bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflation Dynamics in a Small Open Economy
Authors: Boug Pål , Cappelen Ådne , Swensen Anders Rygh 
Published: June 2016

AbstractWe evaluate the empirical performance of forward‐looking models for inflation dynamics in a small open economy. Using likelihood‐based testing procedures, we find that the exact formulation is at odds with Norwegian data. Moreover, some of the parameters in the model are not well identified. We also find that the inexact formulation is not rejected statistically using a test based on a minimum distance method. However, confidence regions also reveal an identification problem with this model. Instead, we find a well‐specified backward‐looking model with imperfect competition underlying the price setting, which is a model that outperforms an alternative forward‐looking model in‐sample. The backward‐looking model also forecasts somewhat better than the alternative forward‐looking model, during and after the recent financial crisis.
Adherence clubs for long‐term provision of antiretroviral therapy: cost‐effectiveness and access analysis from Khayelitsha, South Africa
Authors: Bango Funeka , Ashmore John , Wilkinson Lynne , van Cutsem Gilles , Cleary Susan 
Published: June 2016

AbstractObjectivesAs the scale of the South African HIV epidemic calls for innovative models of care that improve accessibility for patients while overcoming chronic human resource shortages, we (i) assess the cost‐effectiveness of lay health worker‐led group adherence clubs, in comparison with a nurse‐driven ‘standard of care’ and (ii) describe and evaluate the associated patient cost and accessibility differences.MethodsOur cost‐effectiveness analysis compares an ‘adherence club’ innovation to conventional nurse‐driven care within a busy primary healthcare setting in Khayelitsha, South Africa. In each alternative, we calculate provider costs and estimate rates of retention in care and viral suppression as key measures of programme effectiveness. All results are presented on an annual or per patient‐year basis. In the same setting, a smaller sample of patients was interviewed to understand the direct and indirect non‐healthcare cost and access implications of the alternatives. Access was measured using McIntyre and colleagues’ 2009 framework.ResultsAdherence clubs were the more cost‐effective model of care, with a cost per patient‐year of $300 vs. $374 and retention in care at 1 year of 98.03% (95% CI 97.67–98.33) for clubs vs. 95.49% (95% CI 95.01–95.94) for standard of care. Viral suppression in clubs was 99.06% (95% CI 98.82–99.27) for clubs vs. 97.20% (95% CI 96.81–97.56) for standard of care. When interviewed, club patients reported fewer missed visits, shorter waiting times and higher acceptability of services compared to standard of care.ConclusionsAdherence clubs offer the potential to enhance healthcare efficiency and patient accessibility. Their scale‐up should be supported.
The systemic nodule number regulation kinase SUNN in Medicago truncatula interacts with MtCLV2 and MtCRN
Authors: Crook Ashley D. , Schnabel Elise L. , Frugoli Julia A. 
Published: June 2016

SummaryAutoregulation of nodulation (AON), a systemic signaling pathway in legumes, limits the number of nodules formed by the legume in its symbiosis with rhizobia. Recent research suggests a model for the systemic regulation in Medicago truncatula in which root signaling peptides are translocated to the shoot where they bind to a shoot receptor complex containing the leucine‐rich repeat receptor‐like kinase SUNN, triggering signal transduction which terminates nodule formation in roots. Here we show that a tagged SUNN protein capable of rescuing the sunn‐4 phenotype is localized to the plasma membrane and is associated with the plasmodesmata. Using bimolecular fluorescence complementation analysis we show that, like its sequence ortholog Arabidopsis CLV1, SUNN interacts with homologous CLV1‐interacting proteins MtCLAVATA2 and MtCORYNE. All three proteins were also able to form homomers and MtCRN and MtCLV2 also interact with each other. A crn Tnt1 insertion mutant of M. truncatula displayed a shoot controlled increased nodulation phenotype, similar to the clv2 mutants of pea and Lotus japonicus. Together these data suggest that legume AON signaling could occur through a multi‐protein complex and that both MtCRN and MtCLV2 may play roles in AON together with SUNN.
Bone‐marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution‐quantitative computed tomography
Authors: Peña Jaime A. , Thomsen Felix , Damm Timo , Campbell Graeme M. , Bastgen Jan , Barkmann Reinhard , Glüer Claus C. 
Published: June 2016

