bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of clinically symptomatic pneumothorax in ultrasound‐guided infraclavicular and supraclavicular brachial plexus block
Authors: Gauss A. , Tugtekin I. , Georgieff M. , Dinse‐Lambracht A. , Keipke D. , Gorsewski G. 
Published: March 2014

SummaryThe use of periclavicular brachial plexus block as regional anaesthesia for surgical procedures on the upper extremity is common. However, the proximity of the pleura results in a risk of pneumothorax. Without ultrasound monitoring, the pneumothorax risk has been reported to be as high as 6.1%. We conducted a prospective, observational study to examine the risk of pneumothorax in 6366 ultrasound‐guided periclavicular plexus blocks. All patients with a clinically manifest and radiologically confirmed pneumothorax were analysed. Clinically symptomatic pneumothorax occurred in four patients (0.06%; 95% CI 0.001–0.124), in three of them after a two‐day latency period. Ultrasound guidance does therefore appear to reduce the risk of pneumothorax. Although all of the anaesthesiologists involved in the complications had previously performed fewer than 20 blocks, we are not able to confirm that a block experience ≤ 20 is a significant risk factor. Faulty image‐setting, inability to obtain a view of the needle tip and inadequate supervision are likely to be important risk factors.
Ear drainage and the role of sepsis evaluations in the neonatal intensive care unit
Authors: Khattab Mona , Cannon‐Heinrich Charlene , Bizzarro Matthew J. 
Published: March 2014

AbstractAimTo design and implement an intervention to reduce ear drainage and subsequent sepsis evaluation and treatment in the neonatal intensive care unit.MethodsFrom 2008 to 2011, we observed an increase in the rates of ear drainage warranting investigation. Data collection was performed from 1991 to 2013 on 50 cases. Preliminary analysis revealed an association between timing of endotracheal tube tape changes and onset of drainage. We speculated that pooling of anti‐adhesive solution into the external auditory canal was precipitating an inflammatory process. Unit‐wide education was conducted to protect the ears during tape removal. Post‐initiative rates of drainage were collected and compared with pre‐initiative rates.ResultsMedian gestational age and birthweight were 26 weeks and 754 g, respectively. In 64% of cases, an anti‐adhesive solution was used on the face within 48 h of the onset of drainage. Sepsis evaluation was performed in 68% of cases. Rates of ear drainage peaked from 2008 to 2011 at 9.18 per 1000 admissions when a new anti‐adhesive product was used, declining to 0.66 post‐initiative (rate difference: −8.52; 95% CI: −12.00, −5.03).ConclusionProtecting the ear from anti‐adhesive solutions during tape removal may reduce rates of noninfectious ear drainage and limit unnecessary interventions.
An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin
Authors: Carrancio Soraya , Markovics Jennifer , Wong Piu , Leisten Jim , Castiglioni Paola , Groza Matthew C. , Raymon Heather K. , Heise Carla , Daniel Tom , Chopra Rajesh , Sung Victoria 
Published: March 2014

SummarySotatercept (ACE‐011), a recombinant human fusion protein containing the extracellular domain of the human Activin receptor IIA, binds to and inhibits activin and other members of the transforming growth factor ‐β (TGF‐β) superfamily. Administration of sotatercept led to a rapid and sustained increase in red blood cell (RBC) count and haemoglobin (Hb) in healthy volunteers (phase I clinical trials), but the mechanism is not fully understood. Mice treated with RAP‐011 (murine ortholog of ACE‐011) respond with a rapid (within 24 h) increase in haematocrit, Hb, and RBC count. These effects are accompanied by an equally rapid stimulation of late‐stage erythroid precursors in the bone marrow (BM). RAP‐011 also induces a significant increase in erythroid burst‐forming units and erythropoietin, which could contribute to additional, sustained effects on RBC production. Further in vitro co‐culture studies demonstrate that BM accessory cells are required for RAP‐011 effects. To better understand which TGF‐β family ligand(s) mediate RAP‐011 effects, we evaluated the impact of several of these ligands on erythroid differentiation. Our data suggest that RAP‐011 may act to rescue growth differentiation factor 11/Activin A‐induced inhibition of late‐stage erythropoiesis. These data define the mechanism of action of a novel agent that regulates RBC differentiation and provide the rationale to develop sotatercept for the treatment of anaemia and ineffective erythropoiesis.
High‐Throughput Screen of Natural Product Extracts in A Yeast Model of Polyglutamine Proteotoxicity
Authors: Walter Gladis M. , Raveh Avi , Mok Sue‐Ann , McQuade Thomas J. , Arevang Carl J. , Schultz Pamela J. , Smith Matthew C. , Asare Samuel , Cruz Patricia G. , Wisen Susanne , Matainaho Teatulohi , Sherman David H. , Gestwicki Jason E. 
Published: March 2014

