bluuebunny/crossref_metadata_2025_split huggingface dataset:
Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: A modelling analysis based on a nationwide cohort study
Authors: Banerjee Amitava , Lane Deirdre A. , Torp-Pedersen Christian , Lip Gregory Y. H. 
Published: December 2011

SummaryThe concept of net clinical benefit has been used to quantify the balance between risk of ischaemic stroke (IS) and risk of intracranial haemorrhage (ICH) with the use oral anticoagulant therapy (OAC) in the setting of non-valvular atrial fibrillation (AF), and has shown that patients at highest risk of stroke and thromboembolism gain the greatest benefit from OAC with warfarin. There are no data for the new OACs, that is, dabigatran, rivaroxaban and apixaban, as yet. We calculated the net clinical benefit balancing IS against ICH using data from the Danish National Patient Registry on patients with non-valvular AF between 1997–2008, for dabigatran, rivaroxaban and apixaban on the basis of recent clinical trial outcome data for these new OACs. In patients with CHADS2=0 but at high bleeding risk, apixaban and dabigatran 110 mg bid had a positive net clinical benefit. At CHA2DS2-VASc=1, apixaban and both doses of dabigatran (110 mg and 150 mg bid) had a positive net clinical benefit. In patients with CHADS2 score≥1 or CHA2DS2-VASc≥2, the three new OACs (dabigatran, rivaroxaban and apixaban) appear superior to warfarin for net clinical benefit, regardless of risk of bleeding. When risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit than warfarin. In the absence of head-to-head trials for these new OACs, our analysis may help inform decision making processes when all these new OACs become available to clinicians for stroke prevention in AF. Using ‘real world’ data, our modelling analysis has shown that when the risk of bleeding and stroke are both high, all three new drugs appear to have a greater net clinical benefit compared to warfarin.The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.
Atrioventricular Nodal Ablation in Atrial Fibrillation
Authors: Chatterjee Neal A. , Upadhyay Gaurav A. , Ellenbogen Kenneth A. , McAlister Finlay A. , Choudhry Niteesh K. , Singh Jagmeet P. 
Published: December 2011

Background—
In the treatment of patients with refractory atrial fibrillation (AF), the safety and efficacy of atrioventricular nodal ablation (AVNA) versus pharmacotherapy alone remains unclear. Additionally, the impact of AVNA in patients with reduced systolic function is of growing interest.

Methods and Results—
A total of 5 randomized or prospective trials were included for efficacy review (314 patients), 11 studies for effectiveness review (810 patients), and 47 studies for safety review (5632 patients). All-cause mortality was similar between AVNA and medical therapy (3.1% versus 3.3%; relative risk ratio, 1.05; 95% confidence interval [CI], 0.29–3.85). There was no significant difference in exercise duration or ejection fraction (EF) with AVNA relative to pharmacotherapy. In subgroup analysis, patients with baseline systolic dysfunction (116 patients; mean EF, 44%) showed significant relative improvement in EF after AVNA (+4% greater; 95% CI, 3.11–4.89). In pooled observational analysis, AVNA was also associated with significant improvement in EF only in patients with systolic dysfunction (+7.44%; 95% CI, 5.4–9.5). The incidence of procedure-related mortality (0.27%) and malignant arrhythmia (0.57%) was low. At mean follow-up of 26.5 months, the incidence of sudden cardiac death after AVNA was 2.1%. There was significant heterogeneity in quality-of-life scales used; compared with pharmacotherapy, AVNA was associated with significant improvement in several symptoms (palpitations, dyspnea).

Conclusions—
In the management of refractory AF, AVNA is associated with improvement in symptoms and quality of life, with a low incidence of procedure morbidity. In patients with reduced systolic function, AVNA demonstrates small but significantly improved echocardiographic outcomes relative to medical therapy alone.
Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition
Authors: Sun Qian , Prasad Ram , Rosenthal Eben , Katiyar Santosh K 
Published: December 2011

Abstract

Background
Head and neck squamous cell carcinoma (HNSCC) is responsible for over 20,000 deaths every year in United States. Most of the deaths are due, in large part, to its propensity to metastasize. We have examined the effect of bioactive component grape seed proanthocyanidins (GSPs) on human cutaneous HNSCC cell invasion and the molecular mechanisms underlying these effects using SCC13 cell line as an in vitro model.

