Astrophysicists distinguish between three different kinds of compact stars. These are white dwarfs, neutron stars, and black holes. The former contain matter in one of the densest forms found in the ...Universe which, together with the unprecedented progress in observational astronomy, makes such stars superb astrophysical laboratories for a broad range of most striking physical phenomena. These range from nuclear processes on the stellar surface to processes in electron degenerate matter at subnuclear densities to boson condensates and the existence of new states of baryonic matter—such as color superconducting quark matter—at supernuclear densities. More than that, according to the strange matter hypothesis strange quark matter could be more stable than nuclear matter, in which case neutron stars should be largely composed of pure quark matter possibly enveloped in thin nuclear crusts. Another remarkable implication of the hypothesis is the possible existence of a new class of white dwarfs. This article aims at giving an overview of all these striking physical possibilities, with an emphasis on the astrophysical phenomenology of strange quark matter. Possible observational signatures associated with the theoretically proposed states of matter inside compact stars are discussed as well. They will provide most valuable information about the phase diagram of superdense nuclear matter at high baryon number density but low temperature, which is not accessible to relativistic heavy ion collision experiments.
Cytokine storm and sepsis disease pathogenesis Chousterman, Benjamin G.; Swirski, Filip K.; Weber, Georg F.
Seminars in immunopathology,
07/2017, Letnik:
39, Številka:
5
Journal Article
Recenzirano
Infectious diseases are a leading cause of death worldwide. Sepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade ...that will lead to an autoamplifying cytokine production: the cytokine storm. Cytokines are a broad category of relatively small proteins (<40 kDa) that are produced and released with the aim of cell signaling. Our understanding of the processes that trigger this tremendous amount of cytokine production has made dramatic progress over the last decades, but unfortunately, these findings could not translate yet into effective treatments; so far, all clinical trials targeting cytokine production or effects failed. This review aims to summarize the pathophysiology of the cytokine storm; to describe the type, effects, and kinetics of cytokine production; and to discuss the therapeutic challenges of targeting cytokines. New promising therapeutic strategies focusing on the endothelium, as a source and a target of cytokines, are described.
Highlights ► The suppression of cancer metastasis is an urgent therapeutic need. ► Drugs that inhibit the dissemination of malignant cells will be broadly beneficial. ► The risk tolerance in drug ...trials needs to increase with a worsening prognosis. ► Clinical trials of drug molecules that prevent cancer dissemination need to be approved for use right after diagnosis. ► For agents that treat existing metastases, the clinical trial system needs to be modernized.
We aimed to determine the effect of hospital volume on in-hospital mortality, and failure to rescue following major pancreatic resections using hospital discharge data of every inpatient case in ...Germany.
Several studies have found strong volume-outcome relationships in pancreatic surgery, with high mortality in low-volume facilities. However, their datasets were only based on portions of national populations. In addition, these studies did not assess the effect of hospital volume according to other crucial variables such as medical indications, postoperative complications, and failure to rescue.
We studied all inpatient cases of major pancreatic surgery (n = 60,858) in Germany from 2009 to 2014, using national hospital discharge data. We evaluated the association between hospital volume and in-hospital mortality following major pancreatic resections by using multivariate regression methods. In addition, we analyzed rates of major complications and failure to rescue across hospital volume quintiles.
Risk-adjusted in-hospital mortality varied widely across hospital volume quintiles, from 6.5% (95% CI 6.0-7.0) in very high volume hospitals to 11.5% (95% CI 10.9-12.1) in very low volume hospitals (OR 0.47, 95% CI 0.41-0.54). Rates of postoperative interventions necessary for complications and failure to rescue were lower in higher volume hospitals eg, mortality following septic complications in very high volume hospitals: 24.2% (95% CI 22.4-26.1) vs. very low volume hospitals: 36.8% (34.9-38.7). Moreover, we estimated that centralization of surgical care to the minimum volume and mortality risk of the medium volume quintile could prevent at least 94 deaths per year.
In Germany, patients who are undergoing major pancreatic resections have improved outcomes if they are admitted to higher volume hospitals. As current health policies failed to centralize pancreatic surgery procedures in Germany, new strategies to initiate a sufficient centralization process in the field of pancreatic surgery are needed.
