bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes in Acute Ischemic Strokes Presenting with Disabling Neurologic Deficits without Intracranial Vascular Occlusion
Authors: Shobha Nandavar , Bhatia Rohit , Boyko Matthew , Tymchuk Sarah , Kumarpillai Gopukumar , Smith Eric , Demchuk Andrew M. 
Published: June 2011

Background Patients with moderate to severe acute ischemic stroke without intracranial vessel occlusion are an intriguing subset of stroke patients. They pose diagnostic and therapeutic challenges to the physician. We sought to study these patients with an emphasis on their radiological and clinical outcomes. Methods This is a retrospective cohort study of ischemic stroke patients (NIHSS ≥ 6), with no intracranial vessel occlusion on computed tomography angiography within six-hours of symptom onset. Follow-up imaging – either computed tomography brain or magnetic resonance imaging – was performed within one- to seven-days. The primary outcome was modified Rankin Scale score ≤ 2 at three-months. Results In a database of 1308 patients, we identified 99 (7·6%) patients with NIHSS≥6 and no intracranial vessel occlusion on computed tomography angiography. The mean age was 67·8 ± 15·4 years and 60 (60·6%) were men. The median baseline NIHSS was nine (6–28). The initial computed tomography head was normal in 79 (79·8%) patients. Dramatic early clinical improvement at 24 h (NIHSS score ≤2 at 24 h or change between baseline and 24 h NIHSS score 15 points) was seen in 38 (38·4%) patients. Follow-up scans showed infarcts in 66 (66·7%) patients. Fifty (50·5%) patients received tissue plasminogen activator; one (2%) tissue plasminogen activator-treated patient developed symptomatic intracranial hemorrhage. At three-months; 59 (59·6%) patients were independent (modified Rankin Scale ≤2), 34 (34·3%) patients were dependent (modified Rankin Scale 3–5), and six (6·1%) were dead. The factors associated with the unlikelihood of good outcome were higher initial NIHSS (odds ratio 0·86 per additional point, 95% confidence interval 0·77–0·95, P = 0·003), and older age (odds ratio 0·95 per additional year, 95% confidence interval 0·92–0·98, P = 0·004). Conclusion Stroke without intracranial occlusions are not a benign entity. Factors that are independently associated with decreased likelihood of a good outcome are higher baseline NIHSS, and older age. Treatment with tissue plasminogen activator is not a predictor of outcome.
Red Cell Distribution Width Does Not Predict Stroke Severity or Functional Outcome
Authors: Ntaios George , Gurer Ozgur , Faouzi Mohamed , Aubert Carole , Michel Patrik 
Published: June 2011

Introduction Red cell distribution width was recently identified as a predictor of cardiovascular and all-cause mortality in patients with previous stroke. Red cell distribution width is also higher in patients with stroke compared with those without. However, there are no data on the association of red cell distribution width, assessed during the acute phase of ischemic stroke, with stroke severity and functional outcome. In the present study, we sought to investigate this relationship and ascertain the main determinants of red cell distribution width in this population. Methods We used data from the Acute Stroke Registry and Analysis of Lausanne for patients between January 2003 and December 2008. Red cell distribution width was generated at admission by the Sysmex XE-2100 automated cell counter from ethylene diamine tetraacetic acid blood samples stored at room temperature until measurement. An χ2-test was performed to compare frequencies of categorical variables between different red cell distribution width quartiles, and one-way analysis of variance for continuous variables. The effect of red cell distribution width on severity and functional outcome was investigated in univariate and multivariate robust regression analysis. Level of significance was set at 95%. Results There were 1504 patients (72±15·76 years, 43·9% females) included in the analysis. Red cell distribution width was significantly associated to NIHSS ( β-value=0·24, P=0·01) and functional outcome (odds ratio=10·73 for poor outcome, P<0·001) at univariate analysis but not multivariate. Prehospital Rankin score ( β=0·19, P<0·001), serum creatinine ( β=0·008, P<0·001), hemoglobin ( β=−0·009, P<0·001), mean platelet volume ( β=0·09, P<0·05), age ( β=0·02, P<0·001), low ejection fraction ( β=0·66, P<0·001) and antihypertensive treatment ( β=0·32, P<0·001) were independent determinants of red cell distribution width. Conclusions Red cell distribution width, assessed during the early phase of acute ischemic stroke, does not predict severity or functional outcome.
Calculation of Numbers-Needed-To-Treat in Parallel Group Trials Assessing Ordinal Outcomes: Case Examples from Acute Stroke and Stroke Prevention
Authors: Bath Philip , Hogg Cheryl , Tracy Michael , Pocock Stuart 
Published: June 2011

