bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukocyte-Expressed β
2
-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury
Authors: Grisanti Laurel A. , Gumpert Anna M. , Traynham Christopher J. , Gorsky Joshua E. , Repas Ashley A. , Gao Erhe , Carter Rhonda L. , Yu Daohai , Calvert John W. , García Andrés Pun , Ibáñez Borja , Rabinowitz Joseph E. , Koch Walter J. , Tilley Douglas G. 
Published: July 2016

Background:
Immune cell–mediated inflammation is an essential process for mounting a repair response after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune system function through β-adrenergic receptors (βARs); however, their role in regulating immune cell responses to acute cardiac injury is unknown.

Methods:
Wild-type (WT) mice were irradiated followed by isoform-specific βAR knockout (βARKO) or WT bone-marrow transplantation (BMT) and after full reconstitution underwent MI surgery. Survival was monitored over time, and alterations in immune cell infiltration after MI were examined through immunohistochemistry. Alterations in splenic function were identified through the investigation of altered adhesion receptor expression.

Results:

β
2
ARKO BMT mice displayed 100% mortality resulting from cardiac rupture within 12 days after MI compared with ≈20% mortality in WT BMT mice. β
2
ARKO BMT mice displayed severely reduced post-MI cardiac infiltration of leukocytes with reciprocally enhanced splenic retention of the same immune cell populations. Splenic retention of the leukocytes was associated with an increase in vascular cell adhesion molecule-1 expression, which itself was regulated via β-arrestin–dependent β
2
AR signaling. Furthermore, vascular cell adhesion molecule-1 expression in both mouse and human macrophages was sensitive to β
2
AR activity, and spleens from human tissue donors treated with β-blocker showed enhanced vascular cell adhesion molecule-1 expression. The impairments in splenic retention and cardiac infiltration of leukocytes after MI were restored to WT levels via lentiviral-mediated re-expression of β
2
AR in β
2
ARKO bone marrow before transplantation, which also resulted in post-MI survival rates comparable to those in WT BMT mice.

Conclusions:

Immune cell–expressed β
2
AR plays an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration.
Transglutaminase is a Critical Link Between Inflammation and Hypertension
Authors: Luo Renna , Liu Chen , Elliott Serra E. , Wang Wei , Parchim Nicholas , Iriyama Takayuki , Daugherty Patrick S. , Tao Lijian , Eltzschig Holger K. , Blackwell Sean C. , Sibai Baha M. , Kellems Rodney E. , Xia Yang 
Published: July 2016

Background

The pathogenesis of essential hypertension is multifactorial with different underlying mechanisms contributing to disease. We have recently shown that
TNF
superfamily member 14
LIGHT
(an acronym for homologous to lymphotoxins, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, also known as
TNFSF
14) induces hypertension when injected into mice. Research reported here was undertaken to examine the role of transglutaminase (
TG
ase) in
LIGHT
‐induced hypertension.

Methods and Results

Initial experiments showed that plasma and kidney
TG
ase activity was induced by
LIGHT
infusion (13.91±2.92 versus 6.75±1.92 mU/mL and 19.86±3.55 versus 12.00±0.97 mU/10 μg) and was accompanied with hypertension (169±7.16 versus 117.17±11.57 mm Hg at day 14) and renal impairment (proteinuria, 61.33±23.21 versus 20.38±9.01 μg/mg; osmolality, 879.57±93.02 versus 1407.2±308.04 mmol/kg). The increase in renal
TG
ase activity corresponded to an increase in
RNA
for the tissue TGase isoform, termed
TG
2. Pharmacologically, we showed that
LIGHT
‐induced hypertension and renal impairment did not occur in the presence of cystamine, a well‐known competitive inhibitor of
TG
ase activity. Genetically, we showed that
LIGHT
‐mediated induction of
TG
ase, along with hypertension and renal impairment, was dependent on interleukin‐6 and endothelial hypoxia inducible factor‐1α. We also demonstrated that interleukin‐6, endothelial hypoxia inducible factor‐1α, and
TG
ase are required for
LIGHT
‐induced production of angiotensin receptor agonistic autoantibodies.

Conclusions

Thus,
LIGHT
‐induced hypertension, renal impairment, and production of angiotensin receptor agonistic autoantibodies require
TG
ase, most likely the
TG
2 isoform. Our findings establish
TG
ase as a critical link between inflammation, hypertension, and autoimmunity.
How Patient Demographics, Imaging, and Beliefs Influence Tissue-Type Plasminogen Activator Use
Authors: Shamy Michel C.F. , Pugliese Michael , Meisel Karl , Rodriguez Rosendo , Kim Anthony S. , Stahnisch Frank W. , Smith Eric E. 
Published: July 2016

Background and Purpose—
Understanding physician decision making is increasingly recognized as an important topic of study, especially in stroke care. We sought to characterize the process of acute stroke decision making among neurologists in the United States and Canada from clinical and epistemological perspectives.

