bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methamphetamine Enhances Cryptococcus neoformans Pulmonary Infection and Dissemination to the Brain
Authors: Patel Dhavan , Desai Gunjan M. , Frases Susana , Cordero Radames J. B. , DeLeon-Rodriguez Carlos M. , Eugenin Eliseo A. , Nosanchuk Joshua D. , Martinez Luis R. 
Published: July 2013

ABSTRACT

Methamphetamine (METH) is a major addictive drug of abuse in the United States and worldwide, and its use is linked to HIV acquisition. The encapsulated fungus
Cryptococcus neoformans
is the most common cause of fungal meningitis in patients with AIDS. In addition to functioning as a central nervous system stimulant, METH has diverse effects on host immunity. Using a systemic mouse model of infection and
in vitro
assays in order to critically assess the impact of METH on
C. neoformans
pathogenesis, we demonstrate that METH stimulates fungal adhesion, glucuronoxylomannan (GXM) release, and biofilm formation in the lungs. Interestingly, structural analysis of the capsular polysaccharide of METH-exposed cryptococci revealed that METH alters the carbohydrate composition of this virulence factor, an event of adaptation to external stimuli that can be advantageous to the fungus during pathogenesis. Additionally, we show that METH promotes
C. neoformans
dissemination from the respiratory tract into the brain parenchyma. Our findings provide novel evidence of the impact of METH abuse on host homeostasis and increased permissiveness to opportunistic microorganisms.

IMPORTANCE
Methamphetamine (METH) is a major health threat to our society, as it adversely changes people’s behavior, as well as increases the risk for the acquisition of diverse infectious diseases, particularly those that enter through the respiratory tract or skin. This report investigates the effects of METH use on pulmonary infection by the AIDS-related fungus
Cryptococcus neoformans
. This drug of abuse stimulates colonization and biofilm formation in the lungs, followed by dissemination of the fungus to the central nervous system. Notably,
C. neoformans
modifies its capsular polysaccharide after METH exposure, highlighting the fungus’s ability to adapt to environmental stimuli, a possible explanation for its pathogenesis. The findings may translate into new knowledge and development of therapeutic and public health strategies to deal with the devastating complications of METH abuse.
IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A
Streptococcus
Authors: Okumura Cheryl Y. M. , Anderson Ericka L. , Döhrmann Simon , Tran Dan N. , Olson Joshua , von Pawel-Rammingen Ulrich , Nizet Victor 
Published: July 2013

ABSTRACT

The Mac/IdeS protein of group A
Streptococcus
(GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds.

IMPORTANCE
Group A
Streptococcus
(GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly contribute to the ability of the bacteria to survive white blood cell killing or produce invasive infection in the mouse. These data underscore the importance of correlating studies on virulence factor function with physiologic expression levels and the complexity of streptococcal pathogenesis and contribute to our overall understanding of how GAS causes disease.
How patients want to engage with their personal health record: a qualitative study
Authors: Kerns John William , Krist Alexander H , Longo Daniel R , Kuzel Anton J , Woolf Steven H 
Published: July 2013

ObjectiveTo assess factors related to use and non-use of a sophisticated interactive preventive health record (IPHR) designed to promote uptake of 18 recommended clinical preventive services; little is known about how patients want to use or be engaged by such advanced information tools.DesignDescriptive and interpretive qualitative analysis of transcripts and field notes from focus groups of the IPHR users and of patients who were invited but did not use the IPHR (non-users). Grounded theory techniques were then applied via an editing approach for key emergent themes.SettingPrimary care patients in eight practices of the Virginia Ambulatory Care Outcomes Research Network (ACORN).ParticipantsThree focus groups involved a total of 14 IPHR users and two groups of non-users totalled 14 participants.Outcomes/resultsFor themes identified (relevance, trust and functionality) participants indicated that endorsement and use of the IPHR by their personal clinician was vital. In particular, participants’ comments linked the IPHR use to: (1) integrating the IPHR into current care, (2) promoting effective patient–clinician encounters and communication and (3) their confidence in the accuracy, security and privacy of the information.ConclusionsIn addition to patients’ stated desires for advanced functionality and information accuracy and privacy, successful adoption of the IPHRs by primary care patients depends on such technology's relevance, and on its promotion via integration with primary care practices’ processes and the patient–clinician relationship. Accordingly, models of technological success and adoption, when applied to primary care, may need to include the patient–clinician relationship and practice workflow. These findings are important for healthcare providers, the information technology industry and policymakers who share an interest in encouraging patients to use personal health records.Trial RegistrationClinicaltrials.gov identifier:NCT00589173
Oral Naftopidil Suppresses Human Renal-Cell Carcinoma by Inducing G1 Cell-Cycle Arrest in Tumor and Vascular Endothelial Cells
Authors: Iwamoto Yoichi , Ishii Kenichiro , Sasaki Takeshi , Kato Manabu , Kanda Hideki , Yamada Yasushi , Arima Kiminobu , Shiraishi Taizo , Sugimura Yoshiki 
Published: July 2013

