bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of isometric handgrip testing on left ventricular twist mechanics
Authors: Weiner Rory B. , Weyman Arthur E. , Kim Jonathan H. , Wang Thomas J. , Picard Michael H. , Baggish Aaron L. 
Published: August 2012

Key points
Left ventricular twist (LVT) results from rotation of the LV apex and base in opposite directions.
Although LVT is altered in various cardiac diseases, physiological factors that affect LVT remain incompletely understood.
In an experimental model involving healthy humans, isometric handgrip testing (IHGT) was performed to produce a clinically relevant form of LV afterload increase. The impact of IHGT on LV twist mechanics was assessed using speckle‐tracking echocardiography.
IHGT produced significant increase in systemic blood pressure and acute reduction in LV stroke volume. In this setting, LV apical rotation and LVT significantly decreased.
Impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload.
Abstract  Left ventricular (LV) rotation occurs due to contraction of obliquely oriented myocardial fibres. Left ventricular twist (LVT) results from rotation of the apex and base in opposite directions. Although LVT is altered in various cardiac diseases, physiological factors that affect LVT remain incompletely understood. Isometric handgrip testing (IHGT), a well‐established laboratory‐based technique to increase LV afterload, was performed for 3 min at 40% maximum force generation in healthy human subjects (n= 18, mean age 29.7 ± 2.7 years). Speckle‐tracking echocardiography was used to measure LV volumes, LV apical and basal rotation, peak systolic LVT and peak early diastolic untwisting rate (UTR) at rest and at peak IHGT. IHGT led to significant increase in systemic blood pressure (systolic, 120.6 ± 9.7 vs. 155.6 ± 14.5 mmHg, P < 0.001; diastolic, 67.5 ± 6.4 vs. 94.1 ± 21.1 mmHg, P < 0.001) and LV end‐systolic volume (44.2 ± 7.8 vs. 50.5 ± 10.8 ml, P= 0.005), as well as a significant increase in heart rate (62.8 ± 11.7 vs. 84.7 ± 13.8 beats min−1; P < 0.001). IHGT produced a significant acute reduction in LV stroke volume (63.9 ± 12.0 vs. 49.4 ± 7.8 ml, P < 0.001). In this setting, there was a significant decrease in peak systolic apical rotation (11.9 ± 3.0 vs. 8.6 ± 2.2 deg, P < 0.001) and a resultant 25% decrease in peak systolic LVT (16.6 ± 2.8 vs. 12.5 ± 2.8 deg, P < 0.001). The magnitude of peak early diastolic UTR did not change (−114.5 ± 26.4 vs. −110.6 ± 39.8 deg s−1, P= 0.71). Peak systolic apical rotation and LVT decrease during IHGT in healthy humans. This impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload.
Mammalian prestin is a weak Cl−/HCO3− electrogenic antiporter
Authors: Mistrík P. , Daudet N. , Morandell K. , Ashmore J. F. 
Published: August 2012

Key points
Outer hair cells of the mammalian cochlea are cells which amplify the incoming sound using mechanisms based on prestin, a molecular actuator related to a family of chloride–bicarbonate exchangers.
It has not been clear so far whether prestin has any bicarbonate–chloride exchange properties, often being described as an ‘incomplete transporter’.
Here we show, using a pH probe linked to prestin in an expression system, that prestin can transport bicarbonate at low rates and acts as an electrogenic transporter for chloride.
The high expression level of prestin in mammalian outer hair cells thus accounts for a number of previous observations of the cells’ internal pH regulation, and may indicate an additional role for prestin in homeostatic regulation of cochlear amplification.
Abstract  The lateral membrane of mammalian cochlear outer hair cells contains prestin, a protein which can act as a fast voltage‐driven actuator responsible for electromotility and enhanced sensitivity to sound. The protein belongs to the SLC26 family of transporters whose members are characterised as able to exchange halides for SO42− or HCO3− yet previous analyses of mammalian prestin have suggested that such exchange functions were minimal. Here anion transport is investigated both in guinea‐pig outer hair cells (OHCs) and in an expression system where we employ a sensitive intracellular pH (pHi) probe, pHluorin, to report HCO3− transport and to monitor the small pHi changes observable in the cells. In the presence of extracellular HCO3−, pHi recovered from an acid load 4 times faster in prestin‐transfected cells. The acceleration required a chloride gradient established by reducing extracellular chloride to 2 mm. Similar results were also shown using BCECF as an alternative pHi sensor, but with recovery only found in those cells expressing prestin. Simultaneous electrophysiological recording of the transfected cells during bicarbonate exposure produced a shift in the reversal potential to more negative potentials, consistent with electrogenic transport. These data therefore suggest that prestin can act as a weak Cl−/HCO3− antiporter and it is proposed that, in addition to participating in wide band cochlear sound amplification, prestin may also be involved in the slow time scale (>10 s) phenomena where changes in cell stiffness and internal pressure have been implicated. The results show the importance of considering the effects of the endogenous bicarbonate buffering system in evaluating the function of prestin in cochlear outer hair cells.
Differential Modulation of Intracellular Survival of Cytosolic and Vacuolar Pathogens by Curcumin
Authors: Marathe Sandhya A. , Sen Minakshi , Dasgupta Ishani , Chakravortty Dipshikha 
Published: August 2012

