bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton Pump Inhibitors and Functional Decline in Older Adults Discharged From Acute Care Hospitals
Authors: Corsonello Andrea , Maggio Marcello , Fusco Sergio , Adamo Bakhita , Amantea Diana , Pedone Claudio , Garasto Sabrina , Ceda Gian Paolo , Corica Francesco , Lattanzio Fabrizia , Antonelli Incalzi Raffaele 
Published: May 2014

ObjectivesTo investigate the relationship between use of proton pump inhibitors (PPIs) and incident dependency in older adults discharged from acute care hospitals.DesignProspective observational study.SettingEleven geriatric and internal medicine acute care wards located throughout Italy.ParticipantsIndividuals (mean age 79.2 ± 5.5) who were not completely dependent at the time of discharge from participating wards (N = 401).MeasurementsThe outcome of interest was the loss of at least one basic activity of daily living (ADL) from discharge to the end of follow‐up (12 months). The relationship between PPI use and functional decline was investigated using logistic regression analysis before and after propensity score matching.ResultsUse of PPIs was significantly associated with functional decline before (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.17–2.60) and after propensity score matching (OR = 2.44; 95% CI = 1.36–4.41). Other predictors of functional decline were hypoalbuminemia (OR = 3.10, 95% CI = 1.36–7.10 before matching, OR = 2.81, 95% CI = 1.09–7.77 after matching) and cognitive impairment (OR = 4.08, 95% CI = 1.63–10.2 before matching, OR = 6.35, 95% CI = 1.70–24.0 after matching).ConclusionUse of PPIs is associated with functional decline during 12 months of follow‐up in older adults discharged from acute care hospitals.
Quality of End‐of‐Life Care Among Rural Medicare Beneficiaries With Colorectal Cancer
Authors: Watanabe‐Galloway Shinobu , Zhang Wanqing , Watkins Kate , Islam KM , Nayar Preethy , Boilesen Eugene , Lander Lina , Wang Hongmei , Qiu Fang 
Published: May 2014

AbstractBackgroundAlthough previous research has documented rural disparities in hospice use, limited data exist on the roles of geographic access in different types of end‐of‐life indicators among cancer survivors.MethodsMedicare claims data were used to identify beneficiaries with colorectal cancer who died in 2008 (N = 34,975). We evaluated rural‐urban differences in ER visits 90 days before death, inpatient hospital admissions ≤90 days before death, intensive care unit (ICU) use ≤90 days before death, hospice care use at any time, and hospice enrollment <3 days before death.ResultsAbout 60% of beneficiaries in rural areas lived in counties with the 2 lowest socioecomonic levels compared to only 5.3% of beneficiaries in metropolitan areas. After adjusting for demographic factors and comorbidities, beneficiaries in rural counties had a lower number of ICU days (RR = 0.65) and were less likely to ever use hospice (OR = 0.78) compared to those in metropolitan counties. Beneficiaries from racial/ethnic minority groups, those with lower socioeconomic status, and those with a higher comorbidity index were less likely to ever use hospice but they tended to use ER, inpatient care, and ICU.ConclusionsEvidence for disparities due to geographic access and socioeconomic factors warrant increased efforts to remove systemic and structural barriers. Future research should focus on exploring and evaluating potential policy and practice interventions to improve the quality of life among elderly cancer survivors living in rural communities and those from socioeconomically disadvantaged backgrounds.
Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of portopulmonary hypertension
Authors: Chiva Teresa , Ripoll Cristina , Sarnago Fernando , Rincón Diego , Gómez‐Camarero Judith , Galindo Evelyn , Catalina María‐Vega , Elizaga Jaime , Bañares Rafael 
Published: May 2014

