Outcomes after pneumonectomy versus limited lung resection in adults with traumatic lung injury.

Pneumonectomy after traumatic lung injury (TLI) is associated with shock, increased pulmonary vascular resistance, and eventual right ventricular failure. Historically, trauma pneumonectomy (TP) mortality rates ranged between 53 and 100%. It is unclear if contemporary mortality rates have improved. Therefore, we evaluated outcomes associated with TP and limited lung resections (LLR) (i.e., lobectomy and segmentectomy) and aimed to identify predictors of mortality, hypothesizing that TP is associated with greater mortality versus LLR. We queried the Trauma Quality Improvement Program (2010-2016) and performed a multivariable logistic regression to determine the independent predictors of mortality in TLI patients undergoing TP versus LLR. TLI occurred in 287,276 patients. Of these, 889 required lung resection with 758 (85.3%) undergoing LLR and 131 (14.7%) undergoing TP. Patients undergoing TP had a higher median injury severity score (26.0 vs. 24.5, p = 0.03) but no difference in initial median systolic blood pressure (109 vs. 107 mmHg, p = 0.92) compared to LLR. Mortality was significantly higher for TP compared to LLR (64.9% vs 27.2%, p < 0.001). The strongest independent predictor for mortality was undergoing TP versus LLR (OR 4.89, CI 3.18-7.54, p < 0.001). TP continues to be associated with a higher mortality compared to LLR. Furthermore, TP is independently associated with a fivefold increased risk of mortality compared to LLR. Future investigations should focus on identifying parameters or treatment modalities that improve survivability after TP. We recommend that surgeons reserve TP as a last-resort management given the continued high morbidity and mortality associated with this procedure

The Ontology of Intentional Agency in Light of Neurobiological Determinism: Philosophy Meets Folk Psychology

The moot point of the Western philosophical rhetoric about free will consists in examining whether the claim of authorship to intentional, deliberative actions fits into or is undermined by a one-way causal framework of determinism. Philosophers who think that reconciliation between the two is possible are known as metaphysical compatibilists. However, there are philosophers populating the other end of the spectrum, known as the metaphysical libertarians, who maintain that claim to intentional agency cannot be sustained unless it is assumed that indeterministic causal processes pervade the action-implementation apparatus employed by the agent. The metaphysical libertarians differ among themselves on the question of whether the indeterministic causal relation exists between the series of intentional states and processes, both conscious and unconscious, and the action, making claim for what has come to be known as the event-causal view, or between the agent and the action, arguing that a sort of agent causation is at work. In this paper, I have tried to propose that certain features of both event-causal and agent-causal libertarian views need to be combined in order to provide a more defendable compatibilist account accommodating deliberative actions with deterministic causation. The ‘‘agent-executed-eventcausal libertarianism’’, the account of agency I have tried to develop here, integrates certain plausible features of the two competing accounts of libertarianism turning them into a consistent whole. I hope to show in the process that the integration of these two variants of libertarianism does not challenge what some accounts of metaphysical compatibilism propose—that there exists a broader deterministic relation between the web of mental and extra-mental components constituting the agent’s dispositional system—the agent’s beliefs, desires, short-term and long-term goals based on them, the acquired social, cultural and religious beliefs, the general and immediate and situational environment in which the agent is placed, etc. on the one hand and the decisions she makes over her lifetime on the basis of these factors. While in the ‘‘Introduction’’ the philosophically assumed anomaly between deterministic causation and the intentional act of deciding has been briefly surveyed, the second section is devoted to the task of bridging the gap between compatibilism and libertarianism. The next section of the paper turns to an analysis of folk-psychological concepts and intuitions about the effects of neurochemical processes and prior mental events on the freedom of making choices. How philosophical insights can be beneficially informed by taking into consideration folk-psychological intuitions has also been discussed, thus setting up the background for such analysis. It has been suggested in the end that support for the proposed theory of intentional agency can be found in the folk-psychological intuitions, when they are taken in the right perspective

