bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly fluorescent GFPm2+‐based genome integration‐proficient promoter probe vector to study Mycobacterium tuberculosis promoters in infected macrophages
Authors: Roy Sougata , Narayana Yeddula , Narayanaswamy Balaji Kithiganahalli , Ajitkumar Parthasarathi 
Published: September 2011

SummaryStudy of activity of cloned promoters in slow‐growing Mycobacterium tuberculosis during long‐term growth conditions in vitro or inside macrophages, requires a genome‐integration proficient promoter probe vector, which can be stably maintained even without antibiotics, carrying a substrate‐independent, easily scorable and highly sensitive reporter gene. In order to meet this requirement, we constructed pAKMN2, which contains mycobacterial codon‐optimized gfpm2+ gene, coding for GFPm2+ of highest fluorescence reported till date, mycobacteriophage L5 attP‐int sequence for genome integration, and a multiple cloning site. pAKMN2 showed stable integration and expression of GFPm2+ from M. tuberculosis and M. smegmatis genome. Expression of GFPm2+, driven by the cloned minimal promoters of M. tuberculosis cell division gene, ftsZ (MtftsZ), could be detected in the M. tuberculosis/pAKMN2‐promoter integrants, growing at exponential phase in defined medium in vitro and inside macrophages. Stable expression from genome‐integrated format even without antibiotic, and high sensitivity of detection by flow cytometry and fluorescence imaging, in spite of single copy integration, make pAKMN2 useful for the study of cloned promoters of any mycobacterial species under long‐term in vitro growth or stress conditions, or inside macrophages.
Cyclic di‐nucleotides: new era for small molecules as adjuvants
Authors: Libanova Rimma , Becker Pablo D. , Guzmán Carlos A. 
Published: September 2011

SummaryThe implementation of vaccination as an empiric strategy to protect against infectious diseases was introduced even before the advent of hygiene and antimicrobials in the medical practice. Nevertheless, it was not until a few decades ago that we really started understanding the underlying mechanisms of protection triggered by vaccination. Vaccines were initially based on attenuated or inactivated organisms. Subunit vaccines were then introduced as more refined formulations, exhibiting improved safety profiles. However, purified antigens tend to be poorly immunogenic and often require the use of adjuvants to achieve adequate stimulation of the immune system. Vaccination strategies, such as mucosal administration, also require potent adjuvants to improve performance. In the 1990s, immunologists found that pathogens could be sensed as ‘danger signals’ by receptors recognizing conserved motifs. Although our knowledge is still limited, tremendous advances were made in the understanding of host defence mechanisms regulated by these evolutionary conserved receptors, and the molecular structures which are recognized by them. This opened a new era in adjuvant development. Some of the latest players arrived to this field are the cyclic di‐nucleotides, which are ubiquitous prokaryotic intracellular signalling molecules. This review is focused on their potential for the development of vaccines and immunotherapies.
Prevalence of diabetic retinopathy in Norway: report from a screening study
Authors: Kilstad Hilde Nygaard , Sjølie Anne Katrine , Gøransson Lasse , Hapnes Rune , Henschien Hans Jørgen , Alsbirk Knud Erik , Fossen Kristian , Bertelsen Geir , Holstad Gro , Bergrem Harald 
Published: September 2011

Abstract.Purpose:  The purpose of the present study was to investigate the prevalence of diabetic retinopathy (DR) in Norway and adherence to the Norwegian Guidelines for screening for diabetic eye disease.Methods:  Two hundred and ninety‐nine people with diabetes were randomly recruited from the patient lists of randomly selected general practitioners from three different regions in Norway. Retinopathy was evaluated from retinal photographs after dilation of the pupils using a red‐free digital camera and visual acuity was measured using the Snellen chart. The patients were interviewed about their ophthalmological and general diabetes control, duration and type of diabetes and medical treatment.Results:  The prevalence of any DR was 28%, 66% for type 1 and 24% for type 2 diabetes. The prevalence of proliferative retinopathy was 38% in type 1 and 1.5% in type 2 diabetes. Two patients (one type 1 and one insulin‐treated type 2) were visually impaired (visual acuity 0.3 or worse in the better eye) because of proliferative DR. Twenty‐six per cent of the patients had never been to an eye examination, and only 69% attended routine eye examinations. Patients who did not attend regular eye screenings were mostly people with type 2 diabetes.Conclusion:  The prevalence of DR was higher than previously reported in Norway. Screening for DR did not follow guidelines in a considerable proportion of the patients with type 2 diabetes. There is place for improvement in the implementation of guidelines for screening for DR for people with type 2 diabetes in Norway.
Intraocular pressure changes following 20G pars‐plana vitrectomy
Authors: Framme Carsten , Klotz Susanne , Wolf‐Schnurrbusch Ute E.K. , Wiedemann Peter , Wolf Sebastian 
Published: September 2011