Abstract
Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, several targeting agents are being investigated. However, the efficacy of current regimens is generally insufficient for their toxicity and poor overall response rates. We have recently reported that naftopidil exerts growth-inhibitory effects on human prostate cancer cells. In this study, we investigated the biochemical mechanisms by which naftopidil produces growth-inhibitory and antiangiogenic effects on RCC. We first tested the effects of naftopidil on the proliferation of ACHN and Caki-2 RCC cells. Next, we set up a model simulating the tumor microenvironment, in which ACHN cells were grafted onto the renal capsule of mice. We then tested the effects of naftopidil on human umbilical vein endothelial cells' cell proliferation and Matrigel plug vascularization. Finally, to establish the antitumor activity of naftopidil on RCC, we tested the antitumor effects of naftopidil on excised tumor specimens from 20 patients with RCC that were grafted beneath the renal capsule of mice. Naftopidil showed similar in vitro growth-inhibitory effects on all cell lines. Fluorescence-activated cell sorting analysis revealed an increase in G1 cell-cycle arrest in all naftopidil-treated cell lines. In vivo tumorigenic studies showed a significant reduction of ACHN tumor weight, Ki-67 index, and microvessel density (MVD) in naftopidil-treated mice. Naftopidil attenuated neovascularization in an in vivo Matrigel plug assay. Studies in mouse xenograft models also showed a significant MVD reduction in naftopidil-treated excised human RCC. The growth-inhibitory effects of naftopidil suggest it may be a novel anticancer agent and a potential preventive option for RCC. Cancer Prev Res; 6(9); 1000–6. ©2013 AACR.
Global Variation in Quality of Care Among Patients Hospitalized With Acute Heart Failure in an International Trial
Authors: Howlett Jonathan G. , Ezekowitz Justin A. , Podder Mohua , Hernandez Adrian F. , Diaz Rafael , Dickstein Kenneth , Dunlap Mark E. , Corbalán Ramón , Armstrong Paul W. , Starling Randall C. , O’Connor Christopher M. , Califf Robert M. , Fonarow Gregg C. 
Published: July 2013

Background—
Translation of evidence-based heart failure (HF) therapies to clinical practice is incomplete and may vary internationally. We examined common measures of quality of care in patients enrolled in the international Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial.

Methods and Results—

Patients were admitted to 398 hospitals for acute HF in 5 regions (North America, n=3149; Latin America, n=658; Asia Pacific, n=1744; Central Europe, n=966; and Western Europe, n=490). Predefined quality indicators assessed at hospital discharge included the following: medications (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-blockers, aldosterone antagonists, hydralazine/nitrates, statin therapy, and warfarin), use (or planned use) of implantable intracardiac devices, and blood pressure control (<140/90 mm Hg). We determined regional variations in quality indicators as well as the temporal variation of these indicators during the course of the trial. There was significant variation in conformity among different quality indicators, ranging from 0% to 89%. Of all potential performance opportunities, 19 076 of 32 268 (59%) were met, with Central Europe highest at 64%, followed by North America (63%), Western Europe (61%), Latin America (56%), and Asia Pacific (51%;
P
<0.0001). North America, Central Europe, and Asia Pacific regions demonstrated a modest increase in quality indicator conformity over time, although there was no significant change in other regions.

Conclusions—
Quality of care for patients hospitalized with acute HF varies and remains suboptimal even within a randomized clinical trial, which included quality improvement interventions. Specific measures designed to improve performance measures should be implemented even within multicenter clinical trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00475852.
Heterogeneity in Lung
18
FDG Uptake in Pulmonary Arterial Hypertension
Authors: Zhao Lan , Ashek Ali , Wang Lei , Fang Wei , Dabral Swati , Dubois Olivier , Cupitt John , Pullamsetti Soni Savai , Cotroneo Emanuele , Jones Hazel , Tomasi Gianpaolo , Nguyen Quang-De , Aboagye Eric O. , El-Bahrawy Mona A. , Barnes Gareth , Howard Luke S. , Gibbs J. Simon R. , Gsell Willy , He Jian-Guo , Wilkins Martin R. 
Published: July 2013

Background—
Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH.