Methods—
Using a factorial design online survey, respondents were presented with clinical data to mimic an acute stroke encounter. The history, examination, computed tomographic (CT) scan, CT angiogram, and CT perfusion were presented in sequence, and respondents rated their diagnostic confidence and likelihood of treatment with tissue-type plasminogen activator after each element. Patient age, race, sex, and CT perfusion imaging results were randomized, whereas the rest of the clinical presentation was held constant.

Results—
We collected 715 responses, of which 473 (66%) were complete. Diagnostic certainty and likelihood of treatment with tissue-type plasminogen activator rose incrementally as additional clinical data were provided. Diagnostic certainty and treatment likelihood were strongly influenced by the clinical history and the CT scan. Other factors such as physicians’ personal beliefs or biases were not influential. Respondents’ accuracy in interpreting CT angiographic and CT perfusion images was variable and generally low.

Conclusions—
Diagnostic certainty and likelihood of treatment with tissue-type plasminogen activator increase with additional clinical data, with the history being the most important factor for diagnostic and treatment decisions. Respondents had difficulty in interpreting the results of CT perfusion scans although they had little impact on treatment decisions. We did not identify treatment bias based on patient age, race, or sex.
Application of Satellite- and NWP-Derived Wind Profiles to Military Airdrop Operations
Authors: Meier David C. , Fiorino Steven T. 
Published: July 2016

AbstractThe Joint Precision Airdrop System (JPADS) has revolutionized military high-altitude airdrop capability, allowing delivery of equipment and supplies to smaller drop zones from higher altitudes than was previously possible. This capability relies on accurate wind data, currently provided by GPS dropsondes released in the vicinity of the drop zone shortly before the airdrop. This research investigates the potential for a wind-profiling algorithm to generate the required wind data from passive IR and microwave satellite soundings, eliminating the requirement for a hazardous dropsonde pass near the drop zone. The Atmospheric Infrared Sounder (AIRS) provides a 3D temperature field and determines the heights of 100 standard levels. From these data, the slopes of the isobaric pressure surfaces and temperature gradients are used to calculate wind speed and direction using the thermal wind relationship. The accuracy of these satellite-derived wind profiles is evaluated through comparison with rawinsonde measurements near the coordinates and time of the AIRS sounding. Further investigation of the wind profile accuracy is made by a comparison with numerical weather prediction (NWP) data worldwide, and the effect of cloud cover in the vicinity of the target coordinates is analyzed. The AIRS-derived winds are found to be less accurate than short-term NWP winds for the JPADS application, but the technique developed may be applied to alternate applications, such as use in the stratosphere, where NWP winds are not widely available. The agreement between satellite-retrieved temperatures and measurements at altitudes above 30 km indicates the AIRS data could be used to create accurate, 3D fields of optical turbulence strengths for directed-energy applications.
Usability and feasibility of a mobile health system to provide comprehensive antenatal care in low-income countries: PANDA mHealth pilot study in Madagascar
Authors: Benski Anne Caroline , Stancanelli Giovanna , Scaringella Stefano , Herinainasolo Josea Léa , Jinoro Jéromine , Vassilakos Pierre , Petignat Patrick , Schmidt Nicole C 
Published: July 2016

Background Madagascar’s maternal health mortality ratio in 2013 was 478 deaths per 100,000 live births. Most deaths are related to direct complications during pregnancy and childbirth and could be reduced by providing comprehensive antenatal care (ANC). Objective The objective of the study was to assess the usability and feasibility of a mobile health system (mHealth) to provide high-quality ANC, according to World Health Organization (WHO) recommendations. Methods PANDA (Pregnancy And Newborn Diagnostic Assessment) is an easy-to-use mHealth system that uses affordable communications technology to support diagnosis and health care worker decision-making regarding ANC. From January to March 2015, a cross-sectional pilot study was conducted in Ambanja District, Madagascar, in which ANC using PANDA was provided to 100 pregnant women. The collected data were transmitted to a database in the referral hospital to create individual electronic patient records. Accuracy and completeness of the data were closely controlled. The PANDA software was assessed and the number of abnormal results, treatments performed, and participants requiring referral to health care facilities were monitored. Results The PANDA system facilitated creation of individual electronic patient records that included socio-demographic and medical data for 100 participants. Duration of ANC visits averaged 29.6 min. Health care providers were able to collect all variables (100%) describing personal and medical data. No major technical problems were encountered and no data were lost. During 17 ANC visits (17%), an alert function was generated to highlight abnormal clinical results requiring therapy or referral to an affiliated hospital. Participants’ acceptability of the system was very high. Conclusion This pilot study proved the usability and feasibility of the PANDA mHealth system to conduct complete and standardised ANC visits according to WHO guidelines, thus providing a promising solution to increase access to high-quality and standardised ANC for pregnant women in remote areas.
Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell–derived lymphomas
Authors: Vallois David , Dobay Maria Pamela D. , Morin Ryan D. , Lemonnier François , Missiaglia Edoardo , Juilland Mélanie , Iwaszkiewicz Justyna , Fataccioli Virginie , Bisig Bettina , Roberti Annalisa , Grewal Jasleen , Bruneau Julie , Fabiani Bettina , Martin Antoine , Bonnet Christophe , Michielin Olivier , Jais Jean-Philippe , Figeac Martin , Bernard Olivier A. , Delorenzi Mauro , Haioun Corinne , Tournilhac Olivier , Thome Margot , Gascoyne Randy D. , Gaulard Philippe , de Leval Laurence 
Published: July 2016

