bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement in left intraventricular pressure gradients after aortic valve replacement in aortic stenosis patients
Authors: Guerra Miguel , Mendes‐Ferreira Pedro , Adão Rui , Pereira Eulália , Vieira Manuela , Lourenço André P. , Brás‐Silva Carmen , Bastos Pedro , Vouga Luís , Leite‐Moreira Adelino F. 
Published: February 2017

New Findings
What is the central question of this study?
Normal diastolic and systolic intraventricular pressure gradients are decreased when left ventricular filling and/or emptying are compromised. We hypothesized that in patients with severe aortic valve stenosis, a condition that interferes with ventricular filling and emptying, those gradients would be disturbed.

What is the main finding and its importance?
We showed the existence of intraventricular pressure gradients throughout the cardiac cycle in the human left ventricle. Moreover, we demonstrated, for the first time, that diastolic and systolic gradients, which are markers of normal ventricular filling and emptying, respectively, improved in patients with severe aortic valve stenosis immediately after valve replacement.

The present study was conducted to characterize left intraventicular pressure gradients, which are markers of normal cardiac function, in patients with severe aortic stenosis, a condition that interferes with ventricular filling and emptying. In 10 patients (four male; mean age 71.3 ± 4.8 years old) undergoing aortic valve replacement, two high‐fidelity pressure catheters were inserted inside the cavity of the left ventricle through an apical puncture and positioned in the apex and outflow tract below the aortic valve. Pressures were continuously acquired and gradients calculated as apical minus outflow tract pressure, before and immediately after aortic valve replacement. During early filling, we recorded a negative intraventricular gradient along the basal portion of the left ventricle in the apical direction (−0.82 ± 0.45 mmHg), which increased to −3.97 ± 0.42 mmHg after aortic valve replacement. In late filling, intraventricular flow was now directed towards the outflow tract, with a positive pressure gradient both before (+1.23 ± 0.37 mmHg) and after surgery (+2.12 ± 0.58 mmHg). During systole, before surgery we observed a positive pressure gradient between the apex and outflow tract during both rapid (+1.60 ± 0.21 mmHg) and slow ejection phases (+1.68 ± 0.12 mmHg), whereas after aortic valve replacement the positive gradient (+1.54 ± 0.15 mmHg) during rapid ejection was inverted (−3.92 ± 0.34 mmHg) during the slow ejection phase. We demonstrated that in patients with severe aortic stenosis both diastolic and systolic intraventricular pressure gradients are significantly attenuated but can be restored immediately after aortic valve replacement. The assessment and measurement of intraventricular pressure gradients and their modulation in pathophysiological conditions may provide novel insights into cardiac physiology.
Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency
Authors: Limesand Sean W. , Rozance Paul J. 
Published: February 2017

AbstractPlacental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short‐ and long‐term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β‐cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7‐day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin‐stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants.
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Determining the Clinical Utility of an Absolute Procalcitonin Value for Predicting a Positive Culture Result
Authors: Caffarini Erica M. , DeMott Joshua , Patel Gourang , Lat Ishaq 
Published: February 2017

ABSTRACT
Various procalcitonin ranges have been established to guide antimicrobial therapy; however, there are no data that establish whether the initial procalcitonin value can determine the likelihood of a positive culture result. This study aimed to establish if the initial procalcitonin value, on clinical presentation, has a positive predictive value for any positive culture result. This was a retrospective study of 813 medical intensive care unit patients. Data collected included patient demographics, procalcitonin assay results, sources of infection, culture results, and lengths of stay. Patients were excluded if they were immunocompromised. The primary outcome of this study was to determine a procalcitonin value that would predict any positive culture. Secondary outcomes included the sensitivity, specificity, positive predictive value, and negative predictive value for procalcitonin. After exclusions, a total of 519 patient charts were reviewed to determine the impact of the initial procalcitonin value on culture positivity. In our analyses, the receiver operating characteristic values were 0.62 for all cultures, 0.49 for pulmonary infections, 0.43 for urinary tract infections, and 0.78 for bacteremia. A procalcitonin value of 3.61 ng/ml was determined to be the threshold value for a positive blood culture result (prevalence, 4%). For bacteremia, the sensitivity of procalcitonin was 75%, the specificity was 72%, the positive predictive value was 20%, and the negative predictive value was 97%. Procalcitonin was a poor predictor of culture positivity. An initial procalcitonin value of less than 3.61 ng/ml may be useful in predicting whether bacteremia is absent. Procalcitonin should not be used as the only predictor for determining initiation of antibiotic therapy.
In Vivo
Pharmacodynamic Evaluation of Omadacycline (PTK 0796) against Streptococcus pneumoniae in the Murine Pneumonia Model
Authors: Lepak Alexander J. , Zhao Miao , Marchillo Karen , VanHecker Jamie , Andes David R. 
Published: February 2017