AbstractBackground & AimsDiagnosis of portopulmonary hypertension (POPH) is based on the presence of portal hypertension and the same haemodynamic criteria as pulmonary arterial hypertension (PAH). However, the typical hyperdynamic circulation of cirrhosis may have some impact on the diagnosis of POPH. The aim was to compare the haemodynamic pattern of the pulmonary circulation between cirrhotics and non‐cirrhotics, including patients with PAH.Patients and Methods600 patients with cirrhosis [male 77.5%, age 54 (47–60) years, Child A: 14.7%, B: 54.3%, C: 31%] received right heart catheterization. For comparison, 118 non‐cirrhotic patients [male 60%, age 64 (53–65) years] with right heart catheterization and PCWP <20 mmHg were included. Both were divided into 3 groups, A: absence of pulmonary arterial hypertension; B or intermediate group: MPAP >25 mmHg, PVR 120–240 dyn s cm−5 and PCWP <15 mmHg (or PCWP >15 mmHg with TPG ≥12 mmHg); C: pulmonary arterial hypertension (same criteria as B except PVR ≥240 dyn s cm−5).ResultsDistribution of patients with cirrhosis was A 583, B 7 and C 10. Prevalence of POPH was 1.7%. Cirrhotics had lower SVR and greater CO than non‐cirrhotics (P < 0.05). Interestingly, patients with cirrhosis without PAH (groups A and B) had lower PVR (P < 0.05) when comparing with non‐cirrhotics, while no differences in PVR were observed in group C. However, mean TPG was greater in group C of cirrhotics [36.6 mmHg (12.2) vs. 27.1 mmHg (10.1); P = 0.034].ConclusionsPatients with cirrhosis have lower PVR. TPG is greater in POPH than PAH. Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of POPH.
Use and reimbursement of off‐label drugs in pediatric anesthesia: the Italian experience
Authors: Salvo Ida , Landoni Giovanni , Mucchetti Marta , Cabrini Luca , Pani Luca 
Published: May 2014

SummaryBackgroundMost of the drugs used in anesthesia are off‐label in children even if they present solid clinical evidence in adults. This lack of authorization is caused by multiple factors including the difficulty in conducting research in this area (due to the ethical concerns and/or the low number of available participants, the high variability of the outcome measures) and the lack of economic interest of the pharmaceutical companies (due to the limited market).ObjectiveDefine a list of medicinal products commonly used off‐label in pediatrics anesthesia to be reimbursed by Italian National Health System.Methods and resultsWe hereby describe the methodological framework used to allow reimbursed use of a list of medicinal products, widely used off‐label in pediatric patients, ensuring the best therapeutic results with the lowest possible risk for children. A task force of pediatric anesthesiologists from Italy petitioned the Italian Medicines Agency (AIFA) to allow a number of commonly utilized but off‐label drugs for pediatric anesthesia to be reimbursed for specific indications. For each drug, both the supporting literature and expert opinion were used, and the resulting list of drugs allowed to be used/reimbursed officially by AIFA was significantly expanded. This paper documents one approach to the problem of off‐label use of drugs for pediatric patients that can be a model for future efforts.ConclusionContinuous efforts are needed from government institutions and sponsors on drug development and on drug approval process in pediatrics, as research on drug effectiveness and safety is mandatory in children as in adults. At the same time, clinicians must become more familiar with the drug‐approval process, participate to sponsored trials, and perform ztrials themselves.
Garment Industry in Sri Lanka and the Removal of GSP Plus by EU
Authors: Bandara Jayatilleke S. , Naranpanawa Athula 
Published: May 2014

AbstractThe ready‐made garment industry plays an important role in Sri Lanka both in terms of export earnings and poverty alleviation through employment generation. Following the removal of GSP Plus by EU in 2010 on the basis of alleged human right violations by the Sri Lankan government during the last stage of the civil war in 2009 and after, it currently faces serious challenges in exporting to the EU, its major market. Given the important role of the ready‐made garment industry in poverty alleviation through employment generation, the impact of removal of GSP plus on the poor is examined in this paper. The empirical results of this study demonstrate that poverty and income inequality are expected to be exacerbated in Sri Lanka as a result of the removal of GSP Plus by the EU using non‐economic reasons such as human rights violation. The results are also relevant for the renewed emphasis on trade preferences as a potential instrument for the Millennium Development Goals and the debate on how trade preferences are to be designed to maximise their effectiveness in stimulating a manufacturing supply response.
On the Stability of Fractional-Order Systems of Neutral Type
Authors: Pakzad Mohammad Ali , Pakzad Sara , Nekoui Mohammad Ali 
Published: May 2014