Purpose:Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat‐induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow‐fat density in the axial skeleton.Methods:The authors developed and tested two high resolution‐QCT (HR‐QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone‐void space. To determine their performance, data were compared ex vivo to high‐resolution peripheral CT (HR‐pQCT) images as the gold‐standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD.Results:86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR‐pQCT images were correctly identified on HR‐QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm3 corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods.Conclusions:The GTP and MF methods on HR‐QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.
Eccentric Exercises Reduce Hamstring Strains in Elite Adult Male Soccer Players: A Critically Appraised Topic
Authors: Shadle Ian B. , Cacolice Paul A. 
Published: June 2016

Clinical Scenario:Hamstring strains are a common sport-related injury, which may limit athletic performance for an extended period of time. These injuries are common in the soccer setting. As such, it is important to determine an appropriate prevention program to minimize the risk of such an injury for these athletes. Eccentric hamstring training may be an effective and practical hamstring strain prevention strategy.Clinical Question:What is the effect of eccentric exercises on hamstring strain prevention in adult male soccer players?Summary of Key Findings:Current literature was searched for studies of level 2 evidence or higher that investigated the effect of eccentric exercises in preventing hamstring strains in adult male soccer players. Three articles returned from the literature search met the inclusion criteria. A fourth article looked at differences in strength gains between eccentric and concentric hamstring strengthening exercises, but did not record hamstring strain incidence. A fifth article, a systematic review, met all the criteria except for the correct population. Of the 3 studies, 2 were randomized control trails and 1 was a cohort study.Clinical Bottom Line:There is robust supportive evidence that eccentric hamstring exercises can prevent a hamstring injury to an elite adult male soccer player. Therefore, it is recommended that athletic trainers and other sports medicine providers evaluate current practices relating to reducing hamstring strains and consider implementing eccentric exercise based prevention programs.Strength of Recommendation:All evidence was attained from articles with a level of evidence 2b or higher, based on the Center for Evidence-Based Medicine (CEBM) criteria, stating that eccentric exercises can decrease hamstring strains.
Effects of a 6-Week Neuromuscular Rehabilitation Program on Ankle-Evertor Strength and Postural Stability in Elite Women Field Hockey Players With Chronic Ankle Instability
Authors: Kim Taegyu , Kim Eunkuk , Choi Hokyung 
Published: June 2016

Objective:To determine whether a neuromuscular rehabilitation program can improve postural stability and ankle-evertor strength and to examine the temporal changes and persistence of the rehabilitation effects in athletes with chronic ankle instability (CAI).Design:A total of 21 national women field hockey players participated in this study (CAI, n = 12; control, n = 9).Main Outcome Measures:Isokinetic ankle-evertor strength (peak torque [PT], total work [TW]) at 30°/s, 60°/s, 90°/s, and 120°/s, mediolateral stability index (MSI), and dynamic stability test (TCT). Data were recorded at baseline, 6 wk, and 24 wk.Results:At baseline, isokinetic evertor strength was comparable between groups. At 6 wk, the CAI group demonstrated significantly increased eccentric PT and TW at 30°/s and 60°/s and increased concentric/eccentric TW at 90°/s. The control group showed significantly increased concentric TW at 30°/s and increased concentric PT and TW at 90°/s. At 24 wk, except for eccentric PT at 60°/s and 120°/s, concentric/eccentric PT and TW were significantly increased in the CAI group. The control group showed significantly increased TW at all angular velocities regardless of contraction mode. The CAI group exhibited significant increases in concentric/eccentric evertor PT and TW at 120°/s in comparison with the control group. MSI and TCT decreased in both groups at 6 wk; however, the CAI group demonstrated significant increases in both measures at 24 wk, whereas the control group showed no significant change.Conclusions:The results suggest that the neuromuscular rehabilitation program had an immediate effect on gaining eccentric evertor strength and improving postural control and appeared to contribute to enhancing the evertor strength of unstable ankles in the longer term. On the other hand, improved postural stability did not seem to persist.
In Vitro
Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections
Authors: Reitzel Ruth A. , Rosenblatt Joel , Hirsh-Ginsberg Cheryl , Murray Kimberly , Chaftari Anne-Marie , Hachem Ray , Raad Issam 
Published: June 2016

