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

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

Early psychological care of the French victims of the Costa Concordia shipwreck

Most of the French passengers who survived the shipwreck of the cruise ship Costa Concordia were repatriatedfrom Italy to Marseille, one of the stopovers of the cruise. The shipwreck happened during the nightof 13th–14th January 2012 and entailed the forced evacuation of 4195 passengers and crewmembers.Thirty-two persons died and 2 others are still reported missing. The massive and unexpected inflow of402 French citizens in the port of Marseille required the quick setting up of welcome facilities, not only tosolve logistical problems, but also to address psychological and sometimes even medical problems. ThePrehospital Psychological Emergency Service (CUMP) and the Prehospital Emergency Medical Service(SAMU) of Marseille examined 196 persons in total, and were able to avoid a great number of emergencyadmissions deemed necessary because of difficult psychological situations (death, missing or lost persons,acute stress). The objective of this report is to rapidly present the emergency committee as a whole andto describe in more detail the work that the CUMP accomplished during the 36 hours necessary to takecharge of the majority of the French passengers of the Costa Concordia.Most of the French passengers who survived the shipwreck of the cruise ship Costa Concordia were repatriatedfrom Italy to Marseille, one of the stopovers of the cruise. The shipwreck happened during the nightof 13th–14th January 2012 and entailed the forced evacuation of 4195 passengers and crewmembers.Thirty-two persons died and 2 others are still reported missing. The massive and unexpected inflow of402 French citizens in the port of Marseille required the quick setting up of welcome facilities, not only tosolve logistical problems, but also to address psychological and sometimes even medical problems. ThePrehospital Psychological Emergency Service (CUMP) and the Prehospital Emergency Medical Service(SAMU) of Marseille examined 196 persons in total, and were able to avoid a great number of emergencyadmissions deemed necessary because of difficult psychological situations (death, missing or lost persons,acute stress). The objective of this report is to rapidly present the emergency committee as a whole andto describe in more detail the work that the CUMP accomplished during the 36 hours necessary to takecharge of the majority of the French passengers of the Costa Concordia

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Modulation of pain perception by transcranial magnetic stimulation of left prefrontal cortex

Evidence by functional imaging studies suggests the role of left dorsolateral prefrontal cortex (DLPFC) in the inhibitory control of nociceptive transmission system. Repetitive transcranial magnetic stimulation (rTMS) is able to modulate pain response to capsaicin. In the present study, we evaluated the effect of DLPFC activation (through rTMS) on nociceptive control in a model of capsaicin-induced pain. The study was performed on healthy subjects that underwent capsaicin application on right or left hand. Subjects judged the pain induced by capsaicin through a 0–100 VAS scale before and after 5 Hz rTMS over left and right DLPFC at 10 or 20 min after capsaicin application in two separate groups (8 subjects each). Left DLPFC-rTMS delivered either at 10 and 20 min after capsaicin application significantly decreased spontaneous pain in both hands. Right DLPFC rTMS showed no significant effect on pain measures. According to these results, stimulation of left DLPFC seems able to exert a bilateral control on pain system, supporting the critical antinociceptive role of such area. This could open new perspectives to non-invasive brain stimulation protocols of alternative target area for pain treatment

Lignosulfonic Acid Exhibits Broadly Anti-HIV-1 Activity – Potential as a Microbicide Candidate for the Prevention of HIV-1 Sexual Transmission

Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA), a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs) and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide

Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity

Free Will & Empirical Arguments for Epiphenomenalism

While philosophers have worried about mental causation for centuries, worries about the causal relevance of conscious phenomena are also increasingly featuring in neuroscientific literature. Neuroscientists have regarded the threat of epiphenomenalism as interesting primarily because they have supposed that it entails free will scepticism. However, the steps that get us from a premise about the causal irrelevance of conscious phenomena to a conclusion about free will are not entirely clear. In fact, if we examine popular philosophical accounts of free will, we find, for the most part, nothing to suggest that free will is inconsistent with the presence of unconscious neural precursors to choices. It is only if we adopt highly non-naturalistic assumptions about the mind (e.g. if we embrace Cartesian dualism and locate free choice in the non-physical realm) that it seems plausible to suppose that the neuroscientific data generates a threat to free will

8p22 MTUS1 Gene Product ATIP3 Is a Novel Anti-Mitotic Protein Underexpressed in Invasive Breast Carcinoma of Poor Prognosis

BACKGROUND: Breast cancer is a heterogeneous disease that is not totally eradicated by current therapies. The classification of breast tumors into distinct molecular subtypes by gene profiling and immunodetection of surrogate markers has proven useful for tumor prognosis and prediction of effective targeted treatments. The challenge now is to identify molecular biomarkers that may be of functional relevance for personalized therapy of breast tumors with poor outcome that do not respond to available treatments. The Mitochondrial Tumor Suppressor (MTUS1) gene is an interesting candidate whose expression is reduced in colon, pancreas, ovary and oral cancers. The present study investigates the expression and functional effects of MTUS1 gene products in breast cancer. METHODS AND FINDINGS: By means of gene array analysis, real-time RT-PCR and immunohistochemistry, we show here that MTUS1/ATIP3 is significantly down-regulated in a series of 151 infiltrating breast cancer carcinomas as compared to normal breast tissue. Low levels of ATIP3 correlate with high grade of the tumor and the occurrence of distant metastasis. ATIP3 levels are also significantly reduced in triple negative (ER- PR- HER2-) breast carcinomas, a subgroup of highly proliferative tumors with poor outcome and no available targeted therapy. Functional studies indicate that silencing ATIP3 expression by siRNA increases breast cancer cell proliferation. Conversely, restoring endogenous levels of ATIP3 expression leads to reduced cancer cell proliferation, clonogenicity, anchorage-independent growth, and reduces the incidence and size of xenografts grown in vivo. We provide evidence that ATIP3 associates with the microtubule cytoskeleton and localizes at the centrosomes, mitotic spindle and intercellular bridge during cell division. Accordingly, live cell imaging indicates that ATIP3 expression alters the progression of cell division by promoting prolonged metaphase, thereby leading to a reduced number of cells ungergoing active mitosis. CONCLUSIONS: Our results identify for the first time ATIP3 as a novel microtubule-associated protein whose expression is significantly reduced in highly proliferative breast carcinomas of poor clinical outcome. ATIP3 re-expression limits tumor cell proliferation in vitro and in vivo, suggesting that this protein may represent a novel useful biomarker and an interesting candidate for future targeted therapies of aggressive breast cancer