bluuebunny/crossref_metadata_2025_split huggingface dataset:
Escherichia coli surface display for the selection of nanobodies
Authors: Salema Valencio , Fernández Luis Ángel 
Published: August 2017

SummaryNanobodies (Nbs) are the smallest functional antibody fragments known in nature and have multiple applications in biomedicine or environmental monitoring. Nbs are derived from the variable segment of camelid heavy chain‐only antibodies, known as VHH. For selection, libraries of VHH gene segments from naïve, immunized animals or of synthetic origin have been traditionally cloned in E. coli phage display or yeast display systems, and clones binding the target antigen recovered, usually from plastic surfaces with the immobilized antigen (phage display) or using fluorescence‐activated cell sorting (FACS; yeast display). This review briefly describes these conventional approaches and focuses on the distinct properties of an E. coli display system developed in our laboratory, which combines the benefits of both phage display and yeast display systems. We demonstrate that E. coli display using an N‐terminal domain of intimin is an effective platform for the surface display of VHH libraries enabling selection of high‐affinity Nbs by magnetic cell sorting and direct selection on live mammalian cells displaying the target antigen on their surface. Flow cytometry analysis of E. coli bacteria displaying the Nbs on their surface allows monitoring of the selection process, facilitates screening, characterization of antigen‐binding clones, specificity, ligand competition and estimation of the equilibrium dissociation constant (KD).
Patient and Surrogate Views of Community Consultation for Emergency Research
Authors: Fehr Alexandra E. , Scicluna Victoria M. , Pentz Rebecca D. , Haggins Adrianne N. , Dickert Neal W. 
Published: July 2017

AbstractObjectivePretrial community consultation (CC) is required for emergency research conducted under an exception from informed consent (EFIC) in the United States. CC remains controversial and challenging, and minimal data exist regarding the views of individuals enrolled in EFIC trials on this process. It is important to know whether participants perceive CC to be meaningful and, if so, whom they believe should be consulted.MethodsWe conducted a secondary analysis of data from two studies interviewing patients and surrogates of two recent EFIC trials (PEER‐RAMPART and PEER‐ProTECT). These interviews included similar open‐ and closed‐ended questions regarding participants' views of the importance of CC, the rationale for their responses, and their views regarding which populations should be included in consultation efforts. A template analytic strategy was used for qualitative analysis of textual data, and descriptive statistics were tabulated to characterize demographic data and instances of major themes.ResultsNinety percent of participants perceived CC to be valuable. Participants' reasons for finding CC valuable clustered in two categories: 1) as a method of informing the public about the trial to be conducted and 2) as a way of obtaining input and feedback from the community. Participants cited the medical community (43%) and individuals with a connection to the study condition (41%) as the most important groups to involve in consultation efforts; only 5% suggested consulting the general public in the area where the research will be conducted.ConclusionParticipants in EFIC trials and their decision makers generally valued CC as a method of informing and seeking input from the community. Participants felt that the most appropriate groups to consult were the medical community and individuals with connections to the condition under study. Consultation efforts focused on these two groups, rather than the general public, may be more efficient and more meaningful to individuals involved in EFIC trials. These findings also reinforce the importance of the distinction between public disclosure and CC.
Performance of the Hack's Impairment Index Score: A Novel Tool to Assess Impairment from Alcohol in Emergency Department Patients
Authors: Hack Jason B. , Goldlust Eric J. , Ferrante Dennis , Zink Brian J. 
Published: July 2017