AbstractThe aim of this study is to offer a new analytical method for the stability testing of neutral type linear time-invariant (LTI) time-delayed fractional-order systems with commensurate orders and multiple commensurate delays. It is evident from the literature that the stability assessment of this class of dynamics remains unsolved yet and this is the first attempt to take up this challenging problem. The method starts with the determination of all possible purely imaginary characteristic roots for any positive time delay. To achieve this, the Rekasius transformation is used for the transcendental terms in the characteristic equation. An explicit analytical expression in terms of the system parameters which reveals the stability regions (pockets) in the domain of time delay has been presented. The number of unstable roots in each delay interval is calculated with the definition of root tendency (RT) on the boundary of each interval. Two example case studies are also provided, which are not possible to analyze using any other methodology known to the authors.
Individualization of Piperacillin Dosing for Critically Ill Patients: Dosing Software To Optimize Antimicrobial Therapy
Authors: Felton T. W. , Roberts J. A. , Lodise T. P. , Van Guilder M. , Boselli E. , Neely M. N. , Hope W. W. 
Published: May 2014

ABSTRACT

Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an
r
2
of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.
Involvement of the Global Regulator GlxR in 3-Hydroxybenzoate and Gentisate Utilization by Corynebacterium glutamicum
Authors: Chao Hongjun , Zhou Ning-Yi 
Published: May 2014

ABSTRACT

Corynebacterium glutamicum
is an industrially important producer of amino acids and organic acids, as well as an emerging model system for aromatic assimilation. An IclR-type regulator GenR has been characterized to activate the transcription of
genDFM
and
genKH
operons for 3-hydroxybenzoate and gentisate catabolism and represses its own expression. On the other hand, GlxR, a global regulator of the cyclic AMP (cAMP) receptor protein-fumarate nitrate reductase regulator (CRP-FNR) type, was also predicted to be involved in this pathway. In this study, electrophoretic mobility shift assays and footprinting analyses demonstrated that GlxR bound to three sites in the promoter regions of three
gen
operons. A combination of site-directed mutagenesis of the biding sites, promoter activity assay, and GlxR overexpression demonstrated that GlxR repressed their expression by binding these sites. One GlxR binding site (DFMx) was found to be located −13 to +8 bp upstream of the
genDFM
promoter, which was involved in negative regulation of
genDFM
transcription. The GlxR binding site R-KHx01 (located between positions −11 to +5) was upstream of the
genKH
promoter sequence and involved in negative regulation of its transcription. The binding site R-KHx02, at which GlxR binds to
genR
promoter to repress its expression, was found within a footprint extending from positions −71 to −91 bp. These results reveal that GlxR represses the transcription of all three
gen
operons and then contributes to the synchronization of their expression for 3-hydroxybenzoate and gentisate catabolism in collaboration with the specific regulator GenR.
The Transcriptional Response of Lactobacillus sanfranciscensis DSM 20451
T
and Its
tcyB
Mutant Lacking a Functional Cystine Transporter to Diamide Stress
Authors: Stetina Mandy , Behr Jürgen , Vogel Rudi F. 
Published: May 2014