Proteins with expanded polyglutamine (polyQ) segments cause a number of fatal neurodegenerative disorders, including Huntington's disease (HD). Previous high‐throughput screens in cellular and biochemical models of HD have revealed compounds that mitigate polyQ aggregation and proteotoxicity, providing insight into the mechanisms of disease and leads for potential therapeutics. However, the structural diversity of natural products has not yet been fully mobilized toward these goals. Here, we have screened a collection of ~11 000 natural product extracts for the ability to recover the slow growth of ΔProQ103‐expressing yeast cells in 384‐well plates (Z' ~ 0.7, CV ~ 8%). This screen identified actinomycin D as a strong inhibitor of polyQ aggregation and proteotoxicity at nanomolar concentrations (~50–500 ng/mL). We found that a low dose of actinomycin D increased the levels of the heat‐shock proteins Hsp104, Hsp70 and Hsp26 and enhanced binding of Hsp70 to the polyQ in yeast. Actinomycin also suppressed aggregation of polyQ in mammalian cells, suggesting a conserved mechanism. These results establish natural products as a rich source of compounds with interesting mechanisms of action against polyQ disorders.
Rational Design and Screening Study of Novel Lead Compound Based on Acetohydroxyacid Synthase Structure
Authors: Jin Jingnan , Qi Xiaojuan , Yao Dandan , Mao Bangqiang , Li Jianhong , Zhang Qingye , Chen Changshui 
Published: March 2014

Acetohydroxyacid synthase (AHAS) is a key target and has extensive application in the process of herbicide discovery. However, the problem of weed resistance is gradually serious with long‐term excessive use of commercial AHAS‐inhibiting herbicides, and so, it is urgent to develop novel herbicides. In this study, a virtual screening was performed based on the active site of AHAS. Then, the hit‐10 compound with the IC50 value of 47.41 mg/L was selected as lead compound based on the biological testing. Subsequently, the optimization design and syntheses of lead compound were carried out according to the analyzing results of mechanism and receptor‐/ligand‐binding mode. Three novel 5‐substituted benzyl‐1,3,4‐thiadiazol‐2‐carbamic acid phenyl ester derivatives were designed and synthesized. Bioactive assay results of the three target compounds showed that all of them displayed the higher inhibition than lead compound to AHAS, with the IC50 values in the 23.54–32.05 mg/L range, and the inhibition rates were increased by 30–50%. Finally, we also analyzed the possible inhibitory mechanism of the three target compounds based on the molecular docking between AHAS and target compounds. This study would provide a novel chemical structure for the discovery of novel AHAS herbicides.
Developmental regulation of p53-dependent radiation-induced thymocyte apoptosis in mice
Authors: Gentil Dit Maurin A , Lemercier C , Collin-Faure V , Marche P N , Jouvin-Marche E , Candéias S M 
Published: March 2014

