Chemical and behavioural strategies along the spectrum of host specificity in ant-associated silverfish.

BACKGROUND: Host range is a fundamental trait to understand the ecological and evolutionary dynamics of symbionts. Increasing host specificity is expected to be accompanied with specialization in different symbiont traits. We tested this specificity-specialization association in a large group of 16 ant-associated silverfish species by linking their level of host specificity to their degree of behavioural integration into the colony and to their accuracy of chemically imitating the host's recognition system, i.e. the cuticular hydrocarbon (CHC) profile. RESULTS: As expected, facultative associates and host generalists (targeting multiple unrelated ants) tend to avoid the host, whereas host-specialists (typically restricted to Messor ants) were bolder, approached the host and allowed inspection. Generalists and host specialists regularly followed a host worker, unlike the other silverfish. Host aggression was extremely high toward non-ant-associated silverfish and modest to low in ant-associated groups. Surprisingly, the degree of chemical deception was not linked to host specificity as most silverfish, including facultative ant associates, imitated the host's CHC profile. Messor specialists retained the same CHC profile as the host after moulting, in contrast to a host generalist, suggesting an active production of the cues (chemical mimicry). Host generalist and facultative associates flexibly copied the highly different CHC profiles of alternative host species, pointing at passive acquisition (chemical camouflage) of the host's odour. CONCLUSIONS: Overall, we found that behaviour that seems to facilitate the integration in the host colony was more pronounced in host specialist silverfish. Chemical deception, however, was employed by all ant-associated species, irrespective of their degree of host specificity.

Role of fibrinogen concentrates for treatment of critical perioperative hemorrhage.

Acquired hypofibrinogenemia is a frequent cause of maintained bleeding in perioperative high-risk settings. Loss, consumption and dilution under resuscitation fluid therapy are the principal causes for fibrinogen depletion. Severe hypofibrinogenemia is frequently associated with an early bleeding complication that cannot be reliably avoided with high-ratio plasma transfusion strategies. Real-time monitoring with viscoelastic hemostatic assays is a useful tool for timely diagnosis and treatment of detected coagulopathies. Replenishment of fibrinogen in uncontrolled bleeding events is currently recommended by most published guidelines, suggesting treatment thresholds to maintain a minimum of 1.5 g/L plasma fibrinogen concentration for nonobstetrical hemorrhage. Fibrinogen concentrates, originally licensed for treatment of bleeding episodes in patients with congenital hypo-, dys- or afibrinogenemia disorders, are used in many clinical situations as supplementary therapy for the treatment of acquired hypofibrinogenemia. This review seeks to provide an overview of the most relevant topics associated to fibrinogen replacement therapy for critical perioperative hemorrhage highlighting currently available evidence on the risk/benefit profile of purified fibrinogen concentrates for this extended clinical indication.

Diagnostic challenges in von Willebrand disease. Report of two cases with emphasis on multimeric and molecular analysis.

Identification of qualitative variants of von Willebrand disease (VWD) can be a diagnostic challenge because of discrepant results obtained in the multiple laboratory tests available for its appropriate classification. We report two cases of infrequent inherited variants of VWD with unclear preliminary results with the test panel available at the time of first consultation and that were finally diagnosed as a VWD type 2A/IID with a c.8318 G > C, p.Cys2773Ser mutation and a VWD type 2M with c.4225 T > G, p.Val1409Phe mutation, respectively. The description of these two cases highlights that despite the limited diagnostic panel for the evaluation of von Willebrand Factor (VWF) functionality, the multimeric analysis and genetic family studies were fundamental tools to achieve the final diagnosis.

Use of De Novo mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Experience From Clinical Practice.

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.

The Genus Anelpistina (Insecta, Zygentoma, Nicoletiidae) in Puerto Rico, with the Description of a New Species.

Samples of Nicoletiidae (order Zygentoma = Thysanura s. str.) collected in two localities from Puerto Rico belonging to the genus Anelpistina Silvestri, 1905 are studied. One of them, collected in the same cave where A. puertoricensis Espinasa and Baker Alpheis, 2003 was found, allows for the description of the female of this species, together with some additional information on the variability and postembryonic development of this troglobitic insect. The second consists of specimens collected in litter of the islet of Palominos, near the northeastern coast of the main island of Puerto Rico; these specimens are identified as a new species. This species, named Anelpistina naarae sp. nov., is described and compared with related species. A genetic analysis of its DNA and 16S rRNA compared with the available data of the remaining species points to the chronology of the lineages of Anelpistina in this island and their relationships with continental species of the genus.

Effectiveness of Integrative Laughter Therapy to Reduce Anxiety, Improve Self-Esteem and Increase Happiness: A Naturalistic Study at a Day Hospital for Addictive Disorders.

