bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent emergency department visitors are frequent primary care visitors and report unmet primary care needs
Authors: Cunningham Amy , Mautner Dawn , Ku Bon , Scott Kevin , LaNoue Marianna 
Published: November 2016

AbstractA small percentage of emergency department (ED) visitors account for a disproportionate portion of ED visits. Little is known about their relationships with their primary care providers (PCPs). This study compares frequent and infrequent ED visitors' primary care utilization and perceptions of primary care access, continuity, and connectedness and examines primary care utilization and perceptions as predictors of ED use. Data were obtained from 2 cross‐sectional studies of psychosocial predictors of high levels of utilization at 2 urban hospitals. Data included age, sex, race/ethnicity, number and type of chronic conditions, self‐rated health, and number of primary care and ED visits in the previous 12 months. Participants also answered 8 primary care access, continuity, and connectedness items. Participants with frequent ED visits (N = 70) were younger (43.24 vs 48.34, P = .020), more likely to be African American (61.4% vs 41.8%, P < .001), had a significant chronic illness burden (5.83 vs 2.83 chronic conditions, P < .001), and were more likely to report fair or poor health (65.7% vs 50.4%, P = .009). Frequent ED users were as likely as infrequent users to have a usual source of care, and reported similar primary care access, relationship length, and likelihood of provider knowing them well. Although making twice as many primary care visits, these participants were less likely to report that they could get what they need from their PCP (76.12% vs 92.53%, P < .001). Despite similar primary care access and continuity, frequent ED visitors are less likely to report that they get what they need from their PCPs. Further research should investigate their needs and how primary care can best provide high‐value care to this complex population.
Margatoxin‐bound quantum dots as a novel inhibitor of the voltage‐gated ion channel Kv1.3
Authors: Schwartz Austin B. , Kapur Anshika , Wang Wentao , Huang Zhenbo , Fardone Erminia , Palui Goutam , Mattoussi Hedi , Fadool Debra Ann 
Published: November 2016

AbstractVenom‐derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage‐dependent potassium channel, Kv1.3, which has a select distribution and well‐characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD‐MgTx) for their ability to inhibit Shaker channels Kv1.1 to Kv1.7 using patch‐clamp electrophysiology in HEK293 cells. Our data indicate that MgTx inhibits 79% of the outward current in Kv1.3‐transfected cells and that the QD‐MgTx conjugate is able to achieve a similar level of block, albeit a slightly reduced efficacy (66%) and at a slower time course (50% block by 10.9 ± 1.1 min, MgTx; vs. 15.3 ± 1.2 min, QD‐MgTx). Like the unbound peptide, the QD‐MgTx conjugate inhibits both Kv1.3 and Kv1.2 at a 1 nM concentration, whereas it does not inhibit other screened Shaker channels. We tested the ability of QD‐MgTx to inhibit native Kv1.3 expressed in the mouse olfactory bulb (OB). In brain slices of the OB, the conjugate acted similarly to MgTx to inhibit Kv1.3, causing an increased action potential firing frequency attributed to decreased intraburst duration rather than interspike interval. Our data demonstrate a retention of known biophysical properties associated with block of the vestibule of Kv1.3 by QD‐MgTx conjugate compared to that of MgTx, inferring QDs could provide a useful tool to deliver ion channel inhibitors to targeted tissues in vivo.
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Attenuation of experimental autoimmune neuritis with locally administered lovastatin‐encapsulating poly(lactic‐co‐glycolic) acid nanoparticles
Authors: Langert Kelly A. , Goshu Bruktawit , Stubbs Evan B. 
Published: November 2016