Abstract.Purpose:  To observe the excursions of short‐term intraocular pressure (IOP) after 20‐G pars‐plana vitrectomy (ppV).Material and methods:  In a prospective study, 851 patients (age: mean 63 ± 15 years) underwent unilateral ppV for various vitreoretinal diseases using different endotamponades [Balanced Salt Solution (BSS) 33.1%, Air 7.2%, SF6 33.6%, silicon oil 5000 cst 26.1%]. Intraocular pressure was measured in all patients before and at 3, 6, 24 and 48 hr after surgery. Survival analysis was performed to determine the cumulative hazard of IOP changes depending on endotamponade and time point after ppV (Log‐Rang ‐ Mantel Cox; p < 0.0001).Results:  At baseline, IOP ranged from 0 to 50 mmHg (mean IOP: 15.3 ± 5.3 mmHg). Mean IOP after surgery revealed a slight elevation (3 hr: 16.5 ± 11.0 mmHg; 6 hr 16.9 ± 9.8 mmHg; 24 hr 19.7 ± 8.0 mmHg; 48 hr 17.3 ± 6.2 mmHg; range: 0–64 mmHg). Silicon oil filling revealed highest mean values at already 3 hr after surgery (21.8 mmHg). Also, BSS filling showed a peak after 3 hr; however, mean values were lower. Equivalent high IOP values as for silicon oil tamponade were found for gas filling; however, maximal peak was reached after 24 hr but not after 3 hr post‐treatment. The cumulative hazard in all patients to reach IOP ≥ 30 mmHg after 24 hr was 23.9%; (IOP ≥ 40 mmHg = 8.2%). Herein, oil filling revealed highest risk at all time points after surgery. The risk of suffering from IOP < 5 mmHg lasting longer than 6 hr was only 1.2% after 20 G vitrectomy.Conclusion:  Intraocular pressure measurements after ppV are important to prevent unintentional high IOP, especially within the early phase (3 hr post‐treatment) in eyes with silicon oil filling. Gas filling leads to prolonged IOP increase (24 hr post‐treatment). Long‐lasting hypotony (≥6 hr) is very rare after 20G vitrectomy.
The effects of an advanced uterine environment on embryonic survival in the mare
Authors: WILSHER S. , LEFRANC A.‐C. , ALLEN W. R. 
Published: September 2011

SummaryReasons for performing the study:During embryo transfer (ET) the equine embryo can tolerate a wide degree of negative asynchrony but positive asynchrony of >2 days usually results in embryonic death. There is still confusion over whether this is due to the inability of the embryo to induce luteostasis or to an inappropriate uterine environment.Objectives:To assess embryo survival and development in an advanced uterine environment.Hypothesis:Embryo–uterine asynchrony, not the embryo's inability to induce luteostasis, is responsible for embryonic death in recipient mares with a >2 days chronologically advanced uterus.Methods:Experiment 1: Thirteen Day 7 embryos were transferred to the uteri of recipient mares with luteal prolongation, occasioned by manual crushing of their own conceptus, such that donor–recipient asynchrony was between +13 and +49 days.Experiment 2: Day 7 embryos were transferred to recipient mares carrying their own conceptus at Days 18 (n = 2), 15 (n = 2), 14 (n = 4), 12 (n = 4) or 11 (n = 4) of gestation. In addition, Day 8 embryos were transferred to 4 pregnant recipient mares on Day 11 of gestation.Results:No pregnancies resulted following transfer of Day 7 embryos to recipients in prolonged dioestrus with asynchronies between +13 and +49 days. However, the use of early pregnant mares as recipients resulted in 5/20 (25%) twin pregnancies, 4 of which came from the transfer of a Day 8 embryo to a Day 11 recipient. All transferred embryos showed retarded growth, with death occurring in 4/5 (80%).Conclusions and potential relevance:The results emphasise the importance of an appropriate uterine environment for embryo growth and the inability of equine embryos to survive transfer to a uterus >2 days advanced even when luteostasis is achieved. It is possible that in normal, non‐ET equine pregnancy, embryo–uterine asynchrony may account for some cases of embryonic death.
In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic
Authors: Takasuga Shinri , Yamamoto Rie , Mafune Shoichi , Sutoh Chiyo , Kominami Katsuya , Yoshida Yoshimasa , Ito Masao , Kinoshita Mine 
Published: September 2011

