Safety and Efficacy of Erythropoietin in Traumatic Brain Injury Patients: A Pilot Randomized Trial

Background. Erythropoietin (EPO) is a neuroprotective agent utilized in stroke patients. This pilot study represents the first randomized trial of EPO in traumatic brain injury (TBI) patients. Methods. Adult, blunt trauma patients with evidence of TBI were randomized to EPO or placebo within 6 hours of injury. Baseline and daily serum S-100B and Neuron Specific Enolase (NSE) levels were measured. Results. TBI was worse in the EPO (n = 11) group compared to placebo patients (n = 5). The use of EPO did not impact NSE (P = .89) or S100 B (P = .53) levels compared to placebo. Conclusions. At the dose used, EPO did not reduce neuronal cell death compared to placebo; however, TBI severity was worse in the EPO group while levels of NSE and S100-B were similar to the less injured placebo group making it difficult to rule out a treatment effect. A larger, balanced study is necessary to confirm a potential treatment effect

Integrating Palliative Care Into the Care of Neurocritically Ill Patients: A Report From the Improving Palliative Care in the ICU Project Advisory Board and the Center to Advance Palliative Care

OBJECTIVES: To describe unique features of neurocritical illness that are relevant to provision of high-quality palliative care; to discuss key prognostic aids and their limitations for neurocritical illnesses; to review challenges and strategies for establishing realistic goals of care for patients in the neuro-ICU; and to describe elements of best practice concerning symptom management, limitation of life support, and organ donation for the neurocritically ill. DATA SOURCES: A search of PubMed and MEDLINE was conducted from inception through January 2015 for all English-language articles using the term palliative care, supportive care, end-of-life care, withdrawal of life-sustaining therapy, limitation of life support, prognosis, or goals of care together with neurocritical care, neurointensive care, neurological, stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or brain injury. DATA EXTRACTION AND SYNTHESIS: We reviewed the existing literature on delivery of palliative care in the neurointensive care unit setting, focusing on challenges and strategies for establishing realistic and appropriate goals of care, symptom management, organ donation, and other considerations related to use and limitation of life-sustaining therapies for neurocritically ill patients. Based on review of these articles and the experiences of our interdisciplinary/interprofessional expert advisory board, this report was prepared to guide critical care staff, palliative care specialists, and others who practice in this setting. CONCLUSIONS: Most neurocritically ill patients and their families face the sudden onset of devastating cognitive and functional changes that challenge clinicians to provide patient-centered palliative care within a complex and often uncertain prognostic environment. Application of palliative care principles concerning symptom relief, goal setting, and family emotional support will provide clinicians a framework to address decision making at a time of crisis that enhances patient/family autonomy and clinician professionalism

The Nucleosome (Histone-DNA Complex) Is the TLR9-Specific Immunostimulatory Component of Plasmodium falciparum That Activates DCs

The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. We recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (DCs) by TLR9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. We also demonstrated that DNA is the active constituent and that formation of a DNA-protein complex is essential for the entry of parasite DNA into cells for recognition by TLR9. However, the nature of endogenous protein-DNA complex in the parasite is not known. In this study, we show that parasite nucleosome constitute the major protein-DNA complex involved in the activation of DCs by parasite nuclear material. The parasite components were fractionated into the nuclear and non-nuclear materials. The nuclear material was further fractionated into chromatin and the proteins loosely bound to chromatin. Polynucleosomes and oligonucleosomes were prepared from the chromatin. These were tested for their ability to activate DCs obtained by the FLT3 ligand differentiation of bone marrow cells from the wild type, and TLR2−/−, TLR9−/− and MyD88−/− mice. DCs stimulated with the nuclear material and polynucleosomes as well as mono- and oligonucleosomes efficiently induced the production of proinflammatory cytokines in a TLR9-dependent manner, demonstrating that nucleosomes (histone-DNA complex) represent the major TLR9-specific DC-immunostimulatory component of the malaria parasite nuclear material. Thus, our data provide a significant insight into the activation of DCs by malaria parasites and have important implications for malaria vaccine development