Methods
The therapeutic effects of GSPs on cancer cell invasion were studied using Boyden chamber and wound healing assays. The effects of GSPs on the levels of various proteins related with cancer cell invasion were determined using western blot analysis.

Results
Using in vitro cell invasion assays, we observed that treatment of SCC13 cells with GSPs resulted in a concentration-dependent inhibition of cell invasion of these cells, which was associated with a reduction in the levels of epidermal growth factor receptor (EGFR). Treatment of cells with gefitinib and erlotinib, inhibitors of EGFR, or transient transfection of SCC13 cells with EGFR small interfering RNA, also inhibited invasion of these cells. The inhibition of cell invasion by GSPs was associated with the inhibition of the phosphorylation of ERK1/2, a member of mitogen-activated protein kinase family. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the invasion potential of SCC13 cells. Additionally, inhibition of human cutaneous HNSCC cell invasion by GSPs was associated with reversal of epithelial-to-mesenchymal transition (EMT) process, which resulted in an increase in the levels of epithelial biomarker (E-cadherin) while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in cells. Similar effect on EMT biomarkers was also observed when cells were treated with erlotinib.

Conclusion
The results obtained from this study indicate that grape seed proanthocyanidins have the ability to inhibit the invasion of human cutaneous HNSCC cells by targeting the EGFR expression and reversing the process of epithelial-to-mesenchymal transition. These data suggest that GSPs can be developed as a complementary and alternative medicine for the prevention of invasion/metastasis of HNSCC cells.
Micro-regional planning: evidence-based community buy-in for health development in five of Mexico’s poorest rural districts
Authors: Arrizón Ascencio Villegas , Andersson Neil , Ledogar Robert J 
Published: December 2011

Abstract

Background
Community participation was a core tenet of Primary Health Care as articulated in the 1970s. How this could be generated and maintained was less clear. This historical article describes development of protocols for evidence-based community mobilisation in five local administrative units (municipios) in the Mexican state of Guerrero between 1992 and 1995.

Methods
A sample of five to eight sentinel sites represented each of the most impoverished municipalities of the poorest five of the state's seven regions. A 1992 baseline survey of diarrhoea and its actionable determinants provided the substrate for discussion with local planners and communities. Municipal planners used different strategies to promote participation. In one municipality, new health committees took control of water quality. In another, municipal authorities hired health promoters; a song promoted oral rehydration, and house-to-house interpersonal discussions promoted chlorination. In the poorest and most mountainous municipality, radio casera (home-made radio) soap operas used local "stars". In the largest and most disparate municipality, a child-to-family scheme relied on primary and secondary school teachers. The research team assessed outcomes at intervals and used the results to reinforce local planning and action.

Results
Diarrhoea rates declined in all five municipalities, and there were several positive intermediate outcomes from the communication strategies – changing knowledge, household practices and uptake of services. There was a strong link between specific contents of the communication package and the changing knowledge or practices.

Conclusions
Apart from these evidence-based interventions, other factors probably contributed to the decline of childhood diarrhoea. But, by monitoring implementation of planning decisions and the impact this has at community level, micro-regional planning can stimulate and reinforce actions likely to improve the health of communities. The process empowered municipalities to get access to more resources from the state government and international agencies.
Spleen rates and infant parasite rates as surveillance tool for malaria control in remote hard to reach areas of central India
Authors: Shukla Manmohan , Singh Neeru , Singh Mrigendra P 
Published: December 2011

Abstract

Background
Malaria due to both Plasmodium falciparum and Plasmodium vivax is a major public health problem in India. The quantification of malaria transmission for the classification of malaria risk has long been a concern for epidemiologists. Results are presented from 30 cross-sectional surveys which measured spleen rates (SR) and infant parasite rates (IPR) in the forested districts of Madhya Pradesh during malaria outbreaks to assess whether both IPR and SR can still be used as indicators of malaria endemicity as spleen examination has lost much of its value as an epidemiological indicator in areas where anti-malarials drugs are widely used.

