Microbial lysate upregulates host oxytocin

Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. We conclude that microbe viability is not essential for regulating host oxytocin levels. The results suggest that a peptide or metabolite produced by bacteria may modulate host oxytocin secretion for potential public or personalized health goals.Published versio

Stent Thrombogenicity Early in High Risk Interventional Settings is Driven by Stent Design and Deployment, and Protected by Polymer-Drug Coatings

Author Manuscript: 2012 April 5Background—Stent thrombosis is a lethal complication of endovascular intervention. Concern has been raised about the inherent risk associated with specific stent designs and drug-eluting coatings, yet clinical and animal support is equivocal. Methods and Results—We examined whether drug-eluting coatings are inherently thrombogenic and if the response to these materials was determined to a greater degree by stent design and deployment with custom-built stents. Drug/polymer coatings uniformly reduce rather than increase thrombogenicity relative to matched bare metal counterparts (0.65-fold; P=0.011). Thick-strutted (162 μm) stents were 1.5-fold more thrombogenic than otherwise identical thin-strutted (81 μm) devices in ex vivo flow loops (P<0.001), commensurate with 1.6-fold greater thrombus coverage 3 days after implantation in porcine coronary arteries (P=0.004). When bare metal stents were deployed in malapposed or overlapping configurations, thrombogenicity increased compared with apposed, length-matched controls (1.58-fold, P=0.001; and 2.32-fold, P<0.001). The thrombogenicity of polymer-coated stents with thin struts was lowest in all configurations and remained insensitive to incomplete deployment. Computational modeling–based predictions of stent-induced flow derangements correlated with spatial distribution of formed clots. Conclusions—Contrary to popular perception, drug/polymer coatings do not inherently increase acute stent clotting; they reduce thrombosis. However, strut dimensions and positioning relative to the vessel wall are critical factors in modulating stent thrombogenicity. Optimal stent geometries and surfaces, as demonstrated with thin stent struts, help reduce the potential for thrombosis despite complex stent configurations and variability in deployment

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease

The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway

Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway

How to screen for non-adherence to antihypertensive therapy

The quality of assessment of non-adherence to treatment in hypertensive is poor. Within this review, we discuss the different methods used to assess adherence to blood-pressure-lowering medications in hypertension patients. Subjective reports such as physicians’ perceptions are inaccurate, and questionnaires completed by patients tend to overreport adherence and show a low diagnostic specificity. Indirect objective methods such as pharmacy database records can be useful, but they are limited by the robustness of the recorded data. Electronic medication monitoring devices are accurate but usually track adherence to only a single medication and can be expensive. Overall, the fundamental issue with indirect objective measures is that they do not fully confirm ingestion of antihypertensive medications. Detection of antihypertensive medications in body fluids using liquid chromatography–tandem mass spectrometry is currently, in our view, the most robust and clinically useful method to assess non-adherence to blood-pressure-lowering treatment. It is particularly helpful in patients presenting with resistant, refractory or uncontrolled hypertension despite the optimal therapy. We recommend using this diagnostic strategy to detect non-adherence alongside a no-blame approach tailoring support to address the perceptions (e.g. beliefs about the illness and treatment) and practicalities (e.g. capability and resources) influencing motivation and ability to adhere

Primary versus secondary source of data in observational studies and heterogeneity in meta-analyses of drug effects: a survey of major medical journals

The data from individual observational studies included in meta-analyses of drug effects are collected either from ad hoc methods (i.e. "primary data") or databases that were established for non-research purposes (i.e. "secondary data"). The use of secondary sources may be prone to measurement bias and confounding due to over-the-counter and out-of-pocket drug consumption, or non-adherence to treatment. In fact, it has been noted that failing to consider the origin of the data as a potential cause of heterogeneity may change the conclusions of a meta-analysis. We aimed to assess to what extent the origin of data is explored as a source of heterogeneity in meta-analyses of observational studies.publishe

Review of journal of cardiovascular magnetic resonance 2010

There were 75 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2010, which is a 34% increase in the number of articles since 2009. The quality of the submissions continues to increase, and the editors were delighted with the recent announcement of the JCMR Impact Factor of 4.33 which showed a 90% increase since last year. Our acceptance rate is approximately 30%, but has been falling as the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. Last year for the first time, the Editors summarized the papers for the readership into broad areas of interest or theme, which we felt would be useful to practitioners of cardiovascular magnetic resonance (CMR) so that you could review areas of interest from the previous year in a single article in relation to each other and other recent JCMR articles [1]. This experiment proved very popular with a very high rate of downloading, and therefore we intend to continue this review annually. The papers are presented in themes and comparison is drawn with previously published JCMR papers to identify the continuity of thought and publication in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality manuscripts to JCMR for publication