ABSTRACT

Omadacycline is a novel aminomethylcycline antibiotic in clinical development for community-acquired bacterial pneumonia (CABP). We used a neutropenic murine pneumonia infection model to characterize the
in vivo
pharmacodynamic activity of omadacycline against
Streptococcus pneumoniae
. Four strains with various phenotypic resistances to other antimicrobials, including tetracyclines, were utilized. Drug concentration measurements were performed in the plasma and epithelial lining fluid (ELF) after administration of 0.5, 2, 8, and 32 mg/kg. Pharmacokinetic parameters were calculated using a noncompartmental model and were linear over the dose range. Penetration into ELF ranged from 72 to 102%. Omadacycline demonstrated net cidal activity in relation to the initial burden against all four strains. The pharmacokinetic/pharmacodynamic index AUC/MIC correlated well with efficacy (
R
2
= 0.74). The plasma 24-h static dose AUC/MIC values were 16 to 20 (24-h ELF AUC/MIC of 14 to 18). A 1-log
10
kill was achieved at 24-h plasma AUC/MIC values of 6.1 to 180 (24-h ELF AUC/MIC values 6.0 to 200). A 2-log
10
kill was achieved at 24-h plasma AUC/MIC values of 19 to 56 (24-h ELF AUC/MIC of 17 to 47). The targets identified in this study in combination with
in vitro
potency and favorable human pharmacokinetics make omadacycline an attractive candidate for further development and study in patients with CABP.
qnrE1
, a Member of a New Family of Plasmid-Located Quinolone Resistance Genes, Originated from the Chromosome of Enterobacter Species
Authors: Albornoz Ezequiel , Tijet Nathalie , De Belder Denise , Gomez Sonia , Martino Florencia , Corso Alejandra , Melano Roberto G. , Petroni Alejandro 
Published: February 2017

ABSTRACT

qnrE1
, found in a clinical
Klebsiella pneumoniae
isolate, was undetectable by PCR assays used for the six
qnr
families.
qnrE1
was located on a conjugative plasmid (ca. 185 kb) and differed from
qnrB
alleles by 25%. Phylogenetic reconstructions of
qnr
genes and proteins and analysis of the
qnrE1
surroundings showed that this gene belongs to a new
qnr
family and was likely mobilized by IS
Ecp1
from the chromosome of
Enterobacter
spp. to plasmids of
K. pneumoniae
.
Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner
Authors: Yao Hua , Zhang Hong , Lan Kai , Wang Hong , Su Yufeng , Li Dagen , Song Zhixin , Cui Fang , Yin Yibing , Zhang Xuemei 
Published: February 2017