AbstractAcute inflammatory demyelinating polyneuropathy (AIDP) is an aggressive antibody‐ and T‐cell‐mediated variant of Guillain–Barré Syndrome (GBS), a prominent and debilitating autoimmune disorder of the peripheral nervous system. Despite advancements in clinical management, treatment of patients with AIDP/GBS and its chronic variant CIDP remains palliative and relies on the use of non‐specific immunemodulating therapies. Our laboratory has previously reported that therapeutic administration of statins safely attenuates the clinical severity of experimental autoimmune neuritis (EAN), a well‐characterized animal model of AIDP/GBS, by restricting the migration of autoreactive leukocytes across peripheral nerve microvascular endoneurial endothelial cells that form the blood–nerve barrier. Despite these advancements, the clinical application of systemically administered statins for the management of inflammatory disorders remains controversial as a result of disappointingly inconclusive phase trials. Here, poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles were evaluated as an alternative strategy by which to locally administer statins for the management of EAN. When tested in vitro, lovastatin‐encapsulating PLGA nanoparticles elicited a marked increase in RhoB mRNA content in peripheral nerve microvascular endoneurial endothelial cells, similar to cells treated with activated unencapsulated lovastatin. Unilateral peri‐neural administration of lovastatin‐encapsulating PLGA nanoparticles, but not empty nanoparticles, to naïve Lewis rats similarly enhanced RhoB mRNA content in adjacent nerve and muscle tissue. When administered in this manner, serum levels of lovastatin were below the level of detection. Bilateral peri‐neural administration of lovastatin‐encapsulating PLGA nanoparticles to EAN‐induced Lewis rats significantly attenuated EAN clinical severity while protecting against EAN‐induced peripheral nerve morphological and functional deficits. This study provides the first proof‐of‐concept approach for the application of a nanoparticle‐based local drug delivery platform for the management of inflammatory demyelinating diseases, including AIDP/GBS.
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A PTS EII mutant library in Group A Streptococcus identifies a promiscuous man‐family PTS transporter influencing SLS‐mediated hemolysis
Authors: Sundar Ganesh S. , Islam Emrul , Gera Kanika , Le Breton Yoann , McIver Kevin S. 
Published: November 2016

SummaryThe Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram‐positive human pathogen that must adapt to unique host environments in order to survive. Links between sugar metabolism and virulence have been demonstrated in GAS, where mutants in the phosphoenolpyruvate‐dependent phosphotransferase system (PTS) exhibited Streptolysin S (SLS)‐mediated hemolysis during exponential growth. This early onset hemolysis correlated with an increased lesion size and severity in a murine soft tissue infection model when compared with parental M1T1 MGAS5005. To identify the PTS components responsible for this phenotype, we insertionally inactivated the 14 annotated PTS EIIC‐encoding genes in the GAS MGAS5005 genome and subjected this library to metabolic and hemolysis assays to functionally characterize each EIIC. It was found that a few EIIs had a very limited influence on PTS sugar metabolism, whereas others were fairly promiscuous. The mannose‐specific EII locus, encoded by manLMN, was expressed as a mannose‐inducible operon that exhibited the most influence on PTS sugar metabolism, including mannose. Importantly, components of the mannose‐specific EII also acted to prevent the early onset of SLS‐mediated hemolysis. Interestingly, these roles were not identical in two different M1T1 GAS strains, highlighting the possible versatility of the PTS to adapt to strain‐specific needs.
Pimpinella anisum L. ethanolic extract ameliorates the gentamicin‐ induced nephrotoxicity in rats
Authors: Changizi‐Ashtiyani Saeed , Seddigh Amirhassan , Najafi Houshang , Hossaini Nasser , Avan Amir , Akbary Ahmad , Manian Mostafa , Nedaeinia Reza 
Published: November 2016

AbstractAimGentamicin (GM) is one of the commonest causes of drug‐induced nephrotoxicity. Moreover, oxidative stress plays an important role in gentamicin‐induced nephrotoxicity. The current study aimed to explore the antioxidant and protective effects of Pimpinella anisum (P. anisum) on the alleviation of GM‐induced damage.MethodsForty male wistar rats were divided into four groups: control, sham that was administrated normal saline orally and intraperitoneally (i.p.), GM that received 100 mg/kg bw/day i.p., GM and ethanolic extract of P. anisum that was administrated at an oral dose of 300 mg/kg bw/day for 8 days. Creatinine, Na+, K+ and blood urea nitrogen (BUN) levels were measured. The levels of ferric‐reducing‐antioxidant‐power (FRAP) and malondialdehyde (MDA) were measured to evaluate the oxidative stress induced by GM. Kidney tissues were stained to determine the degree of tissue damage.ResultsThe plasma levels of creatinine, BUN, MDA and the absolute excretion of sodium and potassium were increased in the GM group, while FRAP level was reduced compared to the sham group. In addition, congestion of renal Vessels and tubular cell necrosis was observed. We found that 300 mg/kg bw/day P. anisum significantly reduced the plasma concentrations of renal function markers in the group receiving GM (P < 0.05). Additionally, gentamicin‐induced tubule damage was improved by P. anisum.ConclusionWe demonstrated the potential therapeutic impact of P. anisum to attenuate GM‐induced nephrotoxicity. Therefore, the simultaneous use of ethanolic extract of P. anisum during GM administration is recommended to reduce its nephrotoxicity effects.
Matrix metalloproteinase‐12 deficiency attenuates experimental crescentic anti‐glomerular basement membrane glomerulonephritis
Authors: Abraham Abu P. , Ma Frank Y. , Mulley William R. , Nikolic‐Paterson David J. , Tesch Greg H. 
Published: November 2016