Background Number-needed-to-treat describes the magnitude of the effect of an intervention, underpins health economic analyses, and is typically calculated for binary events. Ordered categorical outcomes provide more clinical information and their analysis using ordinal approaches is usually more efficient statistically. However, to date, techniques to calculate number-needed-to-treat based on ordinal outcomes for parallel group trials have had important limitations. Aims Numbers-needed-to-treat may be calculated for ordinal data from parallel group trials by using an unmatched comparison of all subjects or by generating matched pairs of patients nested within the study. Methods The above approaches were assessed and compared with numbers-needed-to-treat calculated for binary outcomes using individual patient data from acute and prevention stroke trials testing the effect of interventions of varying utility and efficacy. Results Numbers-needed-to-treat were generally lower numerically for ordinal vs. binary, and matched vs. unmatched analyses, and the lowest in highly efficacious interventions: hemicraniectomy, ordinal matched 2·4 vs. ordinal unmatched 2·5 vs. binary matched 12 vs. binary unmatched 9 (one trial, 12 month outcome); alteplase, 4·5 vs. 6·6 vs. 8·4 vs. 8·4 (one trial with two parts, three-months); aspirin, 42 vs. 58 vs. 76 vs. 80 (one trial, six-months); and stroke units, 3·6–5·3 vs. 6·2 vs. 4·7–5·9 vs. 6·3–7·0 (two trials, three- to 60 months). Similar trends were seen for aspirin/dipyridamole vs. aspirin in secondary prevention, 22 vs. 20 vs. 31 vs. 31 (one trial, 24 months). Conclusions Number-needed-to-treat may be calculated for ordinal outcome data derived from parallel group stroke trials; such numbers-needed-to-treat are lower than those calculated for binary outcomes. Their use complements the use of ordinal statistical approaches in the analysis of ordered categorical data.
Aims and Results of the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD)
Authors: Bowden C.L. , Perlis R.H. , Thase M.E. , Ketter T.A. , Ostacher M.M. , Calabrese J.R. , Reilly‐Harrington N.A. , Gonzalez J.M. , Singh V. , Nierenberg A.A. , Sachs G.S. 
Published: June 2011

SUMMARYThe Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP‐BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP‐BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP‐BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP‐BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders.
Antiplasmodial Properties of Acyl-Lysyl Oligomers in Culture and Animal Models of Malaria
Authors: Zaknoon Fadia , Wein Sharon , Krugliak Miriam , Meir Ohad , Rotem Shahar , Ginsburg Hagai , Vial Henri , Mor Amram 
Published: June 2011

ABSTRACT

Our previous analysis of antiplasmodial properties exhibited by dodecanoyl-based oligo-acyl-lysyls (OAKs) has outlined basic attributes implicated in potent inhibition of parasite growth and underlined the critical role of excess hydrophobicity in hemotoxicity. To dissociate hemolysis from antiplasmodial effect, we screened >50 OAKs for
in vitro
growth inhibition of
Plasmodium falciparum
strains, thus revealing the minimal requirements for antiplasmodial potency in terms of sequence and composition, as confirmed by efficacy studies
in vivo
. The most active sequence, dodecanoyllysyl-bis(aminooctanoyllysyl)-amide (C
12
K-2α
8
), inhibited parasite growth at submicromolar concentrations (50% inhibitory concentration [IC
50
], 0.3 ± 0.1 μM) and was devoid of hemolytic activity (<0.4% hemolysis at 150 μM). Unlike the case of dodecanoyl-based analogs, which equally affect ring and trophozoite stages of the parasite developmental cycle, the ability of various octanoyl-based OAKs to distinctively affect these stages (rings were 4- to 5-fold more sensitive) suggests a distinct antiplasmodial mechanism, nonmembranolytic to host red blood cells (RBCs). Upon intraperitoneal administration to mice, C
12
K-2α
8
demonstrated sustainable high concentrations in blood (e.g., 0.1 mM at 25 mg/kg of body weight). In
Plasmodium vinckei
-infected mice, C
12
K-2α
8
significantly affected parasite growth (50% effective dose [ED
50
], 22 mg/kg) but also caused mortality in 2/3 mice at high doses (50 mg/kg/day × 4).
The Expression Levels of Outer Membrane Proteins STM1530 and OmpD, Which Are Influenced by the CpxAR and BaeSR Two-Component Systems, Play Important Roles in the Ceftriaxone Resistance of
Salmonella enterica
Serovar Typhimurium
Authors: Hu Wensi S. , Chen Hung-Wen , Zhang Rui-Yang , Huang Chung-Yi , Shen Chi-Fan 
Published: June 2011