Methods and Results—

Dynamic positron emission tomography imaging with fluorine-18–labeled 2-fluoro-2-deoxyglucose (
18
FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71;
P
<0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung
18
FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung
18
FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular
18
FDG uptake; both were reduced by dicholoroacetate and imatinib.

Conclusions—

Some patients with IPAH exhibit increased lung
18
FDG uptake.
18
FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.
Risk of Ischemic Cerebrovascular and Coronary Events in Adult Users of Anticonvulsant Medications in Routine Care Settings
Authors: Patorno Elisabetta , Glynn Robert J. , Hernandez‐Diaz Sonia , Avorn Jerry , Wahl Peter M. , Bohn Rhonda L. , Mines Daniel , Liu Jun , Schneeweiss Sebastian 
Published: July 2013

Background
Older‐generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting.

Methods and Results

This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (
PS
) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High‐dimensional propensity score (hd
PS
)–matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a
PS
‐matched population of 22 864 treatment episodes, the rate ratio (
RR
) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95%
CI
, 0.90‐1.65). The
RR
moved to 0.99 (95%
CI
, 0.73‐1.33) with adjustment for hd
PS
matching (
RR
, 1.47; 95%
CI
, 0.95‐2.28 for cerebrovascular events;
RR
, 0.70; 95%
CI
, 0.47‐1.05 for coronary events).

Conclusions
In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns.
Endovascular Therapy for Asymptomatic Unruptured Intracranial Aneurysms
Authors: Shigematsu Tomoyoshi , Fujinaka Toshiyuki , Yoshimine Toshiki , Imamura Hirotoshi , Ishii Akira , Sakai Chiaki , Sakai Nobuyuki 
Published: July 2013

Background and Purpose—
National registration studies (the Japanese Registry of Neuroendovascular Therapy [JR-NET] and JR-NET2) have determined the current status and outcomes of neuroendovascular therapy (neuro-EVT). We analyzed short-term outcomes of EVT for asymptomatic unruptured intracranial aneurysms (UIAs).

Methods—
We extracted periprocedural information about EVT for 4767 asymptomatic UIAs from 31 968 registered procedural records of all EVT in the JR-NET and JR-NET2 databases. We assessed the features of the aneurysms and procedures, immediate radiographic findings, procedure-related complications, and clinical outcomes at 30 days after the procedures.

Results—
We located 80.0% of UIAs in the anterior circulation, and the most frequent were paraclinoid. The diameter of 2.5%, 32.9%, 51.9%, 12.0%, and 0.7% of the UIAs was <3, 3 to 4, 5 to 9, 10 to 19, and >20 mm, respectively. EVT failed in only 2.1%. Adjunctive techniques were applied in 54.8% of procedures. Pre- and postprocedural antiplatelet agents were prescribed in 85.6% and 84.0%, respectively, of the procedures. The immediate radiographic outcomes of 57.7%, 31.9%, and 10.0% of the UIAs comprised complete occlusion, residual necks, and residual aneurysms, respectively. Complications that were associated with 9.1% of procedures comprised 2.0% hemorrhagic and 4.6% ischemic, and the 30-day morbidity and mortality rates were 2.12% and 0.31%, respectively.

Conclusions—
The radiographic results of EVT for asymptomatic UIAs in Japan were acceptable, with low mortality and morbidity rates.
Serum Fatty Acids and Incidence of Ischemic Stroke Among Postmenopausal Women
Authors: Yaemsiri Sirin , Sen Souvik , Tinker Lesley F. , Robinson Whitney R. , Evans Rhobert W. , Rosamond Wayne , Wasserthiel-Smoller Sylvia , He Ka 
Published: July 2013

Background and Purpose—
Although studies have linked types of fatty acids with coronary heart disease, data on individual fatty acids and risk of ischemic stroke are limited. We aimed to examine the associations between serum fatty acid concentrations and incidence of ischemic stroke and its subtypes.

Methods—
We conducted a prospective case–control study nested in the Women’s Health Initiative Observational Study cohort of postmenopausal US women aged 50 to 79 years. Between 1993 and 2003, incident cases of ischemic stroke were matched 1:1 to controls on age, race, and length of follow-up (964 matched pairs). Conditional logistic regression was used to estimate odds ratios and 99.9% confidence intervals (CI) for ischemic stroke and its subtypes.