Collective cell migration requires maintenance of adhesive contacts between adjacent cells, coordination of polarized cell protrusions, and generation of propulsive traction forces. We demonstrate ...that mechanical force applied locally to C-cadherins on single Xenopus mesendoderm cells is sufficient to induce polarized cell protrusion and persistent migration typical of individual cells within a collectively migrating tissue. Local tension on cadherin adhesions induces reorganization of the keratin intermediate filament network toward these stressed sites. Plakoglobin, a member of the catenin family, is localized to cadherin adhesions under tension and is required for both mechanoresponsive cell behavior and assembly of the keratin cytoskeleton at the rear of these cells. Local tugging forces on cadherins occur in vivo through interactions with neighboring cells, and these forces result in coordinate changes in cell protrusive behavior. Thus, cadherin-dependent force-inducible regulation of cell polarity in single mesendoderm cells represents an emergent property of the intact tissue.
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► Tensile force on cadherins induces polarity of migration in the opposite direction ► Keratin filaments and plakoglobin are recruited to mechanically stimulated cadherins ► Keratin and plakoglobin are required for mechanoresponsive cell behavior
Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the most severe coronavirus (CoV)-associated diseases in humans. The causative agents, SARS-CoV and MERS-CoV, ...are of zoonotic origin but may be transmitted to humans, causing severe and often fatal respiratory disease in their new host. The two coronaviruses are thought to encode an unusually large number of factors that allow them to thrive and replicate in the presence of efficient host defense mechanisms, especially the antiviral interferon system. Here, we review the recent progress in our understanding of the strategies that highly pathogenic coronaviruses employ to escape, dampen, or block the antiviral interferon response in human cells.
Cancer care represents a substantial and rapidly rising healthcare cost in Australia. Our aim was to provide accurate population-based estimates of the health services cost of cancer care using ...large-scale linked patient-level data.
We analysed data for incident cancers diagnosed 2006-2010 and followed to 2014 among 266,793 eligible participants in the 45 and Up Study. Health system costs included Medicare and pharmaceutical claims, inpatient hospital episodes and emergency department presentations. Costs for cancer cases and matched cancer-free controls were compared, to estimate monthly/annual excess costs of cancer care by cancer type, before and after diagnosis and by phase of care (initial, continuing, terminal). Total costs incurred in 2013 were also estimated for all people diagnosed in Australia 2009-2013.
7624 participants diagnosed with cancer were matched with up to three controls. The mean excess cost of care per case was AUD$1,622 for the year before diagnosis, $33,944 for the first year post-diagnosis and $8,796 for the second year post-diagnosis, with considerable variation by cancer type. Mean annual cost after the initial treatment phase was $4,474/case and the mean cost for the last year of life was $49,733/case. In 2013 the cost for cancers among people in Australia diagnosed during 2009-2013 was ~$6.3billion (0.4% of Gross Domestic Product; $272 per capita), with the largest costs for colorectal cancer ($1.1billion), breast cancer ($0.8billion), lung cancer ($0.6billion) and prostate cancer ($0.5billion).
The cost of cancer care is substantial and varies by cancer type and time since diagnosis. These findings emphasise the economic importance of effective primary and secondary cancer prevention strategies.
We aimed to determine the unbiased mortality rates for pancreatic surgery procedures at the national level through a comprehensive analysis of every inpatient case in Germany.
Several studies have ...proclaimed a general improvement of perioperative outcomes following pancreatic surgery. These results are challenged by recent analyses of large US databases that found strong volume-outcome relationships, with high mortality in low-volume facilities.
All inpatient cases with a pancreatic surgery procedure code in Germany from 2009 to 2013 were identified from nationwide administrative hospital data. We determined the absolute number of patients and the in-hospital death rate for crucial subcategories such as medical indications and types of surgical procedure.
A total of 58,003 inpatient episodes of pancreatic surgery were identified between 2009 and 2013. Annual case numbers increased significantly, which was primarily attributed to patients aged 70 years and older. The overall in-hospital mortality rate (10.1%) did not significantly change during the study period. Major pancreatic resections were associated with mortality ranging from 7.3% (distal pancreatectomy) to 22.9% (total pancreatectomy). Postoperative interventions indicative of severe complications were documented frequently (eg, more than 6 blood transfusions in 20% of all patients and relaparotomy in 16%). Their occurrence was associated with a dramatic increase in mortality.
At the national level in Germany, perioperative mortality is higher than anticipated from previous studies. The absence of a significant reduction in overall mortality challenges current health policies that aim to improve the outcomes of high-risk surgical procedures in Germany.
Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. ...To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.
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