ABSTRACT

Insights into the host-microbial virulence factor interaction, especially the immune signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases.
Streptococcus pneumoniae
endopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with the isogenic wild-type strain. It is still unknown whether PepO is involved in the host defense response to pneumococcal infection. Here, we demonstrated that PepO could enhance phagocytosis of
Streptococcus pneumoniae
and
Staphylococcus aureus
by peritoneal exudate macrophages (PEMs). Further studies showed that PepO stimulation upregulated the expression of microRNA-155 (miR-155) in PEMs in a time- and dose-dependent manner. PepO-induced enhanced phagocytosis was decreased in cells transfected with an inhibitor of miR-155, while it was increased in cells transfected with a mimic of miR-155. We also revealed that PepO-induced upregulation of miR-155 in PEMs was mediated by Toll-like receptor 2 (TLR2)–NF-κB signaling and that the increased expression of miR-155 downregulated expression of SHIP1. Taken together, these results indicate that PepO induces upregulation of miR-155 in PEMs, contributing to enhanced phagocytosis and host defense response to pneumococci and
Staphylococcus aureus
.
Effector Overlap between the
lac
and
mel
Operons of Escherichia coli: Induction of the
mel
Operon with β-Galactosides
Authors: Narang Atul , Oehler Stefan 
Published: February 2017

ABSTRACT

The
lac
(lactose) operon (which processes β-galactosides) and the
mel
(melibiose) operon (which processes α-galactosides) of
Escherichia coli
have a close historical connection. A number of shared substrates and effectors of the permeases and regulatory proteins have been reported over the years. Until now, β-thiogalactosides like TMG (methyl-β-
d
-thiogalactopyranoside) and IPTG (isopropyl-β-
d
-thiogalactopyranoside) have not generally been considered to be inducers of the
mel
operon. The same is true for β-galactosides such as lactose [β-
d
-galactopyranosyl-(1→4)-
d
-glucose], which is a substrate but is not itself an inducer of the
lac
operon. This report shows that all three sugars can induce the
mel
operon significantly when they are accumulated in the cell by Lac permease. Strong induction by β-thiogalactosides is observed in the presence of Lac permease, and strong induction by lactose (more than 200-fold) is observed in the absence of β-galactosidase. This finding calls for reevaluation of TMG uptake experiments as assays for Lac permease that were performed with
mel

+

strains.

IMPORTANCE
The typical textbook picture of bacterial operons is that of stand-alone units of genetic information that perform, in a regulated manner, well-defined cellular functions. Less attention is given to the extensive interactions that can be found between operons. Well-described examples of such interactions are the effector molecules shared by the
lac
and
mel
operons. Here, we show that this set has to be extended to include β-galactosides, which have been, until now, considered not to effect the expression of the
mel
operon. That they can be inducers of the
mel
operon as well as the
lac
operon has not been noted in decades of research because of the
Escherichia coli
genetic background used in previous studies.
Assessment of Insertion Sequence Mobilization as an Adaptive Response to Oxidative Stress in Acinetobacter baumannii Using IS-seq
Authors: Wright Meredith S. , Mountain Stephanie , Beeri Karen , Adams Mark D. 
Published: February 2017

ABSTRACT

Insertion sequence (IS) elements are found throughout bacterial genomes and contribute to genome variation by interrupting genes or altering gene expression. Few of the more than 30 IS elements described in
Acinetobacter baumannii
have been characterized for transposition activity or expression effects. A targeted sequencing method, IS-seq, was developed to efficiently map the locations of new insertion events in
A. baumannii
genomes and was used to identify novel IS sites following growth in the presence of hydrogen peroxide, which causes oxidative stress. Serial subculture in the presence of subinhibitory concentrations of hydrogen peroxide led to rapid selection of cells carrying an IS
Aba1
element upstream of the catalase-peroxidase gene
katG
. Several additional sites for the elements IS
Aba1
, IS
Aba13
, IS
Aba25
, IS
Aba26
, and IS
Aba125
were found at low abundance after serial subculture, indicating that each element is active and contributes to genetic variation that may be subject to selection. Following hydrogen peroxide exposure, rapid changes in gene expression were observed in genes related to iron homeostasis. The IS insertions adjacent to
katG
resulted in more than 20-fold overexpression of the gene and increased hydrogen peroxide tolerance.