AbstractBackgroundOver 35 million alcohol‐impaired (AI) patients are cared for in emergency departments (EDs) annually. Emergency physicians are charged with ensuring AI patients’ safety by identifying resolution of alcohol‐induced impairment. The most common standard evaluation is an extemporized clinical examination, as ethanol levels are not reliable or predictive of clinical symptoms. There is no standard assessment of ED AI patients.ObjectiveThe objective was to evaluate a novel standardized ED assessment of alcohol impairment, Hack's Impairment Index (HII score), in a busy urban ED.MethodsA retrospective chart review was performed for all AI patients seen in our busy urban ED over 24 months. Trained nurses evaluated AI patients with both “usual” and HII score every 2 hours. Patients were stratified by frequency of visits for AI during this time: high (≥ 6), medium (2–5), and low (1). Within each category, comparisons were made between HII scores, measured ethanol levels, and usual nursing assessment of AI. Changes in HII scores over time were also evaluated.ResultsA total of 8,074 visits from 3,219 unique patients were eligible for study, including 7,973 (98.7%) with ethanol levels, 5,061 (62.7%) with complete HII scores, and 3,646 (45.2%) with health care provider assessments. Correlations between HII scores and ethanol levels were poor (Pearson's R2 = 0.09, 0.09, and 0.17 for high‐, medium‐, and low‐frequency strata). HII scores were excellent at discriminating nursing assessment of AI, while ethanol levels were less effective. Omitting extrema, HII scores fell consistently an average 0.062 points per hour, throughout patients’ visits.ConclusionsThe HII score applied a quantitative, objective assessment of alcohol impairment. HII scores were superior to ethanol levels as an objective clinical measure of impairment. The HII declines in a reasonably predictable manner over time, with serial evaluations corresponding well with health care provider evaluations.
Intrauterine delivery of subunit vaccines induces a systemic and mucosal immune response in rabbits
Authors: Pasternak Jonathan Alexander , Hamonic Glenn , Forsberg Nikki M. , Wheler Colette L. , Dyck Michael K. , Wilson Heather L. 
Published: August 2017

ProblemMucosal vaccines have long been sought after to improve protection though the production of both a mucosal and systemic immune response, and are thought to be particularly effective at the site of induction. Development of such vaccines has, however, been delayed by the general propensity to develop immune tolerance to antigens encountered at mucosal sites. This study aimed to determine whether an appropriately formulated subunit vaccine delivered to the uterine lumen would effectively trigger induction of immunity over tolerance.MethodsOvalbumin (OVA), truncated glycoprotein D (tGD) from bovine herpesvirus, and a fusion protein of porcine parvovirus VP2 and bacterial thioredoxin (rVP2‐TrX) were each formulated with a tri‐adjuvant combination of Poly(I : C) (PIC), a host defense peptide (HDP), and a polyphosphazene (PCEP). A single dose of vaccine was delivered either intramuscularly (IM) or into the uterine lumen of intact female rabbits, and the humoral response subsequently evaluated both systemically and at local and distal mucosal sites.ResultsVaccination through either route‐induced antigen‐specific humoral responses systemically and within the local (uterus) and distal mucosa (lungs and vagina). The observed mucosal response was not compartmentalized to, or within, the upper genital tract and the degree of response appeared to be at least in part antigen dependant.ConclusionThe results of this study provide proof of principle that the uterus can be used as an induction site for subunit vaccination and that vaccine formulation with appropriate adjuvants can trigger both systemic and mucosal immunity when administered IM or into the uterine lumen.
Vitamin D deficiency in an Italian cohort of infertile women
Authors: Triggianese Paola , Watad Abdulla , Cedola Francesca , Perricone Carlo , Amital Howard , Giambini Ilio , Perricone Roberto , Shoenfeld Yehuda , De Carolis Caterina 
Published: August 2017

ProblemThe purpose of this study was to explore whether vitamin D might be a marker of female primary infertility in association with the presence of autoimmune diseases (ADs).MethodsThe study was a cross‐sectional descriptive study in consecutive outpatients of the Polymedical Center for Prevention of Recurrent Spontaneous Abortion (RSA), in Rome, Italy. Women were eligible if they received a diagnosis of primary infertility or RSA. Serum vitamin D, calcium, and PTH were analyzed.ResultsWomen with primary infertility (n=70) or RSA/non‐infertile (n=105) were enrolled; controls (n=250) were included. Infertile women presented lower vitamin D (P=0.03) and higher prevalence of AD (P=0.007) than non‐infertile women. In the multivariate analysis, the presence of ADs is associated with higher odds of infertility (OR=2.2), while normal vitamin D was a protective factor (OR=0.9).ConclusionWe described that having vitamin D deficiency and suffering from an AD are independent risk factors for women primary infertility. Supplementation of vitamin D might be useful for pregnancy outcome.
Assessment of eosinophilic airway inflammation as a contribution to the diagnosis of occupational asthma
Authors: Beretta C. , Rifflart C. , Evrard G. , Jamart J. , Thimpont J. , Vandenplas O. 
Published: August 2017

AbstractBackgroundAscertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC).MethodsThe study included 240 consecutive subjects with a suspicion of OA who completed a SIC, of whom 133 showed a positive response. The sensitivity, specificity, and predictive values of NSBH, and FeNO, as well as sputum eosinophil counts assessed at baseline of the SIC were determined.ResultsA concentration of histamine inducing a 20% decline in FEV1 (PC20) ≤16 mg/mL showed a sensitivity of 87% and a specificity of 36%. A FeNO level ≥25 ppb and a sputum eosinophil count ≥2% provided lower sensitivity rates (47% and 39%, respectively) than the PC20 value. Eight of the 17 subjects without baseline NSBH despite a positive SIC showed a sputum eosinophil count ≥2%, a FeNO level ≥25 ppb, or both outcomes. Combining either a PC20 value ≤16 mg/mL or a FeNO ≥25 ppb increased the sensitivity to 91%. Using either a PC20 ≤16 mg/mL or a sputum eosinophil count ≥1% increased the sensitivity to 94%.ConclusionAdding the assessment of FeNO level and sputum eosinophils to NSBH improves the identification of subjects who may have OA and require further objective testing before excluding the possibility of OA.
Stroke risk among adult patients with third, fourth or sixth cranial nerve palsy: a Nationwide Cohort Study
Authors: Rim Tyler Hyungtaek , Han Jinu , Choi Yoon Seong , Lee Taekjune , Kim Sung Soo 
Published: August 2017

AbstractPurposeThis study sought to determine whether isolated third, fourth and sixth cranial nerve palsies (NPs) are associated with increased short‐ and long‐term risk of a subsequent stroke.MethodsThis was a nationwide retrospective propensity score‐matched cohort study. A cohort of patients with NP (n = 466) and a randomly selected, propensity‐matched control cohort (n = 2281) were extracted from the Korean national insurance claim database. Subjects were tracked for 5 years total, subdivided into periods of 0–1 years, 1–3 years and 3–5 years. We assessed the risk of stroke using hazard ratios (HRs) and confidence intervals (CIs) after adjustments using Cox regression at different time intervals.ResultsThe median follow‐up was 3.1 years. Stroke developed in 18.9% of the NP cohort and 7.5% of the control cohort. Stroke risk after NP was highest in the first year [14.7 per 100 person‐year at 0–1 years (HR = 6.6), 3.1 per 100 person‐year at 1–3 years (HR = 1.6) and 4.3 per 100 person‐year at 3–5 years (HR = 2.8)]. Each type of NP was also associated with stroke risk: within 0–1 years, stroke risk was increased in third (HR = 7.6), fourth (HR = 6.0) and sixth (HR = 5. 84) NPs. In the 3‐ to 5‐year period, risk was increased in sixth (HR = 4.7) and fourth (HR = 3.3) NPs, but not third (HR = 0.6) NPs.ConclusionPatients in the NP cohort were more likely to have a stroke than those in the matched control cohort; the increased risk was both time‐ and cranial nerve‐dependent.
Von Helmholtz's ophthalmometer: historical review and experience with one of the last surviving original devices
Authors: Godefrooij Daniel A. , Galvis Virgilio , Tello Alejandro 
Published: August 2017

AbstractHermann von Helmholtz (1821–1894) was one of the most important scientists of the nineteenth century in optics and ophthalmology. One of his significant contributions in the field of vision sciences was the invention of the ophthalmometer in 1850, which was the precursor of the keratometers still used in clinical practice today. However, this development tends to be little recognized, and to be overshadowed by others of the achievements of this singular scientist. This review describes the historical setting behind the von Helmholtz's ophthalmometer and its mechanism. We also describe the modifications that were later made to the design. We report on our experience measuring a living human cornea with one of the last surviving devices in the world. The ophthalmometer by von Helmholtz marked the beginning of an era in the ophthalmology of the late nineteenth century, and although its original design was not broadly used in the clinical practice, and later abandoned, it opened the way for the development of practical systems very similar to the ones that we use even today.
Ultrawide field scanning laser ophthalmoscopy imaging of lipemia retinalis
Authors: Silva Paolo S. , Gupta Aditi , Ajlan Radwan S. , Schlossman Deborah K. , Tolson Ann M. , Cavallerano Jerry D. , Aiello Lloyd Paul 
Published: August 2017