AbstractAimMatrix metalloproteinase‐12 (MMP‐12; macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP‐12 is highly up‐regulated in experimental anti‐glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP‐12 is required for glomerular macrophage infiltration and crescent formation in anti‐GBM glomerulonephritis.MethodsAccelerated anti‐GBM disease was induced in groups of MMP‐12 gene deficient mice (MMP‐12−/−) and wild‐type C57BL/6J controls, which were killed 12 days after injection of anti‐GBM serum.ResultsWild‐type and MMP‐12−/− mice developed glomerular damage and glomerular tuft adhesions to Bowman's capsule. Both groups developed severe proteinuria. Wild‐type mice also developed significant loss of renal function and crescents in 22% of glomeruli, which were associated with macrophage infiltration and Bowman's capsule rupture. In contrast, MMP‐12−/− mice were partially protected from renal function decline, crescent formation and Bowman's capsule rupture. This was associated with reduced macrophage infiltration in both glomeruli and the interstitium, and with reduced expression of CCL2, TNF‐α and iNOS mRNA in MMP‐12−/− kidneys. In addition, KIM‐1 mRNA levels were reduced in MMP‐12−/− mice indicating less tubular damage.ConclusionThese data demonstrate that endogenous MMP‐12 facilitates macrophage accumulation and activation in anti‐GBM glomerulonephritis which is required for glomerular crescent formation, Bowman's capsule rupture, tubular damage and renal function decline.
Barriers and facilitators to the implementation of person‐centred care in different healthcare contexts
Authors: Moore Lucy , Britten Nicky , Lydahl Doris , Naldemirci Öncel , Elam Mark , Wolf Axel 
Published: November 2016

BackgroundTo empower patients and improve the quality of care, policy‐makers increasingly adopt systems to enhance person‐centred care. Although models of person‐centredness and patient‐centredness vary, respecting the needs and preferences of individuals receiving care is paramount. In Sweden, as in other countries, healthcare providers seek to improve person‐centred principles and address gaps in practice. Consequently, researchers at the University of Gothenburg Centre for Person‐Centred Care are currently delivering person‐centred interventions employing a framework that incorporates three routines. These include eliciting the patient's narrative, agreeing a partnership with shared goals between patient and professional, and safeguarding this through documentation.AimTo explore the barriers and facilitators to the delivery of person‐centred care interventions, in different contexts.MethodQualitative interviews were conducted with a purposeful sample of 18 researchers from seven research studies across contrasting healthcare settings. Interviews were transcribed, translated and thematically analysed, adopting some basic features of grounded theory.Ethical issuesThe ethical code of conduct was followed and conformed to the ethical guidelines adopted by the Swedish Research Council.ResultsBarriers to the implementation of person‐centred care covered three themes: traditional practices and structures; sceptical, stereotypical attitudes from professionals; and factors related to the development of person‐centred interventions. Facilitators included organisational factors, leadership and training and an enabling attitude and approach by professionals. Trained project managers, patients taking an active role in research and adaptive strategies by researchers all helped person‐centred care delivery.ConclusionAt the University of Gothenburg, a model of person‐centred care is being initiated and integrated into practice through research. Knowledgeable, well‐trained professionals facilitate the routines of narrative elicitation and partnership. Strong leadership and adaptive strategies are important for overcoming existing practices, routines and methods of documentation. This study provides guidance for practitioners when delivering and adapting person‐centred care in different contexts.
HT proteins contribute to S‐RNase‐independent pollen rejection in Solanum
Authors: Tovar‐Méndez Alejandro , Lu Lu , McClure Bruce 
Published: November 2016