Methods
Rapid fever surveys were carried out from door to door and all suspected malaria cases in the entire population of a village were screened for malaria parasites on the basis of clinical symptoms such as fever, chill, rigor, headache and body ache etc. Children between 2 and 9 years were examined for enlarged spleen according to Hacketts method. Finger prick blood smears were collected from all children with enlarged spleen with or without fever after obtaining written informed consent following institutional ethical guidelines. Infants less than 1 year were also screened for malaria with or without fever.

Results
Since malaria is local and focal, in some areas the outbreak waned quickly in few months and in some areas continued for 3 to 4 years. The analysis of trend revealed that when IPR decline over the years as a result of malaria intervention measures, SR also decline. In case splenomegaly continues without diminution in size, it is probably due to recrudescence or relapse, although it is not possible to separate malaria parasite species on the basis of SR.

Conclusion
Both the tools are of immense value in evaluating and assessing the malaria situation especially in remote areas where sophisticated molecular and serological techniques are difficult to establish. Therefore, in forested areas malaria surveillance system will require adoption of multiple approaches that have proven effective now or in the past.
Temporal Control of Gene Deletion in Sensory Ganglia Using a Tamoxifen-Inducible Advillin-CreERT2 Recombinase Mouse
Authors: Lau Joanne , Minett Michael S , Zhao Jing , Dennehy Ulla , Wang Fan , Wood John N , Bogdanov Yury D 
Published: December 2011

Background: Tissue-specific gene deletion has proved informative in the analysis of pain pathways. Advillin has been shown to be a pan-neuronal marker of spinal and cranial sensory ganglia. We generated BAC transgenic mice using the Advillin promoter to drive a tamoxifen-inducible CreERT2 recombinase construct in order to be able to delete genes in adult animals. We used a floxed stop ROSA26LacZ reporter mouse to examine functional Cre expression, and analysed the behaviour of mice expressing Cre recombinase. Results: We used recombineering to introduce a CreERT2 cassette in place of exon 2 of the Advillin gene into a BAC clone (RPCI23-424F19) containing the 5' region of the Advillin gene. Transgenic mice were generated using pronuclear injection. The resulting AvCreERT2 transgenic mice showed a highly specific expression pattern of Cre activity after tamoxifen induction. Recombinase activity was confined to sensory neurons and no expression was found in other organs. Less than 1% of neurons showed Cre expression in the absence of tamoxifen treatment. Five-day intraperitoneal treatment with tamoxifen (2 mg per day) induced Cre recombination events in ≈90% of neurons in dorsal root and cranial ganglia. Cell counts of dorsal root ganglia (DRG) from transgenic animals with or without tamoxifen treatment showed no neuronal cell loss. Sensory neurons in culture showed ≈70% induction after 3 days treatment with tamoxifen. Behavioural tests showed no differences between wildtype, AvCreERT2 and tamoxifen-treated animals in terms of motor function, responses to light touch and noxious pressure, thermal thresholds as well as responses to inflammatory agents. Conclusions: Our results suggest that the inducible pan-DRG AvCreERT2 deleter mouse strain is a useful tool for studying the role of individual genes in adult sensory neuron function. The pain phenotype of the Cre-induced animal is normal; therefore any alterations in pain processing can be unambiguously attributed to loss of the targeted gene.
DnaA and the timing of chromosome replication in Es-cherichia coli as a function of growth rate
Authors: Grant Matthew AA , Saggioro Chiara , Ferrari Ulisse , Bassetti Bruno , Sclavi Bianca , Cosentino Lagomarsino Marco 
Published: December 2011

Abstract

Background
In Escherichia coli, overlapping rounds of DNA replication allow the bacteria to double in faster times than the time required to copy the genome. The precise timing of initiation of DNA replication is determined by a regulatory circuit that depends on the binding of a critical number of ATP-bound DnaA proteins at the origin of replication, resulting in the melting of the DNA and the assembly of the replication complex. The synthesis of DnaA in the cell is controlled by a growth-rate dependent, negatively autoregulated gene found near the origin of replication. Both the regulatory and initiation activity of DnaA depend on its nucleotide bound state and its availability.