AbstractObjectiveTo describe the characteristic retinal features of lipemia retinalis when using ultrawide field scanning laser ophthalmoscopy.Main PointsWe report a case series of three subjects with ultrawide field retinal images showing cream discoloration of the fundus, light salmon‐coloured posterior retinal vessels and greyish pink peripheral vasculature. On green‐only imaging, many of the vessels appear light rather than typically dark.ConclusionLipemia retinalis is readily apparent on ultrawide field imaging and illustrates the alterations that systemic diseases may induce in the posterior and peripheral retinal vasculature. Ultrawide field imaging highlights the disparate vascular appearance of the posterior pole and retinal periphery in this condition.
The effects of antioxidants on ocular blood flow in patients with glaucoma
Authors: Harris Alon , Gross Josh , Moore Nicholas , Do Thai , Huang Amelia , Gama Willy , Siesky Brent 
Published: August 2017

AbstractPurposeTo investigate the effects of an antioxidant dietary supplement that includes Ginkgo biloba, on retinal and retrobulbar blood flow in patients with open‐angle glaucoma (OAG).MethodsForty‐five patients with confirmed OAG were enroled in a randomized, double blinded, placebo‐controlled cross‐over study. Baseline and postadministration measurements of intraocular pressure (IOP), ocular perfusion pressure (OPP), retrobulbar blood flow, and retinal capillary blood flow were non‐invasively measured (ultrasound and laser Doppler modalities, respectively) before and one month after antioxidant nutraceuticals and placebo administration. Changes in measurements between the active supplement and placebo arms were evaluated using paired t‐tests, with p < 0.05 considered statistically significant.ResultsAntioxidant supplementation produced a statistically significant increase in peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels compared to placebo. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries following antioxidant administration. Additionally, antioxidant supplementation increased superior and inferior temporal retinal capillary mean blood flow and the ratio of active to non‐active retina capillaries compared to placebo.ConclusionOne‐month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds in patients with OAG.
Prophylactic intravitreal antibiotics reduce the risk of post‐traumatic endophthalmitis after repair of open globe injuries
Authors: Abouammoh Marwan A. , Al‐Mousa Abdullah , Gogandi Mohammad , Al‐Mezaine Hani , Osman Essam , Alsharidah Abdulrahman M. , Al‐Kharashi Abdullah , Abu El‐Asrar Ahmed M. 
Published: August 2017

AbstractPurposeTo investigate efficacy of prophylactic intravitreal antibiotics in reducing incidence of endophthalmitis after repair of open globe injuries. At King Abdulaziz University Hospital, a standard protocol of intravenous vancomycin and ceftazidime was used in all cases.MethodsCharts of 353 patients who presented between January 2010 and January 2014 with open globe injury were retrospectively reviewed. In addition, the standard protocol in this cohort included prophylactic intravitreal antibiotics in high‐risk cases at time of primary repair. High‐risk cases were identified based on the presence of one or more of the following risk factors: dirty wound, retained intra‐ocular foreign body (IOFB), rural setting, delayed primary repair of >24 hr and ruptured lens capsule. Rate of endophthalmitis in this recent cohort was compared with that of a previous cohort admitted for primary repair between May 1996 and May 2008 (641 patients). In the previous cohort, protocol did not include prophylactic intravitreal antibiotics.ResultsRates of clinically suspected endophthalmitis and culture‐positive endophthalmitis were higher in previous cohort (24 of 641 eyes; 3.7% and 12 of 641 eyes; 1.9%, respectively) compared to recent cohort (six of 353 eyes; 1.7% and two of 353 eyes; 0.6%, respectively). In high‐risk groups, rates of suspected endophthalmitis and culture‐positive endophthalmitis were higher in previous cohort (19 of 345 eyes; 5.5% and 12 of 345 eyes; 3.5%, respectively) compared to the recent cohort (five of 200 eyes; 2.5% and two of 200 eyes; 1.0%, respectively).ConclusionProphylactic intravitreal antibiotics reduce risk of endophthalmitis after repair of open globe injuries.
Overexpression of integrin α11 induces cardiac fibrosis in mice
Authors: Romaine A. , Sørensen I. W. , Zeltz C. , Lu N. , Erusappan P. M. , Melleby A. O. , Zhang L. , Bendiksen B. , Robinson E. L. , Aronsen J. M. , Herum K. M. , Danielsen H. E. , Sjaastad I. , Christensen G. , Gullberg D. 
Published: August 2017