Expedition 376 summary

Volcanic arcs are the surface expression of magmatic systems that result from subduction of mostly oceanic lithosphere at convergent plate boundaries. Arcs with a submarine component include intraoceanic arcs and island arcs that span almost 22,000 km on Earth’s surface, and the vast majority of them are located in the Pacific region. Hydrothermal systems hosted by submarine arc volcanoes commonly contain a large component of magmatic fluid. This magmatic-hydrothermal signature, coupled with the shallow water depths of arc volcanoes and their high volatile contents, strongly influences the chemistry of the fluids and resulting mineralization and likely has important consequences for the biota associated with these systems. The high metal content and very acidic fluids in these hydrothermal systems are thought to be important analogs to numerous porphyry copper and epithermal gold deposits mined today on land. During International Ocean Discovery Program (IODP) Expedition 376 (5 May–5 July 2018), a series of five sites was drilled on Brothers volcano in the Kermadec arc. The expedition was designed to provide the missing link (i.e., the third dimension) in our understanding of hydrothermal activity and mineral deposit formation at submarine arc volcanoes and the relationship between the discharge of magmatic fluids and the deep biosphere. Brothers volcano hosts two active and distinct hydrothermal systems: one is seawater influenced and the other is affected by magmatic fluids (largely gases). In total, 222.4 m of volcaniclastics and lavas were recovered from the five sites drilled, which include Sites U1527 and U1530 in the Northwest (NW) Caldera seawater-influenced hydrothermal field; Sites U1528 and U1531 in the magmatic fluid-influenced hydrothermal fields of the Upper and Lower Cones, respectively; and Site U1529, located within an area of low crustal magnetization that marks the West (W) Caldera upflow zone on the caldera floor. Downhole logging and borehole fluid sampling were completed at two sites, and two tests of a prototype turbine-driven coring system (designed by the Center for Deep Earth Exploration [CDEX] at Japan Agency for Marine-Earth Science and Technology [JAMSTEC]) for drilling and coring hard rocks were conducted. Core recovered from all five sites consists of dacitic volcaniclastics and lava flows with only limited chemical variability relative to the overall range in composition of dacites in the Kermadec arc. Pervasive alteration with complex and variable mineral assemblages attest to a highly dynamic hydrothermal system. The upper parts of several drill holes at the NW Caldera hydrothermal field are characterized by secondary mineral assemblages of goethite + opal + zeolites that result from low-temperature (<150°C) reaction of rock with seawater. At depth, NW Caldera Site U1527 exhibits a higher temperature (~250°C) secondary mineral assemblage dominated by chlorite + quartz + illite + pyrite. An older mineral assemblage dominated by diaspore + quartz + pyrophyllite + rutile at the bottom of Hole U1530A is indicative of acidic fluids with temperatures of ~230°–320°C. In contrast, the alteration assemblage at Site U1528 on the Upper Cone is dominated by illite + natroalunite + pyrophyllite + quartz + opal + pyrite, which attests to high-temperature reaction of rocks with acid-sulfate fluids derived from degassed magmatic volatiles and the disproportionation of magmatic SO2. These intensely altered rocks exhibit extreme depletion of major cation oxides, such as MgO, K2O, CaO, MnO, and Na2O. Furthermore, very acidic (as low as pH 1.8), relatively hot (≤236°C) fluids collected at 160, 279, and 313 meters below seafloor in Hole U1528D have chemical compositions indicative of magmatic gas input. In addition, preliminary fluid inclusion data provide evidence for involvement of two distinct fluids: phase-separated (modified) seawater and a ~360°C hypersaline brine, which alters the volcanic rock and potentially transports metals in the system. The material and data recovered during Expedition 376 provide new stratigraphic, lithologic, and geochemical constraints on the development and evolution of Brothers volcano and its hydrothermal systems. Insights into the consequences of the different types of fluid–rock reactions for the microbiological ecosystem elucidated by drilling at Brothers volcano await shore-based studies