Little is known about the effectiveness of laughter therapy as an adjunctive treatment for patients with addictive disorders. This study aims to evaluate the benefits of integrative laughter therapy (ILT) on levels of self-esteem, anxiety, and happiness in patients treated for addiction at a day hospital (DH). A prospective, naturalistic study with a pre-post design was conducted. All 185 participants received the standard, multicomponent treatment at the DH (treatment as usual; TAU). The participants were also invited to attend weekly ILT sessions. Upon completion of the 2-month DH treatment program, patients were classified according to their attendance at the ILT sessions: patients who attended ≥80% constituted the experimental group (TAU + ILT group) while those who attended <80% were considered controls. Although both groups achieved statistically significant increases in self-esteem and happiness with a decrease in trait anxiety, the improvement on these variables was significantly greater in the TAU + ILT group. Subject to the limitations inherent to quasi-experimental research, the findings of the present study suggest that the addition of an ILT module to the standard treatment in a DH for addictive disorders may yield greater improvement in self-esteem, anxiety, and happiness compared to TAU.

Late Onset Graft Plasmacytoma-Like PTLD Presenting as Acute Hyperglycemia in a Kidney-Pancreas Transplant Recipient.

Allograft infiltration has been described in up to 20% of all patients with posttransplant lymphoproliferative disorder (PTLD), most representing EBV-positive B-cell lymphomas. Plasma cells are often observed in humoral rejection biopsies, but graft infiltration by plasmacytoma-like PTLD is rare. We report the case of a 54-year-old simultaneous pancreas-kidney transplant recipient (immunosuppression: OKT3, methylprednisolone, cyclosporine, and azathioprine), diagnosed with an IgG-kappa monoclonal gammopathy of undetermined significance eighteen years after transplant. Nine months later, pancreas allograft biopsy performed due to new-onset hyperglycemia (HgA1C 8.6%, C-peptide 6.15ng/mL and anti-GAD 0.9UI/mL) revealed a monotypic plasma cell infiltrate, CD19, CD79a, CD138 positive, with IgG-kappa light chain restriction, and EBV negative. PET-scan FDG uptake was limited to pancreas allograft. Tumor origin could not be established (using DNA microsatellite analysis). Despite treatment with bortezomib and dexamethasone, patient eventually died one month later. This is the first report of a late onset extramedullary plasmacytoma involving a pancreas allograft.

(20882) 2000 VH57: AN INNER MAIN-BELT BINARY ASTEROID.

CCD photometric observations of the inner main-belt asteroid (20882) 2000 VH57 were made from 2018 Sept. 15 through Oct. 20. Analysis of the data showed that the asteroid is binary with a primary rotational period of 2.5586 hr and a satellite orbital period of 32.81 hr. Mutual eclipse/occultation events indicate a lower limit on the secondary-to-primary mean diameter ratio (Ds/Dp) of 0.23. During the period of observations, the primary and secondary lightcurves evolved as the viewing aspect changed. In particular, the depth of the secondary event increased significantly towards the end of the observations.

Emicizumab for routine prophylaxis to prevent bleeding episodes in patients with hemophilia A.

Hemophilia A is an X-linked bleeding disorder caused by defects in the gene encoding factor VIII (FVIII). Routine prophylaxis with exogenous FVIII requires frequent intravenous injections. One of the most challenging issues in the treatment of hemophilia A is the development of alloantibodies against infused FVIII. Presence of inhibitors results in an ineffective factor replacement therapy and increases the risk of morbidity and mortality in these patients. Therefore, there is growing interest in the development of new strategies for the prophylaxis and prevention of bleeding in patients with hemophilia to circumvent these drawbacks. Emicizumab (ACE-910; Roche, Genentech and Chugai Pharmaceutical) is a recombinant humanized bispecific antibody that restores the function of missing FVIII by bridging activated FIX and FX, simulating the cofactor function of FVIII.

Betrixaban: a direct oral inhibitor of activated factor X for the prophylaxis of venous thromboembolism in patients hospitalized for acute medical illness.

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a serious clinical and public health concern. Hospitalization is a major risk factor for developing VTE. Hospital-associated events account for more than 50% of all cases of VTE. Heparins have demonstrated to be efficacious in the prevention of VTE in medically ill patients. Despite the demonstrated efficacy and safety of the available direct oral anticoagulants in the prevention and treatment of different thromboembolic conditions, their net benefit in the prevention of VTE in hospitalized medically ill patients has not been fully confirmed. Betrixaban is an oral, specific and direct inhibitor of human coagulation factor Xa with demonstrated efficacy and safety for the prevention of VTE in patients undergoing total knee replacement and in patients with nonvalvular atrial fibrillation. Recent studies have successfully evaluated betrixaban 80 mg once daily in the prevention of VTE in acute medically ill patients in a large phase III trial. This review will address preclinical pharmacology and main aspects of the clinical development of betrixaban as an antithrombotic agent, with specific attention to recent studies on the prophylaxis of VTE in a specific population of patients hospitalized for acute medical illnesses.