Abstract

Objectives
The feasibility of transdermal delivery of tramadol, a centrally acting analgesic, by anodal iontophoresis using Ag/AgCl electrodes was investigated in vitro and in vivo.

Methods
To examine the effect of species variation and current strength on skin permeability of tramadol, in-vitro skin permeation studies were performed using porcine ear skin, guinea-pig abdominal skin and hairless mouse abdominal skin as the membrane. In an in-vivo pharmacokinetic study, an iontophoretic patch system was applied to the abdominal skin of conscious guinea pigs with a constant current supply (250 µA/cm2) for 6 h. An intravenous injection group to determine the pharmacokinetic parameters for estimation of the transdermal absorption rate in guinea pigs was also included.

Key findings
The in-vitro steady-state skin permeation flux of tramadol current-dependently increased without significant differences among the three different skin types. In the in-vivo pharmacokinetic study, plasma concentrations of tramadol steadily increased and reached steady state (336 ng/ml) 3 h after initiation of current supply, and the in-vivo steady-state transdermal absorption rate was 499 µg/cm2 per h as calculated by a constrained numeric deconvolution method.

Conclusions
The present study reveals that anodal iontophoresis provides current-controlled transdermal delivery of tramadol without significant interspecies differences, and enables the delivery of therapeutic amounts of tramadol.
Spray-dried oil-in-water emulsion to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac
Authors: Zhang Jianjun , Zheng Zengjuan , Gao Yuan , Zhang Yihua 
Published: September 2011

Abstract

Objectives
Spray-dried emulsion (SDE) was prepared and characterized to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac, currently under preclinical development.

Methods
The intestinal absorption of ZLR-8 was characterized by single pass intestinal perfusion technique to obtain its absorption and permeability parameters. SDE of ZLR-8 was prepared and characterized by particle size measurements and in-vitro release study. Accurate and precise RP-HPLC methods for the detection of ZLR-8 and its metabolite diclofenac were constructed to perform the bioavailability study.

Key findings
It was demonstrated that ZLR-8 was absorbed in the whole intestine, of which the duodenum segment exhibited the largest absorption ability. ZLR-8 can be classified into BCS Class 2. SDE significantly enhanced the intestinal absorption rate of ZLR-8 in duodenum and jejunum but had indistinctive effect on permeability. All concentrations of ZLR-8 in rat plasma was lower than the limit of detection. A bicompartment model gave the best fit to the plasma diclofenac concentration–time curves. Calculated on AUC0–12h, the mean relative bioavailability of SDE was 105.4-fold that of ZLR-8 suspension.

Conclusions
SDE significantly improved the intestinal absorption of ZLR-8 and resulted in a dramatic improvement in its bioavailability.
Prevalence of bisexual behaviour among bridge population of men who have sex with men in China: a meta-analysis of observational studies
Authors: Yun K , Xu J J , Reilly K H , Zhang J , Jiang Y J , Wang N , Shang H 
Published: September 2011

ObjectiveTo integrate the empirical estimates of bisexual behaviour among the bridge population of men who have sex with men (MSM) in China and their HIV and syphilis prevalences stratified by sexual behaviour.MethodsThe Pubmed, Chinese Biomedical, Chinese National Knowledge Infrastructure, VIP, Wanfang and Google Scholar databases were searched to January 2011 to identify relevant articles. Data of eligible citations were extracted by two reviewers. All analyses were performed using Stata 10.0.ResultsForty-nine articles (including 28 739 MSM subjects) met the selection criteria. Aggregated findings indicated that the estimated prevalence of bisexual behaviour among MSM in China is 31.2% (95% CI 28.1% to 34.5%). HIV and syphilis prevalences were 5.4% and 11.4%, respectively, among MSM engaging in bisexual behaviour and 3.8% and 9.3% among MSM only having sex with men. HIV prevalence among MSM engaging in sex with both men and women was significantly higher than in those who only have sex with men (OR 1.30; 95% CI 1.04 to 1.62; p=0.02).ConclusionThere is a high prevalence of bisexual behaviour among MSM in China and bisexual behaviour is significantly associated with increased HIV infection risk. The results of this meta-analysis highlight a critical pattern of HIV transmission among MSM in China and indicate that targeted interventions aimed at encouraging safe sex practices and promoting societal and family acceptance of MSM are urgently needed.
Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients
Authors: Azzopardi Nicolas , Lecomte Thierry , Ternant David , Boisdron-Celle Michelle , Piller Friedrich , Morel Alain , Gouilleux-Gruart Valérie , Vignault-Desvignes Céline , Watier Hervé , Gamelin Erick , Paintaud Gilles 
Published: September 2011