Results
In order to investigate the contributions of the different regulatory processes to the timing of initiation of DNA replication at varying growth rates, we formulate a minimal quantitative model of the initiator circuit that includes the key ingredients known to regulate the activity of the DnaA protein. This model describes the average-cell oscillations in DnaA-ATP/DNA during the cell cycle, for varying growth rates. We evaluate the conditions under which this ratio attains the same threshold value at the time of initiation, independently of the growth rate.

Conclusions
We find that a quantitative description of replication initiation by DnaA must rely on the dependency of the basic parameters on growth rate, in order to account for the timing of initiation of DNA replication at different cell doubling times. We isolate two main possible scenarios for this, depending on the roles of DnaA autoregulation and DnaA ATP-hydrolysis regulatory process. One possibility is that the basal rate of regulatory inactivation by ATP hydrolysis must vary with growth rate. Alternatively, some parameters defining promoter activity need to be a function of the growth rate. In either case, the basal rate of gene expression needs to increase with the growth rate, in accordance with the known characteristics of the dnaA promoter. Furthermore, both inactivation and autorepression reduce the amplitude of the cell-cycle oscillations of DnaA-ATP/DNA.
The submental flap for oral cavity reconstruction: Extended indications and technical refinements
Authors: Amin Ayman A , Sakkary Mostafa A , Khalil Ashraf A , Rifaat Mohammmed A , Zayed Sherif B 
Published: December 2011

Abstract

Background and purpose
The submental flap is gaining popularity as a simple technique for reconstruction of small to moderate size defects of the oral cavity. However, its role in composite defects involving the jaw is not clearly defined. Indeed, controversy exists about the flap's interference with an oncologically sound neck dissection

Patients and Methods
A total of 21 patients with oral cavity cancers over a three year period were included. All patients underwent surgical resection and immediate reconstruction with submental flap except one patient who had delayed reconstruction with reversed flap. The flap was used for reconstruction of intra-oral soft tissue defect in 13 patients and composite defects in 8 patients.

Results
Of 21 patients 12 were males and 9 were females, age ranged from 32 to 83 years. The primary tumor sites included buccal mucosa (7), tongue (4), alveolar margin (3), floor of mouth (5) and lip (2). Eventually in this study, we adopted completing the neck dissection first before flap harvest. Complete flap loss occurred in 2 whereas 3 patients had partial flap loss. Follow up ranged from 3 to 44 months, one patient died from metastatic disease. Four patients developed neck recurrences.

Conclusion
The submental flap is a valid option for reconstruction of intra-oral soft tissue as well as composite oral defects particularly in elderly patients. However, oncologically sound neck dissection should be assured.
Ultrasound in the evaluation of enthesitis: status and perspectives
Authors: Gandjbakhch Frédérique , Terslev Lene , Joshua Fredrick , Wakefield Richard J , Naredo Esperanza , D'Agostino Maria Antonietta ,   OMERACT Ultrasound Task Force
Published: December 2011

Abstract

Introduction

An increasing number of studies have applied ultrasound to the evaluation of entheses in spondyloarthritis patients. However, no clear agreement exists on the definition of enthesitis, on the number and choice of entheses to examine and on ultrasound technique, which may all affect the results of the examination. The objectives of this study were to first determine the level of homogeneity in the ultrasound definitions for the principal lesions of enthesitis in the published literature and second, to evaluate the metric properties of ultrasound for detecting enthesitis according to the OMERACT filter.

Methods

Search was performed in PUBMED and EMBASE. Both grey-scale and Doppler definitions of enthesitis, including describing features of enthesitis, were collected and metrological qualities of studies were assessed.