SummaryPlants have mechanisms to recognize and reject pollen from other species. Although widespread, these mechanisms are less well understood than the self‐incompatibility (SI) mechanisms plants use to reject pollen from close relatives. Previous studies have shown that some interspecific reproductive barriers (IRBs) are related to SI in the Solanaceae. For example, the pistil SI proteins S‐RNase and HT protein function in a pistil‐side IRB that causes rejection of pollen from self‐compatible (SC) red/orange‐fruited species in the tomato clade. However, S‐RNase‐independent IRBs also clearly contribute to rejecting pollen from these species. We investigated S‐RNase‐independent rejection of Solanum lycopersicum pollen by SC Solanum pennellii LA0716, SC. Solanum habrochaites LA0407, and SC Solanum arcanum LA2157, which lack functional S‐RNase expression. We found that all three accessions express HT proteins, which previously had been known to function only in conjunction with S‐RNase, and then used RNAi to test whether they also function in S‐RNase‐independent pollen rejection. Suppressing HT expression in SC S. pennellii LA0716 allows S. lycopersicum pollen tubes to penetrate farther into the pistil in HT suppressed plants, but not to reach the ovary. In contrast, suppressing HT expression in SC. Solanum habrochaites LA0407 and in SC S. arcanum LA2157 allows S. lycopersicum pollen tubes to penetrate to the ovary and produce hybrids that, otherwise, would be difficult to obtain. Thus, HT proteins are implicated in both S‐RNase‐dependent and S‐RNase‐independent pollen rejection. The results support the view that overall compatibility results from multiple pollen–pistil interactions with additive effects.
COMPARATIVE STUDY ON THE THERMAL ENVIRONMENTAL RESPONSES OF INDIGENOUS BAMBOO AND MODERN BRICK HOUSES IN HOT-HUMID CLIMATE OF MALAYSIA
Authors: Dahlan Nur Dalilah , Ghaffarianhoseini Amirhosein 
Published: November 2016

Vernacular houses using indigenous building materials have shown to be a good strategy for sustainable energy consumption without compensating the occupant’s indoor thermal comfort. Bamboo has been identified as the most used building material for vernacular houses in South-East Asia region. However, very little investigation has been conducted to study the passive performance of a bamboo house in maintaining indoor thermal comfort. This study compares the indoor microclimate conditions using thermal comfort Predicted Mean Vote and Predicted Percentage of Dissatisfied models (PMV-PPD) developed by American Society Heating, Refrigerating and Air-conditioning Engineers (ASHRAE) between indigenous bamboo house (H1) and modern brick house (H2) at a village located in the Ulu Gombak Forest Reserve, Selangor. Observations on environmental factors and predicted thermal comfort satisfaction level between day and night times were also taken into consideration. The findings suggest that the use of bamboo plus other vernacular house design features such as raising a house on stilts, located on hilly site and providing air permeability in H1 can lead to a thermally comfortable indoor environment, particularly during night time.
Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling
Authors: Yadav Rajbharan , Bulitta Jürgen B. , Nation Roger L. , Landersdorfer Cornelia B. 
Published: November 2016

ABSTRACT

Optimizing antibiotic combinations is promising to combat multidrug-resistant
Pseudomonas aeruginosa
. This study aimed to systematically evaluate synergistic bacterial killing and prevention of resistance by carbapenem and aminoglycoside combinations and to rationally optimize combination dosage regimens via a mechanism-based mathematical model (MBM). We studied monotherapies and combinations of imipenem with tobramycin or amikacin against three difficult-to-treat double-resistant clinical
P. aeruginosa
isolates. Viable-count profiles of total and resistant populations were quantified in 48-h static-concentration time-kill studies (inoculum, 10
7.5
CFU/ml). We rationally optimized combination dosage regimens via MBM and Monte Carlo simulations against isolate FADDI-PA088 (MIC of imipenem [MIC
imipenem
] of 16 mg/liter and MIC
tobramycin
of 32 mg/liter, i.e., both 98th percentiles according to the EUCAST database). Against this isolate, imipenem (1.5× MIC) combined with 1 to 2 mg/liter tobramycin (MIC, 32 mg/liter) or amikacin (MIC, 4 mg/liter) yielded ≥2-log
10
more killing than the most active monotherapy at 48 h and prevented resistance. For all three strains, synergistic killing without resistance was achieved by ≥0.88× MIC
imipenem
in combination with a median of 0.75× MIC
tobramycin
(range, 0.032× to 2.0× MIC
tobramycin
) or 0.50× MIC
amikacin
(range, 0.25× to 0.50× MIC
amikacin
). The MBM indicated that aminoglycosides significantly enhanced the imipenem target site concentration up to 3-fold; achieving 50% of this synergistic effect required aminoglycoside concentrations of 1.34 mg/liter (if the aminoglycoside MIC was 4 mg/liter) and 4.88 mg/liter (for MICs of 8 to 32 mg/liter). An optimized combination regimen (continuous infusion of imipenem at 5 g/day plus a 0.5-h infusion with 7 mg/kg of body weight tobramycin) was predicted to achieve >2.0-log
10
killing and prevent regrowth at 48 h in 90.3% of patients (median bacterial killing, >4.0 log
10
CFU/ml) against double-resistant isolate FADDI-PA088 and therefore was highly promising.
Bacterial Replication Rate Modulation in Combination with Antimicrobial Therapy: Turning the Microbe against Itself
Authors: Ambrose Paul G. , VanScoy Brian , Conde Haley , McCauley Jennifer , Rubino Christopher M. , Bhavnani Sujata M. 
Published: November 2016