Abstract
Purpose: An ancillary phase II study was conducted to study interindividual variability in cetuximab pharmacokinetics and its influence on progression-free survival (PFS) in metastatic colorectal cancer patients cotreated with irinotecan and 5-fluorouracil.
Experimental Design: Ninety-six patients received cetuximab as an infusion loading dose of 400 mg/m2 followed by weekly infusions of 250 mg/m2. Doses of irinotecan and 5-fluorouracil were adjusted individually. Cetuximab concentrations were measured by ELISA. Compartmental pharmacokinetic parameters were estimated by a population approach, and PFS was analyzed using a Cox model.
Results: Cetuximab pharmacokinetics was best described using a two-compartment model with both first-order and saturable (zero-order) elimination. Estimated pharmacokinetic parameters (% standard error) were as follows: central volume of distribution V1 = 2.96 L (4%), peripheral volume of distribution V2 = 4.65 L (6%), elimination clearance CL = 0.497 L/d (4%), distribution clearance Q = 0.836 L/d (8%), and zero-order elimination rate k0 = 8.71 mg/d (10%). Body surface area influenced V1, V2, and k0. Pretreatment serum albumin influenced CL. Risk of disease progression decreased with cetuximab global clearance (cumulative dose/cumulative area under the concentration versus time curve; P = 0.00016). Median PFS of patients with a cetuximab residual concentration on day 14 below median value was 3.3 months as compared with 7.8 months for the other patients (P = 0.004).
Conclusions: Cetuximab pharmacokinetics in colorectal cancer patients can be described using a model combining linear and nonlinear elimination rates. PFS is influenced by global clearance of cetuximab, a parameter that can be estimated using cetuximab residual concentration on day 14. Clin Cancer Res; 17(19); 6329–37. ©2011 AACR.
MyD88 Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation Independent of Signaling Through Toll-Like Receptors 2 and 4
Authors: Owens A. Phillip , Rateri Debra L. , Howatt Deborah A. , Moore Kathryn J. , Tobias Peter S. , Curtiss Linda K. , Lu Hong , Cassis Lisa A. , Daugherty Alan 
Published: September 2011

Objective—
The purpose of this study was to determine whether myeloid differentiation factor 88 (MyD88) and its related Toll-like receptors (TLRs) 2 and 4 contributed to the development of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and atherosclerosis.

Methods and Results—

AngII was infused into either apoE
−/−
or LDL receptor (LDLR)
−/−
male mice that were either MyD88
+/+
or
−/−
. MyD88 deficiency profoundly reduced AngII-induced AAAs and atherosclerosis in both strains. To define whether deficiency of specific TLRs had similar effects, AngII was infused into LDLR
−/−
mice that were also deficient in either TLR2 or TLR4. TLR2 deficiency had no effect on AAA development but inhibited atherosclerosis. In contrast, TLR4 deficiency attenuated both AAAs and atherosclerosis. To resolve whether MyD88 and TLR4 exerted their effects through cells of hematopoietic lineage, LDLR
−/−
mice were lethally irradiated and repopulated with bone marrow-derived cells from either MyD88 or TLR4 strains. MyD88 deficiency in bone marrow-derived cells profoundly reduced both AngII-induced AAAs and atherosclerosis. However, TLR4 deficiency in bone marrow-derived cells had no effect on either pathology.