SummaryThe production of T cell receptor αβ+ (TCRαβ+) T lymphocytes in the thymus is a tightly regulated process that can be monitored by the regulated expression of several surface molecules, including CD4, CD8, cKit, CD25 and the TCR itself, after TCR genes have been assembled from discrete V, D (for TCR-β) and J gene segments by a site-directed genetic recombination. Thymocyte differentiation is the result of a delicate balance between cell death and survival: developing thymocytes die unless they receive a positive signal to proceed to the next stage. This equilibrium is altered in response to various physiological or physical stresses such as ionizing radiation, which induces a massive p53-dependent apoptosis of CD4+CD8+ double-positive (DP) thymocytes. Interestingly, these cells are actively rearranging their TCR-α chain genes. To unravel an eventual link between V(D)J recombination activity and thymocyte radio-sensitivity, we analysed the dynamics of thymocyte apoptosis and regeneration following exposure of wild-type and p53-deficient mice to different doses of γ-radiation. p53-dependent radio-sensitivity was already found to be high in immature CD4−CD8− (double-negative, DN) cKit+CD25+ thymocytes, where TCR-β gene rearrangement is initiated. However, TCR-αβ−CD8+ immature single-positive thymocytes, an actively cycling intermediate population between the DN and DP stages, are the most radio-sensitive cells in the thymus, even though their apoptosis is only partially p53-dependent. Within the DP population, TCR-αβ+ thymocytes that completed TCR-α gene recombination are more radio-resistant than their TCR-αβ− progenitors. Finally, we found no correlation between p53 activation and thymocyte sensitivity to radiation-induced apoptosis.
Object Concepts in the Chemical Senses
Authors: Stevenson Richard J. 
Published: March 2014

AbstractThis paper examines the applicability of the object concept to the chemical senses, by evaluating them against a set of criteria for object‐hood. Taste and chemesthesis do not generate objects. Their parts, perceptible from birth, never combine. Orthonasal olfaction (sniffing) presents a strong case for generating objects. Odorants have many parts yet they are perceived as wholes, this process is based on learning, and there is figure‐ground segregation. While flavors are multimodal representations bound together by learning, there is no functional need for flavor objects in the mouth. Rather, food identification occurs prior to ingestion using the eye and nose, with the latter retrieving multimodal flavor objects via sniffing (e.g.,sweetsmelling caramel). While there are differences in object perception between vision, audition, and orthonasal olfaction, the commonalities suggest that the brain has adopted the same basic solution when faced with extracting meaning from complex stimulus arrays.
Association between vascular access type and patient mortality among elderly patients on hemodialysis in Canada
Authors: Zhang Joyce C. , Al‐Jaishi Ahmed A. , Na Yingbo , de Sa Eric , Moist Louise M. 
Published: March 2014

AbstractOptimal vascular access in elderly patients requires consideration of the benefits and risks in a population with increased comorbidity and mortality. Our objective was to examine the association between vascular access type and patient mortality by age category among incident adult hemodialysis patients registered in the Canadian Organ Replacement Register between 2001 and 2010. We also describe the secular trend in incident and prevalent vascular access use. We used a Cox proportional hazards model to evaluate the overall mortality in patients aged less than 65, 65–74, 75–85, and greater than 85 years who initiated hemodialysis using a central venous catheter (catheter) or arteriovenous (AV)‐access (fistula or graft) using an intention‐to‐treat approach. The cohort of 39,721 patients consisted of 42%, 27%, 26%, and 5% of patients aged <65, 65–74, 75–85, and >85, respectively. Patients who initiated hemodialysis using an AV‐access constituted 21%, 22%, 20%, and 15% of each age category. AV access use was associated with lower adjusted mortality compared with catheter use in each age category (Hazard Ratios [HR], 0.67; 95% Confidence Interval [0.62–0.72]; HR, 0.76 [0.63–0.91]; HR, 0.77 [0.64–0.93], HR, 0.73 [0.56–0.96], respectively). In Canada, use of an AV‐access is associated with lower mortality across all age categories, even in the very elderly. Further studies are required to understand the patient preference, complications, and resource use when selecting access type in the elderly.
Chat-based telepharmacy in Denmark: design and early results
Authors: Ho Inger , Nielsen Line , Jacobsgaard Helle , Salmasi Hassan , Pottegård Anton 
Published: March 2014

Abstract

Objectives
Following the introduction of a nationwide online telepharmacy chat-service in Denmark in the spring of 2012, offering free counselling to all Danish citizens, we aimed to investigate the types of enquiries that are made to the telepharmacy.