Key Points
A high frequency of diverse activating mutations in costimulatory/TCR-related signaling genes occurs in AITL and other TFH-derived PTCL. Deregulated TCR activation may play a role in the pathogenesis of TFH-derived PTCL, paving the way for developing novel targeted therapies.
FcγR mediates TLR2- and Syk-dependent NLRP3 inflammasome activation by inactivated Francisella tularensis LVS immune complexes
Authors: Duffy Ellen B , Periasamy Sivakumar , Hunt Danielle , Drake James R , Harton Jonathan A 
Published: July 2016

Abstract
IgG (mAb)-opsonized, inactivated Francisella tularensis LVS (iFt-mAb) enhances TLR2-dependent IL-6 production by macrophages via Fcγ receptors (FcγR). In mice, vaccination with iFt-mAb provides IgA-dependent protection against lethal challenge with Ft LVS. Because inflammasome maturation of IL-1β is thought important for antibody-mediated immunity, we considered the possibility that iFt-mAb elicits an FcγR-dependent myeloid cell inflammasome response. Herein, we find that iFt-mAb enhances macrophage and dendritic cell IL-1β responses in a TLR2- and FcγR-dependent fashion. Although iFt-mAb complexes bind FcγR and are internalized, sensing of cytosolic DNA by absent in melanoma 2 (AIM2) is not required for the IL-1β response. In contrast, ASC, caspase-1, and NLR family pyrin domain-containing 3 (NLRP3) are indispensable. Further, FcγR-mediated spleen tyrosine kinase (Syk) signaling is required for this NLRP3-dependent IL-1β response, but the alternative IL-1β convertase caspase-8 is insufficient. Finally, iFt-mAb-vaccinated wild-type mice exhibit a significant delay in time to death, but IL-1R1– or Nlrp3-deficient mice vaccinated in this way are not protected and lack appreciable Francisella-specific antibodies. This study demonstrates that FcγR-mediated Syk activation leads to NLRP3 inflammasome-dependent IL-1β production in macrophages and suggests that an Nlrp3- and IL-1R–dependent process contributes to the IgA response important for protection against Ft LVS. These findings extend our understanding of cellular responses to inactivated pathogen-opsonized vaccine, establish FcγR-elicited Syk kinase-mediated NLRP3 inflammasome activation, and provide additional insight toward understanding crosstalk between TLR and FcγR signals.
A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs
Authors: Scales Brittan S , Dickson Robert P , Huffnagle Gary B 
Published: July 2016

Abstract
Inflammation can directly and indirectly modulate the bacterial composition of the microbiome. Although studies of inflammation primarily focus on its function to negatively select against potential pathogens, some bacterial species have the ability to exploit inflammatory byproducts for their benefit. Inflammatory cells release reactive nitrogen species as antimicrobial effectors against infection, but some facultative anaerobes can also utilize the increase in extracellular nitrate in their environment for anaerobic respiration and growth. This phenomenon has been studied in the gastrointestinal tract, where blooms of facultative anaerobic Gammaproteobacteria, primarily Escherichia coli, often occur during colonic inflammation. In cystic fibrosis, Pseudomonas aeruginosa, another Gammaproteobacteria facultative anaerobe, can reduce nitrogen for anaerobic respiration and it blooms in the airways of the chronically inflamed cystic fibrosis lung. This review focuses on the evidence that inflammation can provide terminal electron acceptors for anaerobic respiration and can support blooms of facultative anaerobes, such as E. coli and P. aeruginosa in distinct, but similar, environments of the inflamed gastrointestinal and respiratory tracts.
A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8
Authors: Kamoshida Go , Tansho-Nagakawa Shigeru , Kikuchi-Ueda Takane , Nakano Ryuichi , Hikosaka Kenji , Nishida Satoshi , Ubagai Tsuneyuki , Higashi Shouichi , Ono Yasuo 
Published: July 2016