ABSTRACT

As a result of its strong adaptation to wheat and rye sourdoughs,
Lactobacillus sanfranciscensis
has the smallest genome within the genus
Lactobacillus
. The concomitant absence of some important antioxidative enzymes and the inability to synthesize glutathione suggest a role of cystine transport in maintenance of an intracellular thiol balance. Diamide [synonym 1,1′-azobis(
N
,
N
-dimethylformamide)] disturbs intracellular and membrane thiol levels in oxidizing protein thiols depending on its initial concentration. In this study, RNA sequencing was used to reveal the transcriptional response of
L. sanfranciscensis
DSM 20451
T
(wild type [WT]) and its Δ
tcyB
mutant with a nonfunctional cystine transporter after thiol stress caused by diamide. Along with the different expression of genes involved in amino acid starvation, pyrimidine synthesis, and energy production, our results show that thiol stress in the wild type can be compensated through activation of diverse chaperones and proteases whereas the Δ
tcyB
mutant shifts its metabolism in the direction of survival. Only a small set of genes are significantly differentially expressed between the wild type and the mutant. In the WT, mainly genes which are associated with a heat shock response are upregulated whereas glutamine import and synthesis genes are downregulated. In the Δ
tcyB
mutant, the whole
opp
operon was more highly expressed, as well as a protein which probably includes enzymes for methionine transport. The two proteins encoded by
spxA
and
nrdH
, which are involved in direct or indirect oxidative stress responses, are also upregulated in the mutant. This work emphasizes that even in the absence of definitive antioxidative enzymes, bacteria with a small genome and a high frequency of gene inactivation and elimination use small molecules such as the cysteine/cystine couple to overcome potential cell damage resulting from oxidative stress.
Discovery of Ethanol-Responsive Small RNAs in Zymomonas mobilis
Authors: Cho Seung Hee , Lei Roy , Henninger Trey D. , Contreras Lydia M. 
Published: May 2014

ABSTRACT

Zymomonas mobilis
is a bacterium that can produce ethanol by fermentation. Due to its unique metabolism and efficient ethanol production,
Z. mobilis
has attracted special interest for biofuel energy applications; an important area of study is the regulation of those specific metabolic pathways. Small RNAs (sRNAs) have been studied as molecules that function as transcriptional regulators in response to cellular stresses. While sRNAs have been discovered in various organisms by computational prediction and experimental approaches, their discovery in
Z. mobilis
has not yet been reported. In this study, we have applied transcriptome analysis and computational predictions to facilitate identification and validation of 15 novel sRNAs in
Z. mobilis
. We furthermore characterized their expression in the context of high and low levels of intracellular ethanol. Here, we report that 3 of the sRNAs (Zms2, Zms4, and Zms6) are differentially expressed under aerobic and anaerobic conditions, when low and high ethanol productions are observed, respectively. Importantly, when we tested the effect of ethanol stress on the expression of sRNAs in
Z. mobilis
, Zms2, Zms6, and Zms18 showed differential expression under 5% ethanol stress conditions. These data suggest that in this organism regulatory RNAs can be associated with metabolic functions involved in ethanol stress responses.
Functional Genomic Characterization of Virulence Factors from Necrotizing Fasciitis-Causing Strains of Aeromonas hydrophila
Authors: Grim Christopher J. , Kozlova Elena V. , Ponnusamy Duraisamy , Fitts Eric C. , Sha Jian , Kirtley Michelle L. , van Lier Christina J. , Tiner Bethany L. , Erova Tatiana E. , Joseph Sandeep J. , Read Timothy D. , Shak Joshua R. , Joseph Sam W. , Singletary Ed , Felland Tracy , Baze Wallace B. , Horneman Amy J. , Chopra Ashok K. 
Published: May 2014

