health Association of Australia.)

The order Microsporidia contains a number of ubiquitous pathogens that can infect various animals, including humans. Enterocytozoon bieneusi and Encephalitozoon intestinalis have been associated with gastrointestinal illness in humans. The effect of four disinfectants--ammonium hydroxide, hydrogen peroxide, and two commercial disinfectants containing peroxyacetic acid (Tsunami) and N-alkyl dimethyl benzyl ammonium chloride (Timsen)--on E. intestinalis spores was examined using exposure times of 1, 5, and 15 min. Spore viability was determined in vitro with RK-13 cells. Hydrogen peroxide was most efficient at inactivating microsporidial spores at all tested concentrations and treatment times, whereas ammonium hydroxide was effective only at the highest concentration at all exposure times. Tsunami (40 microg/ml) and Timsen (200 and 400 ppm) could inactivate spores when incubated for 5 and 15 min.

Endothelial cells respond to vascular endothelial growth factor (VEGF) to produce new blood vessels. This process of angiogenesis makes a critical contribution during embryogenesis and also in the response to ischemia in adult tissues. We have studied the intracellular trafficking of the major VEGF receptor KDR (VEGFR2). Unlike other related growth factor receptors, we find that a significant proportion of KDR is held in an endosomal storage pool within endothelial cells. We find that KDR can be delivered to the plasma membrane from this intracellular pool and that VEGF stimulates this recycling to the cell surface. KDR recycling appears to be distinct from the previously characterized Rab4- and Rab11-dependent pathways, but, instead, KDR(+) recycling vesicles contain Src tyrosine kinase and VEGF-stimulated recycling requires Src activation. Taken together, these data show that intracellular trafficking of KDR is markedly different from other receptor tyrosine kinases and suggest that the regulation of KDR trafficking by VEGF provides a novel mechanism for controlling the sensitivity of endothelial cells to proangiogenic signals.

Background: In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people. The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics., Methods: We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays., Findings: A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs., Interpretation: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.

Relationships among nutritional status and skeletal and respiratory muscle function were examined in 16 children with cystic fibrosis (CF) and mild lung disease (FEV1 95 +/- 16% predicted). Subjects were randomly assigned to receive (or not) noninvasive nutritional supplementation at 25% of normal energy recommendations for 6 mo. Skeletal muscle strength and power were similar to those of healthy children as were respiratory muscle strength and endurance. Stepwise-regression analysis indicated that changes in skeletal muscle strength and energy intake correlated significantly with growth [weight (kg) = 1.90 - 0.60 (Tanner Stage) + 0.49 (maximum voluntary strength (Nm) + 0.03 (energy intake, % RNI), r = 0.76, P < 0.05], though body composition, protein biochemistry, muscle power, respiratory muscle strength, and use of dietary supplements did not. Thus, changes in skeletal muscle strength may be a functional index of changes in nutritional status in CF. Dietary supplementation per se was not associated with functional improvement.

A one-stage flap repair is described for complicated dorsal injuries of the hand involving loss of skin and tendon based on the principle of the "Chinese" radial artery forearm flap in which vascularised tendons are transferred to reconstruct the missing extensor tendons.

This is a case report of a congenital hemangioendothelioma-a rare vascular tumor of the hand. The literature concerning hemangioendothelioma has numerous conflicting statements as to histologic definition, malignant potential, and optimal treatment. A newborn found to have a hemangiomatous type of lesion on the index finger of the right hand was operated upon at 7 days of age. An intraoperative brachial arteriogram identified the radial digital artery as the major arterial supply to the lesion. The operating microscope allowed precise dissection and preservation of the digital nerves and the flexor and extensor tendons. The defect was covered with a full-thickness skin graft providing optimal follow-up for local recurrence.

An assay method for ATP-sulfurylase is described, based on the incorporation of 35SO4(2-) into adenosine-5'-phosphosulfate (and 3-phosphoadenosine-5'-phosphosulfate) and the separation of these compounds by HPLC. Since the enzyme is easily inactivated at temperatures above 20 degrees C during the assay, the reaction time should not exceed 10 min.

Effects of body size on the kinetics of glucose metabolism were examined. In trial 1, steers were fed 6 kg of an 80:20 concentrate:roughage diet daily across a weight range of 226 to 470 kg. In trial 2, steers were fed 4.5 kg of a 45:55 concentrate:roughage diet daily across a weight range of 134 to 390 kg. Glucose irreversible loss averaged 820 +/- 32 and 461 +/- 13 mg/min for trials 1 and 2 and was not affected by body size. Thus, glucose irreversible loss seems to be regulated by feed intake when intake is above maintenance. Body size had no effect on glucose total entry rate, recycling or pool size. Blood glucose concentration and glucose space decreased at 0.004 mg X ml-1 X kg-1 and 0.002 fractional units body wt X kg-1 as body size increased. Digestible energy and nitrogen balance were measured in trial 2. Digestibility of energy increased at 0.0054 Mcal X d-1 X kg-1 as body size increased. Nitrogen retention averaged 28.2 g X d-1 and was not influenced by body size even though energy intake approached maintenance amounts at the end of the trial. On the basis of urinary nitrogen excretion data, we conclude that the maximum net contribution of amino acid carbon to glucose synthesis was 8% of glucose carbon.