Izloženost alergenima plijesni u unutarnjem okolišu

Humid indoor environments may be colonised by allergenic fi lamentous microfungi (moulds), Aspergillus spp., Penicillium spp., Cladosporium spp., and Alternaria spp. in particular. Mould-induced respiratory diseases are a worldwide problem. In the last two decades, mould allergens and glucans have been used as markers of indoor exposure to moulds. Recently, mould allergens Alt a 1 (Alternaria alternata) and Asp f 1 (Aspergillus fumigatus) have been analysed in various environments (residential and occupational) with enzyme-linked immunosorbent assays, which use monoclonal or polyclonal antibodies. Household Alt a 1 and Asp f 1 levels were usually under the limit of the method detection. By contrast, higher levels of mould allergens were found in environments with high levels of bioaerosols such as poultry farms and sawmills. Data on allergen Alt a 1 and Asp f 1 levels in agricultural settings may provide information on possible colonisation of respective moulds and point out to mould-related diseases in occupants.Vlažni, unutarnji prostori mogu biti kolonizirani alergogenim, filamentoznim mikrogljivicama (plijesni) uglavnom rodova Aspergillus, Penicillium, Cladosporium i Alternaria. Respiratorne bolesti uzrokovane plijesnima zdravstveni su problem diljem svijeta. U posljednja dva desetljeća, neki sastavni dijelovi plijesni kao alergeni i glukan rabe se kao pokazatelji izloženosti plijesni u unutarnjem okolišu. Nedavno su alergeni plijesni Alt a 1 (Alternaria alternata) i Asp f 1 (Aspergillus fumigatus) određivani u različitom okolišu (kućnom i profesionalnom) enzim-imunokemijskom metodom koja rabi monoklonska ili poliklonska antitijela. Razina Alt a 1 i Asp f 1 u kućnoj prašini ispod je granice detekcije. Nasuprot tomu, alergeni plijesni su određeni u okolišu s visokom razinom bioaerosola kao peradarnici i pilane. Razine alergena Alt a 1 i Asp f 1 u nekim poljoprivrednim objektima pružaju informaciju o mogućoj kolonizaciji plijesnima, što upućuje na moguće zdravstvene učinke kod zaposlenika

Female Audit Partners and Extended Audit Reporting: UK Evidence

This study investigates whether audit partner gender is associated with the extent of auditor disclosure and the communication style regarding risks of material misstatements that are classified as key audit matters (KAMs). Using a sample of UK firms during the 2013–2017 period, our results suggest that female audit partners are more likely than male audit partners to disclose more KAMs with more details after controlling for both client and audit firm attributes. Furthermore, female audit partners are found to use a less optimistic tone and provide less readable audit reports, compared to their male counterparts, suggesting that behavioural variances between female and male audit partners may have significant implications on their writing style. Therefore, this study offers new insights on the role of audit partner gender in extended audit reporting. Our findings have important implications for audit firms, investors, policymakers and governments in relation to the development, implementation and enforcement of gender diversity

Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19

Free abdominal fluid without obvious solid organ injury upon CT imaging: an actual problem or simply over-diagnosing?

Whereas a non-operative approach for hemodynamically stable patients with free intraabdominal fluid in the presence of solid organ injury is generally accepted, the presence of free fluid in the abdomen without evidence of solid organ injury not only presents a challenge for the treating emergency physician but also for the surgeon in charge. Despite recent advances in imaging modalities, with multi-detector computed tomography (CT) (with or without contrast agent) usually the imaging method of choice, diagnosis and interpretation of the results remains difficult. While some studies conclude that CT is highly accurate and relatively specific at diagnosing mesenteric and hollow viscus injury, others studies deem CT to be unreliable. These differences may in part be due to the experience and the interpretation of the radiologist and/or the treating physician or surgeon