ABSTRACT

The genomes of 10
Aeromonas
isolates identified and designated
Aeromonas hydrophila
WI, Riv3, and NF1 to NF4;
A. dhakensis
SSU;
A. jandaei
Riv2; and
A. caviae
NM22 and NM33 were sequenced and annotated. Isolates NF1 to NF4 were from a patient with necrotizing fasciitis (NF). Two environmental isolates (Riv2 and -3) were from the river water from which the NF patient acquired the infection. While isolates NF2 to NF4 were clonal, NF1 was genetically distinct. Outside the conserved core genomes of these 10 isolates, several unique genomic features were identified. The most virulent strains possessed one of the following four virulence factors or a combination of them: cytotoxic enterotoxin, exotoxin A, and type 3 and 6 secretion system effectors AexU and Hcp. In a septicemic-mouse model, SSU, NF1, and Riv2 were the most virulent, while NF2 was moderately virulent. These data correlated with high motility and biofilm formation by the former three isolates. Conversely, in a mouse model of intramuscular infection, NF2 was much more virulent than NF1. Isolates NF2, SSU, and Riv2 disseminated in high numbers from the muscular tissue to the visceral organs of mice, while NF1 reached the liver and spleen in relatively lower numbers on the basis of colony counting and tracking of bioluminescent strains in real time by
in vivo
imaging. Histopathologically, degeneration of myofibers with significant infiltration of polymorphonuclear cells due to the highly virulent strains was noted. Functional genomic analysis provided data that allowed us to correlate the highly infectious nature of
Aeromonas
pathotypes belonging to several different species with virulence signatures and their potential ability to cause NF.
Mannosylglycerate and Di-
myo
-Inositol Phosphate Have Interchangeable Roles during Adaptation of Pyrococcus furiosus to Heat Stress
Authors: Esteves Ana M. , Chandrayan Sanjeev K. , McTernan Patrick M. , Borges Nuno , Adams Michael W. W. , Santos Helena 
Published: May 2014

ABSTRACT

Marine hyperthermophiles accumulate small organic compounds, known as compatible solutes, in response to supraoptimal temperatures or salinities.
Pyrococcus furiosus
is a hyperthermophilic archaeon that grows optimally at temperatures near 100°C. This organism accumulates mannosylglycerate (MG) and di-
myo
-inositol phosphate (DIP) in response to osmotic and heat stress, respectively. It has been assumed that MG and DIP are involved in cell protection; however, firm evidence for the roles of these solutes in stress adaptation is still missing, largely due to the lack of genetic tools to produce suitable mutants of hyperthermophiles. Recently, such tools were developed for
P. furiosus
, making this organism an ideal target for that purpose. In this work, genes coding for the synthases in the biosynthetic pathways of MG and DIP were deleted by double-crossover homologous recombination. The growth profiles and solute patterns of the two mutants and the parent strain were investigated under optimal growth conditions and also at supraoptimal temperatures and NaCl concentrations. DIP was a suitable replacement for MG during heat stress, but substitution of MG for DIP and aspartate led to less efficient growth under conditions of osmotic stress. The results suggest that the cascade of molecular events leading to MG synthesis is tuned for osmotic adjustment, while the machinery for induction of DIP synthesis responds to either stress agent. MG protects cells against heat as effectively as DIP, despite the finding that the amount of DIP consistently increases in response to heat stress in the nine (hyper)thermophiles examined thus far.
Targeted and Highly Multiplexed Detection of Microorganisms by Employing an Ensemble of Molecular Probes
Authors: Xu Weihong , Krishnakumar Sujatha , Miranda Molly , Jensen Michael A. , Fukushima Marilyn , Palm Curtis , Fung Eula , Davis Ronald W. , St.Onge Robert P. , Hyman Richard W. 
Published: May 2014

ABSTRACT
The vast majority of microscopic life on earth consists of microbes that do not grow in laboratory culture. To profile the microbial diversity in environmental and clinical samples, we have devised and employed molecular probe technology, which detects and identifies bacteria that do and do not grow in culture. The only requirement is a short sequence of contiguous bases (currently 60 bases) unique to the genome of the organism of interest. The procedure is relatively fast, inexpensive, customizable, robust, and culture independent and uses commercially available reagents and instruments. In this communication, we report improving the specificity of the molecular probes substantially and increasing the complexity of the molecular probe set by over an order of magnitude (>1,200 probes) and introduce a new final readout method based upon Illumina sequencing. In addition, we employed molecular probes to identify the bacteria from vaginal swabs and demonstrate how a deliberate selection of molecular probes can identify less abundant bacteria even in the presence of much more abundant species.