IMPORTANCE
Insertion sequences (IS) contribute to genomic and phenotypic variation in many bacterial species, but little is known about how transposition rates vary among elements or how selective pressure influences this process. A new method for identifying new insertion locations that arise under experimental growth conditions in the genome, termed IS-seq, was developed and tested with cells grown in the presence of hydrogen peroxide, which causes oxidative stress. Gene expression changes in response to hydrogen peroxide exposure are similar to those observed in other species and include genes that control free iron concentrations. New IS insertions adjacent to a gene encoding a catalase enzyme confirm that IS elements can rapidly contribute to adaptive variation in the presence of selection.
A new model for turbidity current behavior based on integration of flow monitoring and precision coring in a submarine canyon
Authors: Symons William O. , Sumner Esther J. , Paull Charles K. , Cartigny Matthieu J.B. , Xu J.P. , Maier Katherine L. , Lorenson Thomas D. , Talling Peter J. 
Published: February 2017

Abstract
Submarine turbidity currents create some of the largest sediment accumulations on Earth, yet there are few direct measurements of these flows. Instead, most of our understanding of turbidity currents results from analyzing their deposits in the sedimentary record. However, the lack of direct flow measurements means that there is considerable debate regarding how to interpret flow properties from ancient deposits. This novel study combines detailed flow monitoring with unusually precisely located cores at different heights, and multiple locations, within the Monterey submarine canyon, offshore California, USA. Dating demonstrates that the cores include the time interval that flows were monitored in the canyon, albeit individual layers cannot be tied to specific flows. There is good correlation between grain sizes collected by traps within the flow and grain sizes measured in cores from similar heights on the canyon walls. Synthesis of flow and deposit data suggests that turbidity currents sourced from the upper reaches of Monterey Canyon comprise three flow phases. Initially, a thin (38–50 m) powerful flow in the upper canyon can transport, tilt, and break the most proximal moorings and deposit chaotic sands and gravel on the canyon floor. The initially thin flow front then thickens and deposits interbedded sands and silty muds on the canyon walls as much as 62 m above the canyon floor. Finally, the flow thickens along its length, thus lofting silty mud and depositing it at greater altitudes than the previous deposits and in excess of 70 m altitude.
PREVALENCE OF ADVERSE DRUG REACTIONS AMONG HIV/AIDS PATIENTS ON HAART IN UNIVERSITY OF MAIDUGURI TEACHING HOSPITAL (UMTH), NIGERIA: A FOUR-YEAR RETROSPECTIVE STUDY
Authors: Bassi Peter , Gashau Wadzani , Olaf Klungel , Dodoo Alexander , Okonkwo Prosper , Kanki Phyllis 
Published: February 2017

BackgroundCurrent evidence on highly active antiretroviral therapy (HAART) indicates that each person will have to take the drugs for life [1]. Since 2000, the prevalence of HIV in Nigeria has shown a gradual consistent decline from 5.0% in 2003 to 4.1% in 2010 following the introduction of HAART. While HAART improves the quality of life among HIV patients, adverse drug reactions (ADRs) may compromise quality of life in some patients.MethodsWe performed a retrospective study at HIV/AIDs clinic, UMTH Nigeria, among ART-naive adult patients recruited from January 2006 to December 2010 and followed up for 48 months from commencement of HAART. Database and clinical charts of eligible patients were extracted for clinical information, type of reported ADRs, and physician's decision on whether or not ADRs was serious according to ICH E2A guidelines. Data was analysed using SPSS Ver. 21. Logistic regression was used to calculate odds ratios and of ADR associated with patient and treatment characteristics.ResultsPatients initiated on HAART (n=7260) were reviewed with a prevalence of serious ADRs (53.4%). Commonest ADRs were peripheral neuropathy (11.0%), itching (9.5%), anaemia (9.2%), dyspepsia (9.1%) skin rashes (9.1%), and various forms of dermatitis (5.5%). Almost all (96%) the reported ADRs occurred between 3–18 months of treatment. Patients initiating on a zidovudine and efavirenz-based regimen (p=0.015 and p=0.020 respectively), baseline CD4≤200/ mm3 (P=0.000), unemployed patients (P=0.000), students (p=0.000) and petty traders (p=0.000) were statistically significantly associated with increase occurrence of an ADR.ConclusionsThe study has identified the prevalence, types and the determinants of ADRs among HIV/AIDs patients at UMTH, Nigeria. These findings might be helpful in developing clinical guidelines on ADRs profile as a major criterion for choosing HAART drugs, hence promoting pharmacovigilance of ARVs in Nigeria.
STRENGTHENING PRISON HEALTH SYSTEMS: FEASIBILITY AND CHALLENGES OF INTRODUCING PRISON HEALTH COMMITTEES (PRHCS) IN ZAMBIAN CORRECTIONAL FACILITIES
Authors: Moonga Clement , Chileshe Chisele , Magwende George , Henostroza German , Topp Stephanie 
Published: February 2017