Results

After selection, 48 articles were analyzed. The definition of ultrasound enthesitis and elementary features varied among authors. Grey-scale enthesitis was characterized by increasing thickness (94% of studies), hypoechogenicity (83%), enthesophytes (69%), erosions (67%), calcifications (52%), associated bursitis (46%) and cortical irregularities (29%). Only 46% of studies reported the use of Doppler. High discrepancies were observed on frequency, type of probe and Doppler mode used. Face and content validity were the most frequently evaluated criteria (43%) followed by reliability (29%) and responsiveness (19%).

Conclusions

Ultrasound has evidence to support face, content validity and reliability for the evaluation of enthesitis, though there is a lack of well-reported methodology in most of the studies. Consensus on elementary lesions and standardization of exam is needed to determine the ultrasound definition of enthesitis in grey-scale and in Doppler for future applications.
Constitutive immune function in European starlings,Sturnus vulgaris, is decreased immediately after an endurance flight in a wind tunnel
Authors: Nebel Silke , Bauchinger Ulf , Buehler Deborah M. , Langlois Lillie A. , Boyles Michelle , Gerson Alexander R. , Price Edwin R. , McWilliams Scott R. , Guglielmo Christopher G. 
Published: December 2011

SUMMARYLife-history theory predicts that animals face a trade-off in energy allocation between performing strenuous exercise, such as migratory flight, and mounting an immune response. We experimentally tested this prediction by studying immune function in European starlings, Sturnus vulgaris, flown in a wind tunnel. Specifically, we predicted that constitutive immune function decreases in response to training and, additionally, in response to immediate exercise. We compared constitutive immune function among three groups: (1) ‘untrained’ birds that were kept in cages and were not flown; (2) ‘trained’ birds that received flight training over a 15 day period and performed a 1-4 h continuous flight, after which they rested for 48 h before being sampled; and (3) ‘post-flight’ birds that differed from the ‘trained’ group only in being sampled immediately after the final flight. A bird in our trained group represents an individual during migration that has been resting between migratory flights for at least 2 days. A bird in our post-flight group represents an individual that has just completed a migratory flight and has not yet had time to recover. Three of our four indicators (haptoglobin, agglutination and lysis) showed the predicted decrease in immune function in the post-flight group, and two indicators (haptoglobin, agglutination) showed the predicted decreasing trend from the untrained to trained to post-flight group. Haptoglobin levels were negatively correlated with flight duration. No effect of training or flight was detected on leukocyte profiles. Our results suggest that in European starlings, constitutive immune function is decreased more as a result of immediate exercise than of exercise training. Because of the recent emergence of avian-borne diseases, understanding the trade-offs and challenges faced by long-distance migrants has gained a new level of relevance and urgency.
Total recoil: perch compliance alters jumping performance and kinematics in green anole lizards (Anolis carolinensis)
Authors: Gilman Casey A. , Bartlett Michael D. , Gillis Gary B. , Irschick Duncan J. 
Published: December 2011

SUMMARYJumping is a common form of locomotion for many arboreal animals. Many species of the arboreal lizard genus Anolis occupy habitats in which they must jump to and from unsteady perches, e.g. narrow branches, vines, grass and leaves. Anoles therefore often use compliant perches that could alter jump performance. In this study we conducted a small survey of the compliance of perches used by the arboreal green anole Anolis carolinensis in the wild (N=54 perches) and then, using perches within the range of compliances used by this species, investigated how perch compliance (flexibility) affects the key jumping variables jump distance, takeoff duration, takeoff angle, takeoff speed and landing angle in A. carolinensis in the laboratory (N=11). We observed that lizards lost contact with compliant horizontal perches prior to perch recoil, and increased perch compliance resulted in decreased jump distance and takeoff speed, likely because of the loss of kinetic energy to the flexion of the perch. However, the most striking effect of perch compliance was an unexpected one; perch recoil following takeoff resulted in the lizards being struck on the tail by the perch, even on the narrowest perches. This interaction between the perch and the tail significantly altered body positioning during flight and landing. These results suggest that although the use of compliant perches in the wild is common for this species, jumping from these perches is potentially costly and may affect survival and behavior, particularly in the largest individuals.