Significant and variable linear polarization during the prompt optical flash of GRB 160625B.

Newly formed black holes of stellar mass launch collimated outflows (jets) of ionized matter that approach the speed of light. These outflows power prompt, brief and intense flashes of γ-rays known as γ-ray bursts (GRBs), followed by longer-lived afterglow radiation that is detected across the electromagnetic spectrum. Measuring the polarization of the observed GRB radiation provides a direct probe of the magnetic fields in the collimated jets. Rapid-response polarimetric observations of newly discovered bursts have probed the initial afterglow phase, and show that, minutes after the prompt emission has ended, the degree of linear polarization can be as high as 30 per cent-consistent with the idea that a stable, globally ordered magnetic field permeates the jet at large distances from the central source. By contrast, optical and γ-ray observations during the prompt phase have led to discordant and often controversial results, and no definitive conclusions have been reached regarding the origin of the prompt radiation or the configuration of the magnetic field. Here we report the detection of substantial (8.3 ± 0.8 per cent from our most conservative simulation), variable linear polarization of a prompt optical flash that accompanied the extremely energetic and long-lived prompt γ-ray emission from GRB 160625B. Our measurements probe the structure of the magnetic field at an early stage of the jet, closer to its central black hole, and show that the prompt phase is produced via fast-cooling synchrotron radiation in a large-scale magnetic field that is advected from the black hole and distorted by dissipation processes within the jet.

Endothelial damage is aggravated in acute GvHD and could predict its development.

The aim of the present study was to explore whether there is enhanced endothelial dysfunction in patients developing acute GvHD (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) and to identify biomarkers with predictive and/or diagnostic value. In in vitro experiments, endothelial cells (ECs) were exposed to serum from patients with (aGvHD, n=31) and without (NoGvHD, n=13) aGvHD, to evaluate changes in surface adhesion receptors, the reactivity of the extracellular matrix by measuring the presence of Von Willebrand factor (VWF) and platelet adhesion, and the activation of intracellular signaling proteins. Plasma levels of VWF, ADAMTS-13, TNF receptor 1 (TNFR1), soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1 were also measured. In vitro results showed a more marked proinflammatory and prothrombotic phenotype in ECs in association with aGvHD. Regarding circulating biomarkers, levels of VWF and TNFR1 above an optimal cutoff score, taken independently or combined, at day 7 after allo-HCT, would be able to positively predict that around 90% of patients will develop aGvHD. Our results demonstrate that endothelial damage is aggravated in those allo-HCT recipients developing aGvHD, and that VWF and TNFR1 are promising predictive aGvHD biomarkers. These findings could contribute to improve the understanding of the pathophysiology of aGvHD.

Andexanet alfa: a recombinant mimetic of human factor Xa for the reversal of anticoagulant therapies.

Activated coagulation factor X (FXa) is a common target for classic and newer anticoagulants. Parenteral anticoagulants with an indirect inhibitory action on FXa (low-molecular-weight heparins) have a well-established clinical efficacy in the prophylaxis and therapy of thromboembolic conditions. More recently developed direct oral anticoagulants (DOACs) have emerged as a new class of antithrombotic drugs. Rivaroxaban, apixaban and edoxaban are direct inhibitors of FXa approved for the management of venous thromboembolism and stroke prevention in atrial fibrillation. Although these DOACs are associated with fewer hemorrhagic side effects than classic vitamin K antagonists, bleeding is still a main complication. FXa antagonists had no specific agents that could reverse their antihemostatic effects. Andexanet alfa is a modified, recombinant human FXa molecule with an enhanced ability to bind to both direct and indirect FXa inhibitors, but unable to contribute to blood coagulation mechanisms. Andexanet alfa is designed to reverse the anticoagulant effects of FXa inhibitors. This review will address the preclinical pharmacology and the main aspects of the clinical development of andexanet alfa for the reversal of anticoagulant therapies with an inhibitory action on FXa. It will also summarize additional completed or ongoing studies on andexanet alfa available to the scientific community until present.

Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.