Methods
We extracted 500 consecutive chat transcripts and categorised them in four categories: drug-related, symptom, technical and other. These categories were further divided into 28 prespecified subcategories. After the categorisation of the 500 transcripts, 7 new subcategories were added and the material was reanalysed. For drug-related enquiries, the drug in question was registered according to the anatomical-therapeutic-chemical system developed by World Health Organization. Veterinary and empty (nonresponding) enquiries were excluded.

Key findings
Four hundred seventy-six eligible enquiries were identified and categorised. The enquiries were found to be diverse: 170 enquiries (35.7%) were drug-related, 124 (26.1%) were technical in nature, 91 (19.1%) were related to symptoms and 91 (19.1%) of the enquiries were categorised as other. The most common drug class was ‘drugs related to the genitourinary system and sex hormones’. Only 50 (10.5%) of the enquiries happened in connection with an actual purchase at the online pharmacy. Of all enquiries, 28.6% led to a referral to a medical doctor. Of the customers, 89.2% were satisfied with the online counselling.

Conclusion
The diverse enquiries require professional chat operators with broad experience. Some subjects are overrepresented when compared with regular pharmacy counselling and should receive special attention. Continued monitoring is considered essential.
When Should Physical Rehabilitation Commence after Stroke: A Systematic Review
Authors: Lynch Elizabeth , Hillier Susan , Cadilhac Dominique 
Published: March 2014

Background Knowing when to commence physical rehabilitation after stroke is important to ensure optimal benefit for stroke survivors and efficient health care. The aims of this review were to: determine the effects on mortality, function and complications when physical rehabilitation commences ‘early’ (within seven days of stroke); and describe the effects of early transfer to rehabilitation wards/hospitals when sustained rehabilitation is unavailable in acute stroke units. Review summary From 3751 potential articles we included 5 randomized controlled trials and 38 cohort studies. Meta-analysis was performed with 3 randomized controlled trials involving 159 people to investigate the effects of commencing physical rehabilitation within 24 h of stroke compared to 48 h. Commencing physical rehabilitation within 24 h trended towards greater mortality (Mantel-Haenszel odds ratio 2·58; 95% confidence interval 0·98 to 6·79, P = 0·06), with no differences in complications or health outcomes. The cohort studies provided evidence of benefits when physical rehabilitation was commenced on the day of admission ( n = 1), within 3 days of stroke ( n = 3), or ‘sooner rather than later’ (3 of 4 studies). The effect of earlier transfer to rehabilitation was reported in 32 cohort studies. In 23/26 (88%) cohort studies that accounted for age and stroke severity, results favored earlier transfer for improving post-stroke function, with no consensus on timeframes. Conclusion In summary, the benefits of commencing physical rehabilitation within 24 h of stroke remain unclear from the current literature. Commencing physical rehabilitation or transferring to rehabilitation services ‘early’ may provide better functional outcomes.
Differences in Ischemic and Hemorrhagic Recurrence Rates among Race-Ethnic Groups in the PRoFESS Secondary Stroke Prevention Trial
Authors: Estol Conrado J. , Bath Philip M. W. , Gorelick Philip B. , Cotton Daniel , Martin Renee Hebert ,   PRoFESS Publications Committee and PRoFESS Investigators
Published: March 2014