ABSTRACT

A major clinical challenge for treating infectious diseases is the duration of antimicrobial therapy required to eradicate the pathogen. We hypothesized that modulation of the bacterial replication rate in the context of an antimicrobial exposure is coupled with the rate and extent of bactericidal effects. Herein we describe results from
in vitro
infection model (one compartment, 24-h model; hollow fiber, 10-day model) studies designed to probe the relationship between the bacterial replication rate and the rate and extent of bactericidal effects in the context of an effective antibiotic exposure. The bacterial replication rate was modulated by adjusting the sodium chloride concentration (0 to 8%) in the growth media (Mueller-Hinton II broth). The study drug selected was levofloxacin, and the challenge isolate was
Staphylococcus aureus
ATCC 29213 (levofloxacin MIC, 0.125 mg/liter). Within each
in vitro
infection model, human levofloxacin concentration-time profiles (half-life, 7 h) were simulated and the challenge isolate was subjected to an effective exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC ratio], 65; administered as a single dose or daily for 10 days). Over the course of each study, samples were taken from each model for bacterial density determinations and drug concentration assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the 24-h one-compartment
in vitro
infection model studies, as the bacterial replication rate increased, so too did the rate (slope, 0 to 4 h) and extent (24-h CFU count per milliliter) of bacterial killing. In the 10-day hollow-fiber infection model studies, the times until a reduction of bacterial density to 1 × 10
2
CFU/ml occurred were 10 days in the media in which the challenge isolate grew slowly and approximately 2 days in the media in which the challenge isolate grew rapidly. Together, these data provide a proof of concept for new adjunctive therapeutic options with respect to the use of antimicrobial agents alone that reduce treatment durations. Such adjunctive therapies hold promise for marked reductions in the tonnage of antimicrobial agents administered to patient populations and selection pressure toward antimicrobial resistance.
Activity of Electrical Current in Experimental Propionibacterium acnes Foreign-Body Osteomyelitis
Authors: Schmidt-Malan Suzannah M. , Brinkman Cassandra L. , Greenwood-Quaintance Kerryl E. , Karau Melissa J. , Mandrekar Jayawant N. , Patel Robin 
Published: November 2016

ABSTRACT

Foreign-body-associated infections are often difficult to treat, given that the associated microorganisms are in a biofilm state. Previously, we showed that a low-amperage direct electrical current (DC) reduces
Propionibacterium acnes
biofilms formed on implant-associated materials
in vitro
. In this study, low-amperage DC was compared to ceftriaxone treatment or no treatment in a novel rat femur model of foreign-body osteomyelitis. A platinum implant seeded with a
P. acnes
biofilm (10
7
CFU/cm
2
) and 10
9
CFU of planktonic
P. acnes
was placed in the femoral medullary cavity. One week later, rats were assigned to one of three treatment groups: no treatment, ceftriaxone treatment, or 200-μA-DC treatment. After 2 weeks of treatment, there were fewer bacteria in the bones of the ceftriaxone group (3.06 log
10
CFU/g of bone [
P
= 0.0209]) and the 200-μA-DC group (0.5 log
10
CFU/g [
P
= 0.0015]) than in those of the control group (6.58 log
10
CFU/g). The DC-exposed animals exhibited fewer bacteria than the ceftriaxone-treated animals (
P
= 0.0330). There were fewer bacteria on the implanted wires in the groups treated with ceftriaxone (0.1 log
10
CFU/cm
2
) or a 200-μA DC (0.1 log
10
CFU/cm
2
) than in the control group (2.53 log
10
CFU/cm
2
[
P
, 0.0003 for both comparisons]). Low-amperage DC may be useful for treating, or aiding in the treatment of, foreign-body infections caused by
P. acnes
.