AbstractAimTo understand the role of the collagen‐binding integrin α11 in vivo, we have used a classical approach of creating a mouse strain overexpressing integrin α11. A transgenic mouse strain overexpressing α11 in muscle tissues was analysed in the current study with special reference to the heart tissue.MethodsWe generated and phenotyped integrin α11 transgenic (TG) mice by echocardiography, magnetic resonance imaging and histology. Wild‐type (WT) mice were subjected to aortic banding (AB) and the expression of integrin α11 was measured in flow cytometry‐sorted cardiomyocytes and non‐myocytes.ResultsTG mice developed left ventricular concentric hypertrophy by 6 months, with increased collagen deposition and reactivation of mRNA encoding foetal genes associated with cardiovascular pathological remodelling compared to WT mice. Masson's trichrome staining revealed interstitial fibrosis, confirmed additionally by magnetic resonance imaging and was found to be most prominent in the cardiac septum of TG but not WT mice. TG hearts expressed increased levels of transforming growth factor‐β2 and transforming growth factor‐β3 and upregulated smooth muscle actin. Macrophage infiltration coincided with increased NF‐κB signalling in TG but not WT hearts. Integrin α11 expression was increased in both cardiomyocytes and non‐myocyte cells from WT AB hearts compared to sham‐operated animals.ConclusionWe report for the first time that overexpression of integrin α11 induces cardiac fibrosis and left ventricular hypertrophy. This is a result of changes in intracellular hypertrophic signalling and secretion of soluble factors that increase collagen production in the heart.
Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children
Authors: Rodrigues Christelle , Chiron Catherine , Rey Elisabeth , Dulac Olivier , Comets Emmanuelle , Pons Gérard , Jullien Vincent 
Published: August 2017

AimsOxcarbazepine is an antiepileptic drug with an activity mostly due to its monohydroxy derivative metabolite (MHD). A parent‐metabolite population pharmacokinetic model in children was developed to evaluate the consistency between the recommended paediatric doses and the reference range for trough concentration (Ctrough) of MHD (3–35 mg l–1).MethodsA total of 279 plasma samples were obtained from 31 epileptic children (age 2–12 years) after a single dose of oxcarbazepine. Concentration‐time data were analysed with Monolix 4.3.2. The probability to obtain Ctrough between 3–35 mg l–1 was determined by Monte Carlo simulations for doses ranging from 10 to 90 mg kg–1 day–1.ResultsA parent‐metabolite model with two compartments for oxcarbazepine and one compartment for MHD best described the data. Typical values for oxcarbazepine clearance, central and peripheral distribution volume and distribution clearance were 140 l h–1 70 kg–1, 337 l 70 kg–1, 60.7 l and 62.5 l h–1, respectively. Typical values for MHD clearance and distribution volume were 4.11 l h–1 70 kg–1 and 54.8 l 70 kg–1 respectively. Clearances and distribution volumes of oxcarbazepine and MHD were related to body weight via empirical allometric models. Enzyme‐inducing antiepileptic drugs (EIAEDs) increased MHD clearance by 29.3%. Fifty‐kg children without EIAEDs may need 20–30 mg kg–1 day–1 instead of the recommended target maintenance dose (30–45 mg kg–1 day–1) to obtain Ctrough within the reference range. By contrast, 10‐kg children with EIAEDs would need 90 mg kg–1 day–1 instead of the maximum recommended dose of 60 mg kg–1 day–1.ConclusionThis population pharmacokinetic model of oxcarbazepine supports current dose recommendations, except for 10‐kg children with concomitant EIAEDs and 50‐kg children without EIAEDs.