Background and Aims Epidemiological studies show that vascular risk factors are the same across the world but their effect vary between different race-ethnic groups. However, few studies have evaluated differences in recurrent stroke rates in various race-ethnicities. In >20 000 patients spanning 35 countries encompassing most race-ethnicities, we evaluated the incidence of ischemic and hemorrhagic strokes and myocardial infarction in patients within the context of the largest secondary stroke prevention trial (Prevention Regimen for Effectively Avoiding Secondary Strokes) to identify any significant differences. Methods There were 20 332 patients with a recent ischemic stroke randomized in a factorial design to receive the antiplatelet agent clopidogrel vs. aspirin plus extended-release dipyridamole, and 80 mg of the anthypertensive telmisartan vs. placebo. The primary outcome for the trial was the time to any recurrent stroke. Statistical analysis was used to detect race-ethnic differences in recurrent vascular events. Results Mean patient age was 66 (±8·6) years and 36% were women. The study included 58% European/Caucasian, 33% Asians, 5% Latin/Hispanic, and 4% Black African. There were 74% of patients that were hypertensive, and average systolic and diastolic blood pressure was 144·1/83·8 mmHg. There was at least one significant difference in the overall test of all race-ethnic groups in myocardial infarction and symptomatic intracerebral hemorrhage occurrence. In the Kaplan–Meier hemorrhage and stroke-free survival curves, Asians showed a significantly higher recurrence of ischemic stroke risk in the 135–150 mmHg and greater than 150 mm Hg blood pressure groups, and a greater risk of hemorrhage recurrence in the greater than 150 mmHg blood pressure group. Conclusions We found a significant difference in myocardial infarction and symptomatic intracerebral hemorrhage recurrence among different race-ethnic groups. The risk of recurrent ischemic and hemorrhagic stroke was greater in Asians with high blood pressure.
Current approaches to fine mapping of antigen–antibody interactions
Authors: Abbott W. Mark , Damschroder Melissa M. , Lowe David C. 
Published: March 2014

SummaryA number of different methods are commonly used to map the fine details of the interaction between an antigen and an antibody. Undoubtedly the method that is now most commonly used to give details at the level of individual amino acids and atoms is X‐ray crystallography. The feasibility of undertaking crystallographic studies has increased over recent years through the introduction of automation, miniaturization and high throughput processes. However, this still requires a high level of sophistication and expense and cannot be used when the antigen is not amenable to crystallization. Nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA‐based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids. It is quite common to use more than one method because of the limitations and even with a crystal structure it can be useful to use mutagenesis to tease apart the contribution of individual amino acids to binding affinity.
IMF Conditionality and the Intertemporal Allocation of Resources
Authors: Naqvi Hassan 
Published: March 2014

AbstractThis article analyzes the impact of IMF (International Monetary Fund) conditionality on the intertemporal allocation of resources in an emerging market economy. The study identifies a principal‐agent problem between the government of the emerging market and its citizens and shows that conditionality has the potential to mitigate the resulting misallocation of resources. Nevertheless, the analysis indicates that if IMF lending were influenced by geopolitical motives then the suboptimal allocation of resources would remain notwithstanding IMF conditionality.
Extending social security coverage to the rural sector in China
Authors: Chen Tianhong , Turner John A. 
Published: March 2014

AbstractIn late 2009 China launched an innovative, voluntary programme that by 2011 had extended pension coverage to 326.4 million people in the rural sector, including contributors and beneficiaries. It requires one contribution per year and provides a flat‐rate benefit and a contributions‐related benefit through a contributory individual account, with a government guarantee that the benefit will continue for life. The programme encourages participation of persons who do not pay income taxes, and thus have no tax incentive to participate, by providing substantial government subsidies. As a further incentive, old‐age benefits are provided to older parents when all their adult children participate in the contributory programme.
Response of the Human Neurogenic Bladder to KCl, Carbachol, ATP and CaCl2
Authors: SAITO M. , KONDO A. , KATO T. , HASEGAWA S. , MIYAKE K. 
Published: March 2014

Summary— The in vitro pharmacological responses of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2 have been analysed.The contractility (contractile strength and ED50) of neurogenic bladders was significantly increased when treated with carbachol, ATP and CaCl2. In contrast, there was no apparent difference in the responsiveness of neurogenic bladders when treated with KCl.There was no apparent correlation between pharmacological responsiveness and clinical parameters, such as gender, age or cystometric data, in the neurogenic bladders.