Abstract
Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target.
Plastic restriction of HIV-1 replication in human macrophages derived from M1/M2 polarized monocytes
Authors: Graziano Francesca , Vicenzi Elisa , Poli Guido 
Published: July 2016

Abstract
M1/M2 cytokine-dependent polarization of primary human MDMs has been shown to contain CCR5-dependent (R5) HIV-1 replication. In this study, a similar effect was achieved when monocytes were first polarized toward M1 or M2 and were infected 7 d after their differentiation into MDMs, regardless of whether the cytokines were removed 18 h after cell stimulation or were left in culture. Unlike polarized MDMs, no significant down-regulation of CD4 from the cell surface was observed in MDMs derived from M1/M2-polarized monocytes. A second stimulation of MDMs differentiated from M1/M2 monocytes with the opposite polarizing cytokines converted the virus replication profile according to the new stimuli. The expression of M1 and M2 markers (i.e., APOBEC3A and DC-SIGN, respectively) was induced by MDM stimulation with the opposite cytokines, although it also persisted in cells according to their first stimulatory condition. Thus, stimulation of monocytes with M1- and M2-inducing cytokines leads to a restriction of HIV-1 replication when these cells are infected several days later as differentiated MDMs. These observations imply that activation of circulating monocytes significantly influences their capacity to either support or restrict HIV-1 replication, once extravasated, and eventually to become infected as tissue macrophages.
Lessons from a double-transgenic neutrophil approach to induce antiproteinase 3 antibody–mediated vasculitis in mice
Authors: Schreiber Adrian , Eulenberg-Gustavus Claudia , Bergmann Astrid , Jerke Uwe , Kettritz Ralph 
Published: July 2016

Abstract
ANCA to either PR3 or MPO are found in patients with necrotizing vasculitis and glomerulonephritis. ANCA binding to their target antigens on neutrophils and subsequent neutrophil activation are pivotal disease mechanisms that lead to vascular inflammation and necrosis. ANCA interaction with PR3 is more complex than with MPO as the neutrophil-specific CD177 receptor is involved in PR3 surface expression and PR3-ANCA–induced neutrophil activation. Modeling human disease is important to clinical research. Highly successful mouse models of MPO-ANCA vasculitis exist; however, recapitulating PR3-ANCA vasculitis has not been successful. We generated double-transgenic (DT) mice that expressed human PR3 and CD177 under a myeloid-specific huMRP8 promoter in an attempt to model PR3-ANCA vasculitis. DT mice strongly expressed the human transgenes in and on murine neutrophils and bound murine and human anti-PR3 antibodies. Nevertheless, passive transfer of these antibodies into LPS-primed DT mice or immunization of C57BL/6 mice with human PR3 followed by irradiation and transplantation of DT bone marrow failed to induce glomerulonephritis. Further analyses revealed that anti-PR3 antibodies did not activate DT neutrophils as shown by superoxide generation. Moreover, we found that mice did not properly process human pro-PR3 into mature PR3 and, consequently, the signaling complex between PR3, CD177, and CD11b, which promotes neutrophil activation by anti-PR3 antibodies, failed to form. We conclude that important species differences in PR3 and CD177 exist between men and mice that prevented successful generation of a murine anti-PR3 antibody model.
The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function
Authors: Conroy Melissa J , Fitzgerald Vivienne , Doyle Suzanne L , Channon Shauna , Useckaite Zivile , Gilmartin Niamh , O’Farrelly Cliona , Ravi Narayanasamy , Reynolds John V , Lysaght Joanne 
Published: July 2016

Abstract
The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α+ and NKP46+ NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role.
Psychiatric expert evidence and the new partial defences of diminished responsibility and loss of control
Authors: Nathan Rajan , Medland Simon 
Published: July 2016

SummaryPsychiatric expert witnesses instructed to undertake assessments of defendants charged with murder should be familiar with the partial defences of diminished responsibility and loss of control. The Coroners and Justice Act 2009 enacted major amendments to the partial defence of diminished responsibility and introduced a new defence of loss of control to replace the provocation partial defence. In this article, the changes to the law are described with particular focus on the implications for the psychiatric assessment.
The value of psychiatrists in leadership and management
Authors: Perry Jennifer , Mason Fiona L. 
Published: July 2016

SummaryThe health and social care landscape in the UK is changing, and there is now, more than ever, a real need for doctors to embrace leadership and management. Evidence shows that medical leadership is associated with better outcomes for patients. Psychiatrists are particularly well suited to such roles, given the interpersonal skills and self-awareness that they develop in their training. In this article, we examine the role of the psychiatrist in leading at a patient, team and organisational level and the impact this has. We also discuss different leadership and management styles.