ABSTRACT

Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of
Helicobacter pylori
infection and exacerbate that of
Leishmania
infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by
Shigella flexneri
(clinical isolates) and
Listeria monocytogenes
and aggravates those caused by
Salmonella enterica
serovar Typhi CT18 (a clinical isolate),
Salmonella enterica
serovar Typhimurium,
Staphylococcus aureus
, and
Yersinia enterocolitica
. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (
S. flexneri
and
L. monocytogenes
) and vacuolar (
Salmonella
spp.,
Y. enterocolitica
, and
S. aureus
) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria.
Utilization of Omeprazole To Augment Subtherapeutic Voriconazole Concentrations for Treatment of Aspergillus Infections
Authors: Boyd Natalie K. , Zoellner Cindy L. , Swancutt Mark A. , Bhavan Kavita P. 
Published: August 2012

ABSTRACT

Voriconazole is the preferred antifungal agent for
Aspergillus
infections. Therapeutic drug monitoring is recommended to achieve target concentrations and prevent toxicity. However, variable pharmacokinetics, cytochrome P450 polymorphisms, and extensive drug-drug interactions can contribute to subtherapeutic concentrations. We report a voriconazole “boosting” effect of omeprazole to achieve target concentrations for the treatment of
Aspergillus
in a patient who had persistently subtherapeutic trough concentrations.
Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting Concentration
Authors: Dolton Michael J. , Ray John E. , Chen Sharon C.-A. , Ng Kingsley , Pont Lisa , McLachlan Andrew J. 
Published: August 2012

ABSTRACT

Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml;
P
< 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (
P
< 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H
2
antagonist ranitidine (
P
< 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (
P
< 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure optimal systemic exposure.
Clinical Prediction of Failure of Lamivudine Prophylaxis for Hepatitis B Virus-Infected Patients Undergoing Cytotoxic Chemotherapy for Malignancy
Authors: Kim In Kyoung , Kim Byeong Gwan , Kim Won , Kim Donghee , Kim Yoon Jun , Yoon Jung-Hwan , Lee Hyo Suk 
Published: August 2012

ABSTRACT

Although lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray's model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94;
P
= 0.0063) and the use of rituximab (HR, 3.19;
P
= 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90;
P
= 0.007), liver cirrhosis (HR, 10.4;
P
= 0.002), and distant metastasis (HR, 5.14;
P
= 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance.
Telavancin in Therapy of Experimental Aortic Valve Endocarditis in Rabbits Due to Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus
Authors: Xiong Yan Q. , Hady Wessam Abdel , Bayer Arnold S. , Chen Liang , Kreiswirth Barry N. , Yang Soo-Jin 
Published: August 2012

ABSTRACT

A number of cases of both methicillin-susceptible
Staphylococcus aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA) strains that have developed daptomycin resistance (DAP-R) have been reported. Telavancin (TLV) is a lipoglycopeptide agent with a dual mechanism of activity (cell wall synthesis inhibition plus depolarization of the bacterial cell membrane). Five recent daptomycin-susceptible (DAP-S)/DAP-R MRSA isogenic strain pairs were evaluated for
in vitro
TLV susceptibility. All five DAP-R strains (DAP MICs ranging from 2 to 4 μg/ml) were susceptible to TLV (MICs of ≤0.38 μg/ml).
In vitro
time-kill analyses also revealed that several TLV concentrations (1-, 2-, and 4-fold MICs) caused rapid killing against the DAP-R strains. Moreover, for 3 of 5 DAP-R strains (REF2145, A215, and B
2.0
), supra-MICs of TLV were effective at preventing regrowth at 24 h of incubation. Further, the combination of TLV plus oxacillin (at 0.25× or 0.50× MIC for each agent) increased killing of DAP-R MRSA strains REF2145 and A215 at 24 h (∼2-log and 5-log reductions versus TLV and oxacillin alone, respectively). Finally, using a rabbit model of aortic valve endocarditis caused by DAP-R strain REF2145, TLV therapy produced a mean reduction of >4.5 log
10
CFU/g in vegetations, kidneys, and spleen compared to untreated or DAP-treated rabbits. Moreover, TLV-treated rabbits had a significantly higher percentage of sterile tissue cultures (87% in vegetations and 100% in kidney and spleen) than all other treatment groups (
P
< 0.0001). Together, these results demonstrate that TLV has potent bactericidal activity
in vitro
and
in vivo
against DAP-R MRSA isolates.
Antibacterial Activity of Joint Fluid in Cemented Total-Knee Arthroplasty: an
In Vivo
Comparative Study of Polymethylmethacrylate with and without Antibiotic Loading
Authors: Ueng Steve W. N. , Hsieh Pang-Hsin , Shih Hsin-Nung , Chan Yi-Shan , Lee Mel S. , Chang Yuhan 
Published: August 2012

