Persistent circulating platelet and endothelial derived microparticle signature may explain on-going pro-thrombogenicity after acute coronary syndrome

Aims: Microparticles (MPs) are submicron vesicles, released from activated, and apoptotic cells. MPs are elevated in the circulation of patients with coronary artery disease (CAD) and have pro-thrombotic potential. However, limited data exists on MP signature over time following an acute coronary event. / Methods & results: Circulating total annexin v + (Anv+) MPs of endothelial (EMP), platelet (PMP), monocyte (MMP), neutrophil (NMP) and smooth muscle cell (SMMP) origin were quantified by flow cytometry. 13 patients with acute coronary syndrome (ACS) were prospectively enrolled and 12 patients with stable angina (SA) were included as a comparator group. A panel of MP was measured at baseline, after percutaneous coronary intervention (PCI) and at days 1, 7, 30 and 6 months. Intra & inter group comparison was made between various time points. MP mediated thrombin generation was measured by recording lag phase, velocity index, peak thrombin and endogenous thrombin potential at these time points and compared with healthy controls. The total AnV+ MP levels were similar in ACS and SA groups at baseline, peaked immediately after PCI and were at their lowest on day 1. PMP & EMP levels remained significantly elevated in ACS patients at 6 months when compared to SA. No such difference was noted with NMP, MMP and SMMP. Patients with coronary artery disease showed abnormal thrombograms when compared to controls. Peak thrombin (nano moles) was significantly higher in CAD when compared to controls (254 IQR [226, 239] in ACS, 255 IQR [219, 328] in SA and 132 IQR [57, 252] in controls; p = 0.006). Differences in thrombin generation between ACS and SA were not significant (p = 1). Furthermore, thrombin parameters remained abnormal in ACS & SA patients at 6 months. / Conclusions: Total MP and individual MP phenotypes were significantly elevated after PCI reflecting endothelial injury. Elevated PMP and EMP levels at 6 months in ACS patients is suggestive of on-going inflammation, endothelial injury and may explain on-going pro-thrombogenicity seen up to 6 months after ACS despite dual antiplatelet therapy

Crystallization of a nonreplicating rotavirus vaccine candidate.

Nonreplicating rotavirus vaccine (NRRV) candidates are being developed with the aim of serving the needs of developing countries. A significant proportion of the cost of manufacturing such vaccines is the purification in multiple chromatography steps. Crystallization has the potential to reduce purification costs and provide new product storage modality, improved operational flexibility, and reduced facility footprints. This communication describes a systematic approach for the design of the crystallization of an NRRV candidate, VP8 subunit proteins fused to the P2 epitope of tetanus toxin, using first-principles models and preliminary experimental data. The first-principles models are applied to literature data to obtain feasible crystallization conditions and lower bounds for nucleation and growth rates. Crystallization is then performed in a hanging-drop vapor diffusion system, resulting in the nucleation and growth of NRRV crystals. The crystals obtained in a scaled-up evaporative crystallization contain proteins truncated in the P2 region, but have no significant differences with the original samples in terms of antibody binding and overall conformational stability. These results demonstrate the promise of evaporative crystallization of the NRRV

Holographic aspects of three dimensional QCD from string theory

We study two aspects of 3D QCD with massless fermions in a holographic set-up from string theory, based on D3/D7 branes; parity anomaly and baryons as baby Skyrmions. We first give a novel account of parity anomaly of 3D QCD with odd number of flavors from the IR holographic viewpoint by observing a subtle point in D7 brane embeddings with a given fixed UV theory. We also discuss its UV origin in terms of weakly coupled D-brane pictures. We then focus on the parity-symmetric case of even number of N_F flavors, and study baryons in the holographic model. We identify the monopoles of U(N_F) gauge theory dynamically broken down to U(N_F/2)x U(N_F/2) in the holographic 4 dimensional bulk as a holographic counter-part of 3D baby-Skyrmions for baryons in large N limit, and work out some details how the mapping goes. In particular, we show that the correct baryon charges emerge from the Witten effect with a space-varying theta angle.Comment: 33 pages, 10 figures; v2: references added with comments, typos corrected; v3: more references added; v4: holographic baryon profile and the analysis of its baryon charge is significantly revised, correcting errors in the previous discussio

Pembrolizumab-Induced Pancreatic Exocrine Insufficiency Complicated by Severe Hepatic Steatosis

Anti-programmed death receptor-1 (anti-PD-1) monoclonal antibodies (mAbs) are used to treat an increasing range of cancers. However, the distinct toxicity profile of immune-related adverse events (irAEs) is a frequent drawback of their clinical application. Among the more common irAEs are hepatitis and colitis, which are diagnosed and graded in patients based on elevated serum liver enzyme levels and increased stool frequency, respectively, and both of which often require treatment with high-dose corticosteroids. Herein, we describe the case of a patient who developed severe transaminase elevation and diarrhoea due to an unusual irAE, which was successfully treated without corticosteroids