Results—

The multivariable-adjusted odds ratios and 99.9% CI of ischemic stroke associated with a 1-SD increment in serum fatty acid concentration were 1.38 (99.9% CI, 1.05–1.83) for linoelaidic acid (18:2
tt
, SD=0.04%), 1.27 (99.9% CI, 1.06–1.51) for palmitic acid (16:0, SD=2.74%), 1.20 (99.9% CI, 1.01–1.43) for oleic acid (18:1n9, SD=2.32%), 0.72 (99.9% CI, 0.59–0.87) for docosapentaenoic acid (22:5n3, SD=0.18%), 0.72 (99.9% CI, 0.59–0.87) for docosahexaenoic acid (22:6n3, SD=0.91%), and 0.81 (99.9% CI, 0.67–0.98) for arachidonic acid (20:4n6, SD=2.02%). These associations were generally consistent for atherothrombotic and lacunar stroke but not cardioembolic stroke.

Conclusions—

These findings suggest that individual serum
trans
, saturated, and monounsaturated fatty acids are positively associated with particular ischemic stroke subtypes, whereas individual n3 and n6 polyunsaturated fatty acids are inversely associated.
Predictors of Stroke in Patients With Impaired Glucose Tolerance
Authors: Preiss David , Giles Thomas D. , Thomas Laine E. , Sun Jie-Lena , Haffner Steven M. , Holman Rury R. , Standl Eberhard , Mazzone Theodore , Rutten Guy E. , Tognoni Gianni , Chiang Fu-Tien , McMurray John J.V. , Califf Robert M. 
Published: July 2013

Background and Purpose—
Risk factors for stroke are well-established in general populations but sparsely studied in individuals with impaired glucose tolerance.

Methods—
We identified predictors of stroke among participants with impaired glucose tolerance in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Cox proportional-hazard regression models were constructed using baseline variables, including the 2 medications studied, valsartan and nateglinide.

Results—
Among 9306 participants, 237 experienced a stroke over 6.4 years. Predictors of stroke included classical risk factors such as existing cerebrovascular and coronary heart disease, higher pulse pressure, higher low-density lipoprotein cholesterol, older age, and atrial fibrillation. Other factors, including previous venous thromboembolism, higher waist circumference, lower estimated glomerular filtration rate, lower heart rate, and lower body mass index, provided additional important predictive information, yielding a C-index of 0.72. Glycemic measures were not predictive of stroke. Variables associated with stroke were similar in participants with no prior history of cerebrovascular disease at baseline.

Conclusions—
The most powerful predictors of stroke in patients with impaired glucose tolerance included a combination of established risk factors and novel variables, such as previous venous thromboembolism and elevated waist circumference, allowing moderately effective identification of high-risk individuals.
Concomitant Headache Influences Long-term Prognosis After Acute Cerebral Ischemia of Noncardioembolic Origin
Authors: Maino Alberto , Algra Ale , Koudstaal Peter J. , van Zwet Erik W. , Ferrari Michel D. , Wermer Marieke J.H. 
Published: July 2013

Background and Purpose—
Acute cerebral ischemia is frequently associated with headache. It is unknown whether concomitant headache reflects a partly different pathogenesis, and thus, may influence long-term prognosis after stroke. Here, we compared the long-term risk of recurrent vascular events in patients in whom a transient ischemic attack or minor ischemic stroke of noncardioembolic origin was associated with headache with those without headache.

Methods—
We used data from the Life Long After Cerebral ischemia (LiLAC) cohort. Participants were grouped on the basis of presence or absence of headache at presentation. We calculated the hazard ratios (HRs) and corresponding 95% confidence intervals (CI) for any first vascular event (primary outcome) or any cardiac or cerebral event (secondary outcomes). Adjustments were made for baseline clinical characteristics.

Results—
Of 2473 participants, 420 (17%) experienced headache during the acute event. Median follow-up was 14.1 years. For the primary outcome, the crude HR of headache versus no headache was 0.75 (95% CI, 0.66–0.89) and the adjusted HR 0.83 (95% CI, 0.71–0.97). For cardiac events the adjusted HR was 0.88 (95% CI, 0.67–1.14) and for cerebral events, 0.97 (95% CI, 0.76–1.24). The ratio of cardiac versus cerebral events, however, did not differ between the 2 groups. Participants with headache were at lower risk of vascular death (adjusted HR, 0.73; 95% CI, 0.61–0.87).

Conclusions—
Patients who experienced headache in association with a transient ischemic attack or minor ischemic stroke have a better vascular prognosis than those without concomitant headache. This may, at least partly, reflect a different pathogenesis.