ABSTRACT

Significant increases in STM3031, STM1530, and AcrD protein levels and significant decreases in OmpC and OmpD protein levels are present when the ceftriaxone-resistant
Salmonella enterica
serovar Typhimurium R200 strain is compared with the ceftriaxone-susceptible strain 01-4. AcrD is known to be involved in drug export, and STM3031 seems to play a key role in ceftriaxone resistance. Here, we examine the roles of STM1530, OmpC, and OmpD in ceftriaxone resistance. An
ompD
gene deletion mutant showed 4-fold higher ceftriaxone resistance than 01-4. An
ompC
gene deletion mutant showed 4-fold higher cephalothin and erythromycin resistance than 01-4, but there was no effect on ceftriaxone resistance. However, a
stm1530
deletion mutant did show >64-fold lower ceftriaxone resistance than R200. Moreover, the STM3031 protein was significantly decreased in R200(Δ
stm1530
) compared to R200. STM3031 expression has been shown to be influenced by the two-component system regulator gene
baeR
. CpxR seems to modulate BaeR. A
cpxA-cpxR
gene deletion mutant showed >2,048-fold lower ceftriaxone resistance than R200. The outer membrane protein profile of R200(Δ
cpxAR
) showed significant decreases in STM3031 and STM1530 compared to R200, while OmpD had returned to the level found in 01-4. Furthermore, the
stm3031
,
stm1530
, and
ompD
mRNA levels were correlated with their protein expression levels in these strains, while decreases in the mRNA levels of the efflux pump
acrB
,
acrD
, and
acrF
genes were found in R200(Δ
cpxAR
). Findings similar to those for R200(Δ
cpxAR
) were found for R200(Δ
baeSR
). These results, together with those for STM3031 and the fact that STM1530 is an outer membrane protein, suggest that STM1530 and OmpD are influenced by the CpxAR and BaeSR two-component systems and that this contributes to
S. enterica
serovar Typhimurium ceftriaxone resistance.
Emergence of NDM-1 Metallo-β-Lactamase in
Pseudomonas aeruginosa
Clinical Isolates from Serbia
Authors: Jovcic Branko , Lepsanovic Zorica , Suljagic Vesna , Rackov Gorjana , Begovic Jelena , Topisirovic Ljubisa , Kojic Milan 
Published: June 2011

ABSTRACT

This work reports, for the first time, the presence of New Delhi metallo-β-lactamase 1 (NDM-1) in
Pseudomonas aeruginosa
. Moreover, this is the first report of the NDM-1 presence in the Balkan region. Cosmid gene libraries of carbapenem-nonsusceptible
Pseudomonas aeruginosa
clinical isolates MMA83 and MMA533 were screened for the presence of metallo-β-lactamases. Accordingly, both MMA83 and MMA533 carried the
bla
NDM-1
gene. Pulsed-field gel electrophoresis (PFGE) analysis indicated that strains MMA83 and MMA533 belonged to different clonal groups. Five additional isolates from different patients clonally related to either MMA83 or MMA533 were found to be NDM-1 positive.
Effect of Ciprofloxacin Concentration on the Frequency and Nature of Resistant Mutants Selected from
Pseudomonas aeruginosa mutS
and
mutT
Hypermutators
Authors: Morero Natalia R. , Monti Mariela R. , Argaraña Carlos E. 
Published: June 2011

ABSTRACT

The rapid emergence of drug resistance upon treatment of
Pseudomonas aeruginosa
infections with fluoroquinolones is a serious concern. In this study, we report the effect of hypermutability on the mutant selection window for ciprofloxacin (CIP) by comparing the hypermutator MPAO1
mutS
and
mutT
strains with the wild-type strain. The mutant selection window was shifted to higher CIP concentrations for both hypermutators, presenting the
mutS
strain with a broader selection window in comparison to the wild-type strain. The mutation prevention concentrations (MPC) determined for
mutT
and
mutS
strains were increased 2- and 4-fold over the wild-type level, respectively. In addition, we analyzed the molecular bases for resistance in the bacterial subpopulations selected at different points in the window. At the top of the window, the resistant clones isolated were mainly mutated in GyrA and ParC topoisomerase subunits, while at the bottom of the window, resistance was associated with the overexpression of MexCD-OprJ and MexAB-OprM efflux pumps. Accordingly, a greater proportion of multidrug-resistant clones were found among the subpopulations isolated at the lower CIP concentrations. Furthermore, we found that the exposure to CIP subinhibitory concentrations favors the accumulation of cells overexpressing MexCD-OprJ (due to mutations in the transcriptional repressor NfxB) and MexAB-OprM efflux pumps. We discuss these results in the context of the possible participation of this antibiotic in a mutagenic process.
Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid
Authors: Leduc Isabelle , Fusco William G. , Choudhary Neelima , Routh Patty A. , Cholon Deborah M. , Hobbs Marcia M. , Almond Glen W. , Orndorff Paul E. , Elkins Christopher 
Published: June 2011