ABSTRACT

The objective of this study was to evaluate the antibacterial activities of joint fluids of patients undergoing total-knee arthroplasty (TKA). Thirty patients who were scheduled for primary cemented TKA were enrolled in the study. The patients were grouped on the basis of whether the cement was without antibiotic loading (control group) or loaded with oxacillin (oxacillin group) or vancomycin (vancomycin group). Cefazolin was administered to every patient as the perioperative prophylactic antibiotic. Samples of joint fluids were collected from the knee joints at 8, 16, 24, 32, 40, and 48 h after prosthesis implantation. We assessed the bioactivities of the joint fluids against methicillin-susceptible
Staphylococcus aureus
(MSSA) and methicillin-resistant
S. aureus
(MRSA). The antibiotic contents of the joint fluid samples were further evaluated by using high-performance liquid chromatography. Against MSSA, all joint fluid samples exhibited at least 24 h of bacterial inhibition activity. The oxacillin (43.2 h ± 2 h) and vancomycin (40.8 h ± 1.8 h) groups exhibited significantly longer durations of antibacterial activities than the control group (28 h ± 1.3 h;
P
< 0.05). However, antibacterial activity against MRSA was observed only in the vancomycin group. In conclusion, cefazolin, which was administered as a prophylactic antibiotic in TKA, exhibited good ability for knee joint penetration and was sufficient to inhibit MSSA during its administration. The use of antibiotic-loaded cement can prolong the antibacterial activity of joint fluid in TKA. Further, vancomycin-loaded cement had antibacterial activity against MRSA superior to that of cement loaded with oxacillin or without antibiotic loading.
Risk Factors for Infection or Colonization with CTX-M Extended-Spectrum-β-Lactamase-Positive Escherichia coli
Authors: Han Jennifer H. , Kasahara Kei , Edelstein Paul H. , Bilker Warren B. , Lautenbach Ebbing 
Published: August 2012

ABSTRACT

There has been a significant increase in the prevalence of
Enterobacteriaceae
that produce CTX-M-type extended-spectrum β-lactamases. The objective of this study was to evaluate risk factors for infection or colonization with CTX-M-positive
Escherichia coli
. A case-control study was conducted within a university system from 1 January 2007 to 31 December 2008. All patients with clinical cultures with
E. coli
demonstrating resistance to extended-spectrum cephalosporins were included. Case patients were designated as those with cultures positive for CTX-M-positive
E. coli
, and control patients were designated as those with non-CTX-M-producing
E. coli
. Multivariable logistic regression analyses were performed to evaluate risk factors for CTX-M-positive isolates. A total of 83 (56.8%) of a total of 146 patients had cultures with CTX-M-positive
E. coli
. On multivariable analyses, there was a significant association between infection or colonization with CTX-M-type β-lactamase-positive
E. coli
and receipt of piperacillin-tazobactam in the 30 days prior to the culture date (odds ratio [OR], 7.36; 95% confidence interval [CI], 1.61 to 33.8;
P
= 0.01) and a urinary culture source (OR, 0.36; 95% CI, 0.17 to 0.77;
P
= 0.008). The rates of resistance to fluoroquinolones were significantly higher in isolates from case patients than in isolates from control patients (90.4 and 50.8%, respectively;
P
< 0.001). We found that nonurinary sources of clinical cultures and the recent use of piperacillin-tazobactam conferred an increased risk of colonization or infection with CTX-M-positive
E. coli
. Future studies will need to focus on outcomes associated with infections due to CTX-M-positive
E. coli
, as well as infection control strategies to limit the spread of these increasingly common organisms.
Prevalence and Significance of HIV-1 Drug Resistance Mutations among Patients on Antiretroviral Therapy with Detectable Low-Level Viremia
Authors: Li Jonathan Z. , Gallien Sebastien , Do Tri D. , Martin Jeffrey N. , Deeks Steven , Kuritzkes Daniel R. , Hatano Hiroyu 
Published: August 2012