OBJECTIVE: Defective trophoblastic invasion is a key feature in many cases of pre-eclampsia (PE). Uterine artery (UtA) Doppler is a validated non-invasive proxy for trophoblastic invasion. The aim of this study was to explore whether low-dose aspirin, administered from the first trimester, improves trophoblastic invasion, evaluated by UtA Doppler during the second and third trimesters in women defined as high risk by abnormal first-trimester UtA Doppler. METHODS: This randomized Phase-II study had a triple-blind, parallel-arm, controlled design. Singleton pregnancies with abnormal mean UtA Doppler at 11-14 weeks and absence of other major risk factors for PE received 150 mg extended-release aspirin or identical-appearing placebo tablets from study inclusion to 28 weeks. Main outcome measure was UtA pulsatility index (PI) at 28 weeks' gestation. Secondary outcomes included frequency of development of PE and growth restriction/small-for-gestational age (SGA). RESULTS: A total of 155 women completed the follow-up and were analyzed. No difference in mean UtA-PI was found between women in the aspirin and placebo groups at 28 weeks (mean UtA-PI Z-score (mean ± SD), 0.99 ± 1.48 vs 0.85 ± 1.25; P = 0.52). Seven women developed PE: four (5%) in the aspirin group and three (4%) in the placebo group. There was a trend toward lower incidence of SGA in the aspirin group (8.8% vs 17.3%; P = 0.11). CONCLUSION: In women with defective trophoblastic invasion, as reflected by abnormal UtA Doppler, low-dose aspirin started in the first trimester does not have a significant effect on UtA impedance as pregnancy progresses; however, the study was underpowered to detect potential small effects . Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.

There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (P<0.01 versus CON) and gradually decreased during treatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (P<0.05 versus CON). These results were normalized in cells exposed to MD-24 sera. Thrombogenicity of extracellular matrices generated by these cells, measured as expression of VWF, tissue factor and platelet reactivity, showed non-significant differences. We provide a model of cultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks.

Desensitization in ABO-Incompatible Kidney Transplantation With Low ABO Iso-Agglutinin Titers.

BACKGROUND: In ABO-incompatible (ABOi) kidney transplantation (KT) with low iso-agglutinin (IG) titers (IGT), standard pre-conditioning treatment might be excessive. To try to answer this question, we evaluated the pre-conditioning requirements of a group of ABOi KT with low ABO IGT in our center. Our main objective was to assess desensitization requirements for ABOi KT with low IGT (<16) at Hospital Clinic of Barcelona from 2006 to 2014. METHODS: A retrospective study of desensitization (rituximab and plasma exchange [PE]) requirements for ABOi KT with IGT <16 was conducted. RESULTS: One and 5 years after KT, patient survival was 100%. Renal graft survival was 90% at 1 and 5 years after KT. Mean PE performed before KT was 1.7 (standard deviation [SD], 1.703); 50% of the patients did not receive PE after transplantation, 30% received 2 sessions of PE, and 20% received only 1. The average is 0.8 (SD, 0.91).Follow-up IG determinations remained with low titers (≤8/8). No rebounds of titers were observed during the first 4 to 6 months after transplantation. CONCLUSIONS: Recipients with IGT ≤8 required none or only 1 PE session to reach acceptable titers (titers ≤4) to perform ABOi KT safely. This information is useful to assess the possibility of a minimized desensitization protocol in ABOi KT donors with low titers of IG to reduce adverse effects, reduce cost, and simplify pre-transplant logistics.

Pre-Emptive Retransplantation in Patients With Chronic Kidney Graft Failure.

INTRODUCTION: The aim of this study was to compare the group of patients receiving a new kidney transplant before starting dialysis again (pre-reTR) with a group of patients receiving a new kidney transplant after restarting dialysis (reTR). METHODS: This retrospective cohort included all the kidney retransplantations (second transplantations) between 2000 and 2012 performed at our center and their follow-up until July 2014. We analysed graft and patient survival, rejection rates, and immunologic parameters of these patients. RESULTS: We studied 18 patients who had pre-reTR and 83 who had reTR. In the pre-reTR group no patient had panel-reactive assay (PRA) >10% at any time. In the reTR group 26.5% had PRA >10% at the time of transplantation (P = .014) and 54.2% had a historical highest PRA >10% (P < .001). The rejection rate was 11.1% in the pre-reTR group and 27.7% in the reTR group during the first year post-retransplantation (P = .227). Patient survival rate was 100% in the pre-reTR group at 5 years of follow-up, whereas in the reTR group at 1 year it was 95.2% and 85.9% at 5 years after retransplantation. Allograft survival at 1 and 5 years was 88% and 89%, respectively, in the pre-reTR group. On the other hand, in the reTR group it was 89% after the first year and 65% at 5 years post-retransplantation. CONCLUSION: Pre-emptive renal retransplantation is a feasible option that should be assessed in patients with kidney graft failure and may help to minimize the morbidity associated with dialysis reinitiation.