KK6 from M2 in BLG

We study the possibility that the Kaluza-Klein monopole (KK6) world-volume action may be obtained from the multiple membranes (M2) action which is described by BLG theory. We first point out that the infinite dimensional Lie 3-algebra based on the Nambu-Poisson structure could not only provide three dimensional manifolds to allow M5 from M2, which was studied by previous authors, but also provide five dimensional manifolds to allow KK6 from M2. We next present a possible way that the U(1) field on KK6 world-volume action could be produced form the gauge potential in BLG theory.Comment: Latex, 15 pages. V3: Add theorem 2 to complete proof. V4: Detail physical interpretations and calculations in section

Microparticles and their role in coronary artery disease.

Despite significant advances in prevention, medical and interventional management, coronary artery disease (CAD) remains the leading cause of death worldwide. Although the number of people being diagnosed with CAD has plateaued in the western world, it is projected to increase significantly in the developing world reaching epidemic proportions, particularly in South Asia. To better stratify the risk of developing and suffering a cardiovascular event due to CAD, not only plasma biomarkers relating to disease burden but also disease activity in CAD are needed; this will allow targeting of appropriate management to high-risk patients for acute events. Over the last twenty years, data have emerged showing the role of sub-micron vesicles called microparticles (MPs) in the pathogenesis of formation and evolution of atherosclerotic plaques causing either stable angina (SA) or acute coronary syndromes (ACS). Herein we provide an overview of our current knowledge of MP formation, composition and possible mechanisms through which they could be contributing to CAD. We also reviewed currently available methods and their limitations in quantifying MPs and in determining their functional aspects. Role of various treatments ranging from dietary substitutes to oral medicines and intravenous medications to mechanistic procedures such as hemofiltration are elaborated. Although evidence implicating the role of MPs in CAD are mounting large scale prospective studies are still lacking and are the need of the hour prior to establishing the use of MPs as biomarkers for the early detection of CAD and its progression

A detailed analysis of a multi-agent diverse team

In an open system we can have many different kinds of agents. However, it is a challenge to decide which agents to pick when forming multi-agent teams. In some scenarios, agents coordinate by voting continuously. When forming such teams, should we focus on the diversity of the team or on the strength of each member? Can a team of diverse (and weak) agents outperform a uniform team of strong agents? We propose a new model to address these questions. Our key contributions include: (i) we show that a diverse team can overcome a uniform team and we give the necessary conditions for it to happen; (ii) we present optimal voting rules for a diverse team; (iii) we perform synthetic experiments that demonstrate that both diversity and strength contribute to the performance of a team; (iv) we show experiments that demonstrate the usefulness of our model in one of the most difficult challenges for Artificial Intelligence: Computer Go

Why online medical teams disband? The role of team diversity and leadership type

Purpose: Online medical teams (MTs), involving collaboration between remote healthcare workers, can provide comprehensive and rapid healthcare to patients. The growth in MTs is continuing, with popularity growing among doctors and patients, but some MTs disband, which could break the continuity of healthcare services provided. We aim to address this pressing issue by exploring the effects of team diversity and leadership types on team status (i.e. team disbandment (TD)). This paper systematically investigates the influences of team diversity, including separation, variety and disparity diversity and the effects of leadership types, including strong, equal and weak types. Design/methodology/approach: A data set consisting 1,071 online MTs was collected from the Good Doctor website, a leading Chinese online health community (OHC), on January 10, 2018. The data captured included 206 teams which disbanded after 3 months collaboration. Logistic regression and maximum likelihood estimation (MLE) were used to examine their effects. Findings: The results show that variety diversity, related to departments, positively affects TD, but disparity diversity, referring to clinician titles, negatively affects TD. Separation diversity, in terms of team member attitudes, exerts a negligible influence on disbandment. Although strong and equal leadership types negatively influence TD, they are seen to strengthen the positive effect of variety diversity, suggesting stable structure combinations of strong or equal-type leadership and low department diversity, as well as the match of weak-type leadership and high department diversity. Originality/value: This paper extends the current understanding of virtual teams and OHCs by examining the role of leadership types and team diversity, and their influencing role on team status. The pairwise combinations are obtained to effectively reduce the disbandment probability of medical teams operating in OHCs, which could help platform managers, team founders and those connected with MTs deal with the team-disbandment crisis, providing both theoretical and practical implications to healthcare providers and researchers alike.National Natural Science Foundation Program of China [71671073, 71971092, 71722014, 91646113]