Comparing continuous lumbar plexus block, continuous epidural block and continuous lumbar plexus block with a parasacral sciatic nerve block on post-operative analgesia after hip arthroplasty

Study Objective: To compare post-operative analgesia obtained by continuous lumbar epidural block (CLEB) versus continuous lumbar plexus block (CLPB) versus CLPB associated with a single shot parasacral sciatic nerve block (CLEBS) after total hip arthroplasty (THA). Study design: Randomized clinical trial. Setting: Operating room, postoperative care unit, orthopedic surgical ward. Methods: 78 ASA I-III patients undergoing elective THA were randomly assigned to receive CLEB (n=24, 15-20 ml of 5 mg/ml ropivacaine, sufentanil 10 mg, clonidine 1 mg/ml), CLPB (n=22, 3mg/kg of 5 mg/ml of ropivacaine, max. 40 ml, clonidine 1 mg/ml, sufentanil 10 mg) or CLPBS (n=23, CLPB as described above; sciatic nerve: 20 ml of ropivacaine 5 mg/ml, clonidine 1 mg/ml). All patients received continuous infusion of 2 mg/ml of ropivacaine, 8 ml/h for 48 hours. Primary outcome was pain intensity assessment (VAS and VS). Secondary outcomes were postoperative total opioid consumption, hemodynamic stability, motor blockade, blood loss, intraoperative sufentanil and propofol consumption, patient satisfaction and complications. Results: VAS was lower in the CLEB group than in the CLPB and CLPBS groups respectively for 6 and 12 hours postoperatively (post-surgery p<0.001, 2h p<0.001, 6h p<0.001, 12h p<0.03)(Table 2). Moreover, CLPSB patients reported lower VAS than CLPB patients from the end of the surgery till the 12th follow up hour (Table 2). VS was lower in the CLEB group from the end of surgery to 6h postoperatively (Table 3). The CLPB group showed higher morphine consumption than the CLPSB and CLEB groups over 12 h postoperatively (p=0.05); thereafter, no statistically significant diferences were observed between groups at the end of follow up (48h) (p=0.4) (Table 4). onclusion: In conclusion, continuous lumbar plexus block in association with single shot sciatic nerve block is a valid alternative to epidural technique in managing postoperative analgesia after THA, with an improved risk-benefit balanc

Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction

Microfluidic organ-on-a-chip technology aims to replace animal toxicity testing, but thus far has demonstrated few advantages over traditional methods. Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity, as well as pluripotency and disease processes. However, current methods to evaluate mitochondrial activity still rely on end-point assays, resulting in limited kinetic and prognostic information. Here, we present a liver-on-chip device capable of maintaining human tissue for over a month in vitro under physiological conditions. Mitochondrial respiration was monitored in real time using two-frequency phase modulation of tissue-embedded phosphorescent microprobes. A computer-controlled microfluidic switchboard allowed contiguous electrochemical measurements of glucose and lactate, providing real-time analysis of minute shifts from oxidative phosphorylation to anaerobic glycolysis, an early indication of mitochondrial stress. We quantify the dynamics of cellular adaptation to mitochondrial damage and the resulting redistribution of ATP production during rotenone-induced mitochondrial dysfunction and troglitazone (Rezulin)-induced mitochondrial stress. We show troglitazone shifts metabolic fluxes at concentrations previously regarded as safe, suggesting a mechanism for its observed idiosyncratic effect. Our microfluidic platform reveals the dynamics and strategies of cellular adaptation to mitochondrial damage, a unique advantage of organ-on-chip technology

Service Level Constrained Inventory Systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151878/1/poms13060_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151878/2/poms13060.pd

A Novel Cellular Model to Study Angiotensin II AT2 Receptor Function in Breast Cancer Cells