ABSTRACT

Haemophilus ducreyi
, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by
H. ducreyi
from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of
H. ducreyi
, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of
H. ducreyi
and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an
H. ducreyi
infection, possibly by preventing acquisition of the essential nutrient heme.
Serine Proteases Degrade Airway Mucins in Cystic Fibrosis
Authors: Henke Markus O. , John Gerrit , Rheineck Christina , Chillappagari Shashi , Naehrlich Lutz , Rubin Bruce K. 
Published: June 2011

ABSTRACT

Airway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronic
Pseudomonas aeruginosa
infection. In sputum from CF subjects without a history of
P. aeruginosa
, we found no significant difference in the mucin concentration compared to mucus from normal controls. We demonstrate that mucins can be degraded by synthetic human neutrophil elastase (HNE) and
P. aeruginosa
elastase B (pseudolysin) and that degradation was inhibited by serine proteases inhibitors (diisopropyl fluorophosphates [DFP], phenylmethylsulfonyl fluoride [PMSF], and 1-chloro-3-tosylamido-7-amino-2-heptanone HCl [TLCK]). The mucin concentration in airway secretions from CF subjects is similar to that for normal subjects until there is infection by
P. aeruginosa
, and after that, the mucin concentration decreases dramatically. This is most likely due to degradation by serine proteases. The loss of this mucin barrier may contribute to chronic airway infection in the CF airway.
Activation of Adenosine A2AReceptors Inhibits Neutrophil Transuroepithelial Migration
Authors: Säve Susanne , Mohlin Camilla , Vumma Ravi , Persson Katarina 
Published: June 2011

ABSTRACTAdenosine has been identified as a significant inhibitor of inflammation by acting on adenosine A2Areceptors. In this study, we examined the role of adenosine and A2Areceptors in the transmigration of human neutrophils across anin vitromodel of the transitional bladder urothelium. Human uroepithelial cells (UROtsa) were grown on transwell inserts; uropathogenicEscherichia coli(UPEC) and neutrophils were added to the transwell system; and the number of migrating neutrophils was evaluated. Reverse transcription-PCR (RT-PCR), immunohistochemistry, and flow cytometry were used to investigate the expression of adenosine receptors, the epithelial adhesion molecule ICAM-1, and the neutrophil integrin CD11b. Levels of proinflammatory interleukin-8 (IL-8) and phosphorylated IκBα were measured by enzyme-linked immunosorbent assays (ELISA) and Luminex assays, respectively. The neutrophils expressed all four adenosine receptor subtypes (A1, A2A, A2B, and A3receptors), but A3receptors were not expressed by UROtsa cells. UPEC stimulated neutrophil transuroepithelial migration, which was significantly decreased in response to the specific A2Areceptor agonist CGS 21680. The inhibitory effect of CGS 21680 on neutrophil migration was reversed by the A2Areceptor antagonist SCH 58261. The production of chemotactic IL-8 and the expression of the adhesion molecule ICAM-1 or CD11b were not significantly affected by CGS 21680. However, a significant decrease in the level of phosporylated IκBα was revealed in response to CGS 21680. In conclusion, UPEC infectionin vitroevoked neutrophil migration through a multilayered human uroepithelium. The UPEC-evoked neutrophil transmigration decreased in response to A2Areceptor activation, possibly through inhibition of NF-κB signaling pathways.
Activation of the Contact System at the Surface of Fusobacterium necrophorum Represents a Possible Virulence Mechanism in Lemièrre's Syndrome
Authors: Holm Karin , Frick Inga-Maria , Björck Lars , Rasmussen Magnus 
Published: June 2011

ABSTRACT

Fusobacterium necrophorum
causes Lemièrre's syndrome, a serious disease with septic thrombophlebitis of the internal jugular vein, pulmonary involvement, and systemic inflammation. The contact system is a link between inflammation and coagulation, and contact activation by the bacteria could therefore contribute to the abnormal coagulation and inflammation seen in patients with Lemièrre's syndrome. In this study,
F. necrophorum
was found to bind radiolabeled high-molecular-weight kininogen (HK), a central component of the contact system. Binding was inhibited by the addition of unlabeled HK and domain D5 of HK but not other components of the contact system, indicating a specific interaction mediated through the D5 region. Binding of HK was significantly reduced after pretreatment of the bacteria with trypsin, suggesting that surface proteins are involved in HK binding. Incubation of the bacteria with human plasma resulted in an HK breakdown pattern suggestive of bradykinin release, and bradykinin was also detected in the supernatant. In addition, we show that factor XI (FXI), another component of the contact system, binds to
F. necrophorum
and that the bound FXI reconstitutes the activated partial thromboplastin time of FXI-deficient plasma. Thrombin activity was detected at the surface of the bacteria following incubation with plasma, indicating that the intrinsic pathway of coagulation is activated at the surface. This activity was completely blocked by inhibitors of the contact system. The combined results show that the contact system is activated at the surface of
F. necrophorum
, suggesting a pathogenic role for this system in Lemièrre's syndrome.