ABSTRACT

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant
Staphylococcus aureus
(MRSA), vancomycin-intermediate
Staphylococcus aureus
(VISA), methicillin-resistant
Staphylococcus epidermidis
(MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR)
Pseudomonas aeruginosa
, MDR
Klebsiella pneumoniae
, MDR
Enterobacter cloacae
, MDR
Acinetobacter baumannii
, MDR
Escherichia coli
, MDR
Stenotrophomonas maltophilia
,
Candida albicans
, and
Candida glabrata
biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of
Staphylococcus aureus
and
Candida glabrata
. The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.
Therapeutic Potential of the Mycobacterium tuberculosis Mycolic Acid Transporter, MmpL3
Authors: Li Wei , Obregón-Henao Andrés , Wallach Joshua B. , North E. Jeffrey , Lee Richard E. , Gonzalez-Juarrero Mercedes , Schnappinger Dirk , Jackson Mary 
Published: June 2016

ABSTRACT

In recent years, whole-cell-based screens for novel small molecule inhibitors active against
Mycobacterium tuberculosis
in culture followed by the whole-genome sequencing of spontaneous resistant mutants have identified multiple chemical scaffolds thought to kill the bacterium through the inactivation of the mycolic acid transporter, MmpL3. Consistent with the fact that MmpL3 is required for the formation of the mycobacterial outer membrane, we have conclusively shown in this study, using conditionally regulated knockdown mutants, that
mmpL3
is required for the replication and viability of
M. tuberculosis
, both under standard laboratory growth conditions and during the acute and chronic phases of infection in mice. Speaking for the vulnerability of this target, silencing
mmpL3
had a rapid bactericidal effect on actively replicating cells
in vitro
and reduced by 3 to 5 logs in less than 4 weeks the bacterial loads of acutely and chronically infected mouse lungs, respectively. Depletion of MmpL3 further rendered
M. tuberculosis
hypersusceptible to MmpL3 inhibitors. The exquisite vulnerability of MmpL3 at all stages of the infection establishes this transporter as an attractive new target with the potential to improve and shorten current drug-susceptible and drug-resistant tuberculosis chemotherapies.
Targeting the Cytochrome
bc
1
Complex of Leishmania Parasites for Discovery of Novel Drugs
Authors: Ortiz Diana , Forquer Isaac , Boitz Jan , Soysa Radika , Elya Carolyn , Fulwiler Audrey , Nilsen Aaron , Polley Tamsen , Riscoe Michael K. , Ullman Buddy , Landfear Scott M. 
Published: June 2016

ABSTRACT

Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome
bc
1
from
Plasmodium falciparum
and
Toxoplasma gondii
and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of
Leishmania
parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of
Leishmania mexicana
and
L. donovani
, with 50% inhibitory concentrations (IC
50
s) in the low micromolar range, but the structurally similar hydroxynaphthoquinone buparvaquone was by far the most potent inhibitor of electron transport, ATP production, and intracellular amastigote growth. Cytochrome
bc
1
is thus a promising target for novel antileishmanial drugs, and further improvements on the buparvaquone scaffold are warranted for development of enhanced therapeutics.
Microfilariae of Brugia malayi Inhibit the mTOR Pathway and Induce Autophagy in Human Dendritic Cells
Authors: Narasimhan Prakash Babu , Bennuru Sasisekhar , Meng Zhaojing , Cotton Rachel N. , Elliott Kathleen R. , Ganesan Sundar , McDonald-Fleming Renee , Veenstra Timothy D. , Nutman Thomas B. , Tolouei Semnani Roshanak 
Published: June 2016

ABSTRACT

Immune modulation is a hallmark of patent filarial infection, including suppression of antigen-presenting cell function and downmodulation of filarial antigen-specific T cell responses. The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in immune regulation, not only by suppressing T cell responses but also by regulating autophagy (through mTOR sensing amino acid availability). Global proteomic analysis (liquid chromatography-tandem mass spectrometry) of microfilaria (mf)-exposed monocyte-derived dendritic cells (DC) indicated that multiple components of the mTOR signaling pathway, including mTOR, eIF4A, and eIF4E, are downregulated by mf, suggesting that mf target this pathway for immune modulation in DC. Utilizing Western blot analysis, we demonstrate that similar to rapamycin (a known mTOR inhibitor), mf downregulate the phosphorylation of mTOR and its regulatory proteins, p70S6K1 and 4E-BP1, a process essential for DC protein synthesis. As active mTOR signaling regulates autophagy, we examined whether mf exposure alters autophagy-associated processes. mf-induced autophagy was reflected in marked upregulation of phosphorylated Beclin 1, known to play an important role in both autophagosome formation and autolysosome fusion, in induction of LC3II, a marker of autophagosome formation, and in induced degradation of p62, a ubiquitin-binding protein that aggregates protein in autophagosomes and is degraded upon autophagy that was reduced significantly by mf exposure and by rapamycin. Together, these results suggest that
Brugia malayi
mf employ mechanisms of metabolic modulation in DC to influence the regulation of the host immune response by downregulating mTOR signaling, resulting in increased autophagy. Whether this is a result of the parasite-secreted rapamycin homolog is currently under study.
NLRP3 Inflammasome Activation in THP-1 Target Cells Triggered by Pathogenic Naegleria fowleri
Authors: Kim Jong-Hyun , Sohn Hae-Jin , Yoo Jong-Kyun , Kang Heekyoung , Seong Gi-Sang , Chwae Yong-Joon , Kim Kyongmin , Park Sun , Shin Ho-Joon 
Published: June 2016