Conclusion—
These studies demonstrate that MyD88 deficiency in leukocytes profoundly reduces AngII-induced AAAs and atherosclerosis via mechanisms independent of either TLR2 or TLR4.
Body Weight After Stroke
Authors: Scherbakov Nadja , Dirnagl Ulrich , Doehner Wolfram 
Published: September 2011

Background and Purpose—
Outcome after acute stroke is determined to a large extent by poststroke complications. Nutritional status and metabolic balance may substantially contribute to outcome after stroke. Key mechanisms of stroke pathophysiology can induce systemic catabolic imbalance with impaired metabolic efficiency and degradation of body tissues.

Summary—
Tissue wasting, sarcopenia, and cachexia may impair and delay poststroke rehabilitation and worsen the prognosis. Although current guidelines for secondary prevention after stroke recommend weight reduction, increasing evidence suggests that patients who are overweight and mildly obese may actually have a better outcome. An “obesity paradox” has been identified to describe the contrasting impact of being overweight in patients with chronic illness compared with healthy populations. We present an overview on the metabolic regulation in patients with stroke and evaluate current data on the impact of body weight and weight change after stroke. The emerging picture suggests that being overweight and obese may impact patients with stroke differently than it does healthy subjects.

Conclusions—
We propose that current knowledge on obesity and its management in primary prevention cannot be transferred to patients with established stroke. Systematic studies on changes in body composition after stroke and on treatment options are warranted to establish the pathophysiology and evidence-driven management of nutritional status in these patients.
Sea-Level Assessment of Dynamic Cerebral Autoregulation Predicts Susceptibility to Acute Mountain Sickness at High Altitude
Authors: Cochand Nicholas J. , Wild Michael , Brugniaux Julien V. , Davies Peter J. , Evans Kevin A. , Wise Richard G. , Bailey Damian M. 
Published: September 2011

Background and Purpose—
Dynamic cerebral autoregulation is impaired in subjects who develop acute mountain sickness (AMS), a neurological disorder characterized by headache. The present study examined if the normoxic sea-level measurement of dynamic cerebral autoregulation would predict subsequent susceptibility to AMS during rapid ascent to terrestrial high altitude.

Methods—
A dynamic cerebral autoregulation index was determined in 18 subjects at sea level from continuous recordings of middle cerebral artery blood flow velocity (Doppler ultrasonography) and arterial blood pressure (finger photoplethysmography) after recovery from transiently induced hypotension. Six hours after passive ascent to 3800 m (Mt Elbrus, Russia), the Lake Louise and Environmental Symptoms Cerebral Symptoms questionnaires were used to assess AMS.

Results—

AMS scores increased markedly at high-altitude (Lake Louise: +3±2 points,
P
=0.001 and Environmental Symptoms Cerebral Symptoms: +0.6±0.9 points,
P
=0.0003 versus sea level). Inverse relationships were observed between the sea-level autoregulation index score and the high-altitude-induced increases in the Lake Louise (
r
=−0.62,
P
=0.007) and Environmental Symptoms Cerebral Symptoms (
r
=−0.78,
P
=0.01) scores. One subject with a history of high-altitude pulmonary and cerebral edema presented with the lowest sea-level autoregulation index score (3.7 versus group: 6.2±1.0 points) and later developed high-altitude cerebral edema at 4800 m during the summit bid.

Conclusions—
These findings suggest that a lower baseline autoregulation index may be considered a potential risk factor for AMS. This laboratory measurement may prove a useful screening tool for the expedition doctor when considering targeted pharmacological prophylaxis in individuals deemed “AMS-susceptible.”
Extent of Hypoattenuation on CT Angiography Source Images in Basilar Artery Occlusion
Authors: Puetz Volker , Khomenko Andrei , Hill Michael D. , Dzialowski Imanuel , Michel Patrik , Weimar Christian , Wijman Christine A.C. , Mattle Heinrich P. , Engelter Stefan T. , Muir Keith W. , Pfefferkorn Thomas , Tanne David , Szabo Kristina , Kappelle L. Jaap , Algra Ale , von Kummer Ruediger , Demchuk Andrew M. , Schonewille Wouter J. 
Published: September 2011

Background and Purpose—
The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS).

Methods—
BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0–3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0–2).

Results—
Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS ≥8. Patients with a pc-ASPECTS ≥8 more often had a favorable outcome than patients with a pc-ASPECTS <8 (crude RR, 1.7; 95% CI, 0.98–3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS ≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8–2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5–0.98) and functional independence (RR, 2.0; 95% CI, 1.1–3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2–7.5).

Conclusions—
pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.