BackgroundIn Zambia, prison health and health services are in a state of ‘chronic emergency’. Since 2013, the Zambian Corrections Service (ZCS) partnered with Centre for Infectious Disease Research in Zambia (CIDRZ) to understand and strengthen prisoner health and access to healthcare. A key component of this work was the establishment of 11 facility-level Prison Healthcare Committees (PrHCs) comprising officer and inmate members, with a specific remit to deliver health education and provide monitoring for facility level service access. Findings presented are from operations research evaluating the feasibility of these PrHCs.MethodsMixed qualitative methods included, in-depth interviews (11 Ministry and ZCS officials; 6 facility managers) and focus group discussions (FGDs) with members of 6 PrHCs, and 6 groups of non-PrHC-inmates in the same facilities. Memos were generated from participant observation in workshops and meetings preceding and after implementation. All activities were subject to verbal informed consent and interviews and FGDs were audio-recorded with permission.ResultsKey informants were strongly supportive of PrHCs, noting potential for improved health information dissemination, strengthened preventive service-coverage, routine service monitoring and facility-level accountability. PrHC members confirmed ZCS-led training had taken place and that they had been given authority to deliver information-based health interventions and facilitate quicker referrals to primary care. The early phase of implementation (3–6 months at data collection) produced mixed accounts regarding PrHCs' capacity to fulfil other preventive services or conduct data collection. Departure of PrHC members due to transfer and/or release was the most frequently listed challenge.ConclusionsThese data suggest the feasibility of establishing a committee comprising both officers and inmates to address a fundamental gap in facility-level mechanisms for health information delivery and service accountability. Findings nonetheless suggest PrHCs will require iterative adjustments and ongoing problem-solving by local officials. Context-sensitive application of these principles to other settings may yield positive outcomes.
Are parents’ motivations to exercise and intention to engage in regular family-based activity associated with both adult and child physical activity?
Authors: Solomon-Moore Emma , Sebire Simon J , Thompson Janice L , Zahra Jesmond , Lawlor Debbie A , Jago Russ 
Published: February 2017

Background/aimTo examine the associations between parents’ motivation to exercise and intention to engage in family-based activity with their own and their child’s physical activity.MethodsCross-sectional data from 1067 parent–child pairs (76.1% mother–child); children were aged 5–6 years. Parents reported their exercise motivation (ie, intrinsic motivation, identified regulation, introjected regulation, external regulation and amotivation) as described in self-determination theory and their intention to engage in family-based activity. Parents’ and children’s mean minutes of moderate-to-vigorous-intensity physical activity (MVPA) and mean counts per minute were derived from ActiGraph accelerometers worn for 3 to 5 days (including a mixture of weekdays and weekend days). Multivariable linear regression models, adjusted for parent sex, number of children, indices of multiple deprivation and clustering of children in schools were used to examine associations (total of 24 associations tested).ResultsIn fully adjusted models, each unit increase in identified regulation was associated with a 6.08 (95% CI 3.27 to 8.89, p<0.001) min-per-day increase in parents’ MVPA. Parents’ external regulation was associated with children performing 2.93 (95% CI −5.83 to −0.03, p=0.05) fewer minutes of MVPA per day and a 29.3 (95% CI −53.8 to −4.7, p=0.02) accelerometer count-per-minute reduction. There was no evidence of association for the other 21 associations tested.ConclusionsFuture family-based physical activity interventions may benefit from helping parents identify personal value in exercise while avoiding the use of external control or coercion to motivate behaviour.