ABSTRACT

Naegleria fowleri
, known as the brain-eating amoeba, causes acute primary amoebic meningoencephalitis. During swimming and other recreational water activities,
N. fowleri
trophozoites penetrate the nasal mucosa and invade the olfactory bulbs, resulting in intense inflammatory reactions in the forebrain tissue. To investigate what kinds of inflammasome molecules are expressed in target cells due to
N. fowleri
infection, human macrophage cells (THP-1 cells) were cocultured with
N. fowleri
trophozoites in a noncontact system, and consequently, interleukin-1β (IL-1β) production was estimated. Caspase-1 activation and IL-1β production from THP-1 cells by Western blotting and the culture supernatant by enzyme-linked immunosorbent assay analysis were observed at 3 h after cocultivation. In addition, the increased expression of ASC and NLRP3, which make up an inflammasome complex, was also observed at 3 h after cocultivation. To confirm the caspase-1 activation and IL-1β production via the NLRP3 inflammasome in THP-1 cells triggered by
N. fowleri
trophozoites, THP-1 cells were pretreated with several inhibitors. The inhibition assay showed that CA-074 (a cathepsin B inhibitor), glybenclamide (an NLRP3 molecule inhibitor), and
N
-benzyloxycarbony-Val-Ala-Asp(
O
-methyl)-fluoromethylketone (Z-VAD-FMK; a caspase-1 inhibitor) reduced the levels of caspase-1 activation and IL-1β production from THP-1 cells. This study suggests that
N. fowleri
infection induces the NLRP3 inflammasome, which activates caspase-1 and subsequently produces IL-1β, thus resulting in inflammation.
Interleukin-8, CXCL1, and MicroRNA miR-146a Responses to Probiotic Escherichia coli Nissle 1917 and Enteropathogenic E. coli in Human Intestinal Epithelial T84 and Monocytic THP-1 Cells after Apical or Basolateral Infection
Authors: Sabharwal Harshana , Cichon Christoph , Ölschläger Tobias A. , Sonnenborn Ulrich , Schmidt M. Alexander 
Published: June 2016

ABSTRACTBacterium-host interactions in the gut proceed via directly contacted epithelial cells, the host's immune system, and a plethora of bacterial factors. Here we characterized and compared exemplary cytokine and microRNA (miRNA) responses of human epithelial and THP-1 cells toward the prototype enteropathogenicEscherichia coli(EPEC) strain E2348/69 (O127:H6) and the probiotic strainEscherichia coliNissle 1917 (EcN) (O6:K5:H1). Human T84 and THP-1 cells were used as cell culture-based model systems for epithelial and monocytic cells. Polarized T84 monolayers were infected apically or basolaterally. Bacterial challenges from the basolateral side resulted in more pronounced cytokine and miRNA responses than those observed for apical side infections. Interestingly, the probiotic EcN also caused a pronounced transcriptional increase of proinflammatory CXCL1 and interleukin-8 (IL-8) levels when human T84 epithelial cells were infected from the basolateral side. miR-146a, which is known to regulate adaptor molecules in Toll-like receptor (TLR)/NF-κB signaling, was found to be differentially regulated in THP-1 cells between probiotic and pathogenic bacteria. To assess the roles of flagella and flagellin, we employed several flagellin mutants of EcN. EcN flagellin mutants induced reduced IL-8 as well as CXCL1 responses in T84 cells, suggesting that flagellin is an inducer of this cytokine response. Following infection with an EPEC type 3 secretion system (T3SS) mutant, we observed increased IL-8 and CXCL1 transcription in T84 and THP-1 cells compared to that in wild-type EPEC. This study emphasizes the differential induction of miR-146a by pathogenic and probioticE. colistrains in epithelial and immune cells as well as a loss of probiotic properties in EcN interacting with cells from the basolateral side.