Recent studies have highlighted the AT1 receptor as a potential therapeutic target in breast cancer, while the role of the AT2 subtype in this disease has remained largely neglected. The present study describes the generation and characterization of a new cellular model of human invasive breast cancer cells (D3H2LN-AT2) stably expressing high levels of Flag-tagged human AT2 receptor (Flag-hAT2). These cells exhibit high-affinity binding sites for AngII, and total binding can be displaced by the AT2-selective antagonist PD123319 but not by the AT1-selective antagonist losartan. Of interest, high levels of expression of luciferase and green fluorescent protein make these cells suitable for bioluminescence and fluorescence studies in vitro and in vivo. We provide here a novel tool to investigate the AT2 receptor functions in breast cancer cells, independently of AT1 receptor activation

Hepatoportal Venous Trauma: Analysis of Incidence, Morbidity, and Mortality.

ObjectivesAlthough traumatic injuries to the superior mesenteric vein (SMV), portal vein (PV), and hepatic vein (HV) are rare, their impact is significant. Small single center reports estimate mortality rates ranging from 29% to 100%. Our aim is to elucidate the incidence and outcomes associated with each injury due to unique anatomic positioning and varied tolerance of ligation. We hypothesize that SMV injury is associated with a lower risk of mortality compared to HV and PV injury in adult trauma patients.MethodsThe Trauma Quality Improvement Program database (2010-2016) was queried for patients with injury to either the SMV, PV, or HV. A multivariable logistic regression model was used for analysis.ResultsFrom 1,403,466 patients, 966 (0.07%) had a single major hepatoportal venous injury with 460 (47.6%) involving the SMV, 281 (29.1%) involving the PV, and 225 (23.3%) involving the HV. There was no difference in the percentage of patients undergoing repair or ligation between SMV, PV, and HV injuries (P &gt; .05). Compared to those with PV and HV injuries, patients with SMV injury had a higher rate of concurrent bowel resection (38.5% vs 12.1% vs 7.6%, P &lt; .001) and lower mortality (33.3% vs 45.9% vs 49.3%, P &lt; .01). After controlling for covariates, traumatic SMV injury increased the risk of mortality (odds ratio [OR] 1.59, confidence interval [CI] = 1.00-2.54, P = .05) in adult trauma patients; however, this was less than PV injury (OR = 2.77, CI = 1.56-4.93, P = .001) and HV injury (OR = 2.70, CI = 1.46-4.99, P = .002).ConclusionTraumatic SMV injury had a lower rate of mortality compared to injuries of the HV and PV. SMV injury increased the risk of mortality by 60% in adult trauma patients, whereas PV and HV injuries nearly tripled the risk of mortality

Multiple effects of silymarin on the hepatitis C virus lifecycle

Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. CONCLUSION: Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell

Challenges of tuberculosis management in high and low prevalence countries in a mobile world

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.In this issue of the PCRJ, Bishara et al. 1 present a case report about the treatment of a pregnant woman with tuberculosis (TB). She had emigrated from a country with a high prevalence of TB to one with a lower prevalence. This presented a challenge to her physicians who were faced with identifying and treating close contacts who were also infected. This Perspective article explores in more depth some of the questions raised by this case report. It discusses the role of primary care physicians in low prevalence countries who can implement evidence-based screening programmes, it discusses effective strategies for the diagnosis and treatment of TB in countries with high TB prevalence, and it presents insights from medical anthropology that can help practitioners overcome the barriers to TB diagnosis, treatment and screening described in the case report

An Agent-Based Approach to Self-Organized Production

The chapter describes the modeling of a material handling system with the production of individual units in a scheduled order. The units represent the agents in the model and are transported in the system which is abstracted as a directed graph. Since the hindrances of units on their path to the destination can lead to inefficiencies in the production, the blockages of units are to be reduced. Therefore, the units operate in the system by means of local interactions in the conveying elements and indirect interactions based on a measure of possible hindrances. If most of the units behave cooperatively ("socially"), the blockings in the system are reduced. A simulation based on the model shows the collective behavior of the units in the system. The transport processes in the simulation can be compared with the processes in a real plant, which gives conclusions about the consequencies for the production based on the superordinate planning.Comment: For related work see http://www.soms.ethz.c