ABSTRACTHIV-1 resistance testing was performed in 47 antiretroviral (ARV)-treated subjects with low-level viremia (LLV) of <1,000 copies/ml. The median viral load was 267 copies/ml. In those with ≥2 LLV episodes, 44% accumulated additional resistance mutations. Fewer active ARVs and longer elapsed time were associated with an increased risk of resistance accumulation after controlling for adherence and viral load. Virologic failure followed 16% of LLV time points. Strategies for early intervention after LLV episodes should be further studied.
Macrolides and β-Lactam Antibiotics Enhance C3b Deposition on the Surface of Multidrug-Resistant Streptococcus pneumoniae Strains by a LytA Autolysin-Dependent Mechanism
Authors: Ramos-Sevillano Elisa , Rodríguez-Sosa Cinthya , Díez-Martínez Roberto , Giménez María-José , Olmedillas Eduardo , García Pedro , García Ernesto , Aguilar Lorenzo , Yuste Jose 
Published: August 2012

ABSTRACT

The emergence of
Streptococcus pneumoniae
strains displaying high levels of multidrug resistance is of great concern worldwide and a serious threat for the outcome of the infection. Modifications of the bacterial envelope by antibiotics may assist the recognition and clearance of the pathogen by the host immune system. Recognition of
S. pneumoniae
resistant strains by the complement component C3b was increased in the presence of specific anti-pneumococcal antibodies and subinhibitory concentrations of different macrolides and β-lactam antibiotics for all the strains investigated. However, C3b levels were unchanged in the presence of serum containing specific antibodies and sub-MICs of levofloxacin. To investigate whether LytA, the main cell wall hydrolase of
S. pneumoniae
, might be involved in this process,
lytA
-deficient mutants were constructed. In the presence of antibiotics, loss of LytA was not associated with enhanced C3b deposition on the pneumococcal surface, which confirms the importance of LytA in this interaction. The results of this study offer new insights into the development of novel therapeutic strategies using certain antibiotics by increasing the efficacy of the host immune response to efficiently recognize pneumococcal resistant strains.
The Toll Interleukin-1 Receptor (IL-1R) 8/Single Ig Domain IL-1R-Related Molecule Modulates the Renal Response to Bacterial Infection
Authors: Leemans Jaklien C. , Butter Loes M. , Teske Gwendoline J. D. , Stroo Ingrid , Pulskens Wilco P. , Florquin Sandrine 
Published: August 2012

ABSTRACTOur immune system has to constantly strike a balance between activation and inhibition of an inflammatory response to combat invading pathogens and avoid inflammation-induced collateral tissue damage. Toll interleukin-1 receptor 8 (IL-1R-8)/single Ig domain IL-1R-related molecule (TIR8/SIGIRR) is an inhibitor of Toll-like receptor (TLR)/IL-1R signaling, which is predominantly expressed in the kidney. The biological role of renal TIR8 during infection is, however, unknown. We therefore evaluated renal TIR8 expression duringEscherichia colipyelonephritis and explored its role in host defense using TIR8−/−versus TIR8+/+mice. We found that TIR8 protein is abundantly present in the majority of cortical tubular epithelial cells. Pyelonephritis resulted in a significant downregulation of TIR8 mRNA in kidneys of TIR8+/+mice. TIR8 inhibited an effective host response againstE. coli, as indicated by diminished renal bacterial outgrowth and dysfunction in TIR8−/−mice. This correlated with increased amounts of circulating and intrarenal neutrophils at the early phase of infection. TIR8−/−tubular epithelial cells had increased cytokine/chemokine production when stimulated with lipopolysaccharide (LPS) or heat-killedE. coli, suggesting that TIR8 played an anti-inflammatory role during pathogen stimulation by inhibiting LPS signaling. These data suggest that TIR8 is an important negative regulator of an LPS-mediated inflammatory response in tubular epithelial cells and dampens an effective antibacterial host response during pyelonephritis caused by uropathogenicE. coli.
Uptake and Persistence of Mycobacterium avium subsp. paratuberculosis in Human Monocytes
Authors: Keown Dayle A. , Collings David A. , Keenan Jacqueline I. 
Published: August 2012

ABSTRACT

Mycobacterium avium
subsp.
paratuberculosis
is a bacterium sometimes found in human blood and tissue samples that may have a role in the etiology of Crohn's disease in humans. To date, however, there have been few studies examining the interactions of these bacteria with human cells. Using the THP-1 human monocytic cell line, this study shows that the uptake and trafficking of
M. avium
subsp.
paratuberculosis
in human cells are cholesterol dependent and that these bacteria localize to cholesterol-rich compartments that are slow to acidify.
M. avium
subsp.
paratuberculosis
bacteria containing phagosomes stain for the late endosomal marker Rab7, but recruitment of the Rab7-interacting lysosomal protein that regulates the fusion of bacterium-containing phagosomes with lysosomal compartments and facilitates subsequent bacterial clearance is significantly reduced. Disruption of phagosome acidification via this mechanism may contribute to
M. avium
subsp.
paratuberculosis
persistence in human cells, but there was no evidence that internalized
M. avium
subsp.
paratuberculosis
also affects the survival of bacteria taken up during a secondary phagocytic event.