bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open‐label clinical trial
Authors: Leroux S. , Jacqz‐Aigrain E. , Elie V. , Legrand F. , Barin‐Le Guellec C. , Aurich B. , Biran V. , Dusang B. , Goudjil S. , Coopman S. , Garcia Sanchez R. , Zhao W. , Manzoni P. ,   on behalf of the FP7 TINN (Treat Infections in NeoNates) consortium
Published: May 2018

AimsThe pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis.MethodsNeonates were randomized 1:1 to fluconazole (loading dose 25 mg kg–1; maintenance dose 12 mg kg–1 day–1 or 20 mg kg–1 day–1, respectively, for infants <30 weeks or ≥30 weeks’ corrected gestational age) or micafungin (loading dose 15 mg kg–1 day–1; maintenance dose 10 mg kg–1 day–1). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks’ corrected gestational age or hospital discharge.ResultsThirty‐six neonates were enrolled. The median (range) gestational age was 28.2 (24.1–40.1) and 26.8 (23.5–40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h–1 kg–1) and volume of distribution (l kg–1) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported.ConclusionBased on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration–time curve target attainment rate in neonates.
Impact of serum 25‐OH vitamin D level on lower urinary tract symptoms in men: a step towards reducing overactive bladder
Authors: Yoo Sangjun , Oh Sohee , Kim Hyung Suk , Choi Han Seok , Park Juhyun , Cho Sung Yong , Son Hwancheol , Jeong Hyeon , Lee Hae Won , Cho Min Chul 
Published: May 2018

ObjectivesTo evaluate the impact of serum vitamin D level on male lower urinary tract symptoms (LUTS).Patients and MethodsMen with LUTS who visited the outpatient clinic of the urology department at one of two hospitals between March 2014 and April 2017 were eligible for inclusion in the study. The impact of vitamin D on LUTS was evaluated using multivariate analysis to adjust for age, body mass index, prostate‐specific antigen, testosterone, glycated haemoglobin, physical activity and prostate volume. To exclude the effect of seasons, we also analysed the impact during each season.ResultsVitamin D level was lowest in winter. According to the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS), the severity of LUTS peaked in winter. There were no seasonal differences between prostate volume, maximum urinary flow rate (Qmax) and post‐void residual urine volume (PVR). For all patients, multivariate analysis showed that lower vitamin D level was significantly associated with higher total OABSS, whereas it was not associated with prostate volume, Qmax, PVR or total IPSS. In winter, lower vitamin D level was significantly associated with higher total OABSS based on multivariate analysis, whereas it was not during other seasons. In patients with vitamin D deficiency, the total OABSS significantly decreased after vitamin D replacement. The greatest improvement in total OABSS was associated with lower pre‐treatment total OABSS and higher post‐treatment vitamin D level.ConclusionsVitamin D deficiency in men with LUTS may play a role in aggravated overactive bladder (OAB) symptoms, especially in winter. Increasing vitamin D level in patients with vitamin D deficiency appears to alleviate OAB symptoms.
IgE sensitization to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma
Authors: Patelis A. , Alving K. , Middelveld R. , James A. , Ono J. , Ohta S. , Izuhara K. , Borres M. P. , Forsberg B. , Janson C. , Malinovschi A. 
Published: May 2018

SummaryBackgroundWe have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle‐aged adults and in young subjects with asthma.ObjectiveTo investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics.MethodsFeNO, urinary eosinophil‐derived neurotoxin (U‐EDN), serum eosinophil cationic protein (S‐ECP) and periostin were measured in 396 asthmatics, aged 17‐76 years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitization to food allergens with measurement of specific IgE (≥0.35 kU/L).ResultsAsthmatics sensitized to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs 16.1 ppb (14.2, 18.2) (P = .005), S‐ECP, 17.7 mg/L (14.8, 21.1) vs 12.8 mg/L (10.9, 14.9) (P = .01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P = .003), than non‐sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P = .01). Sensitization to food allergens related independently to FeNO (P = .02), S‐ECP (P = .006) and periostin (P = .004), whereas sensitization only to airborne allergens related only to FeNO (P = .02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S‐ECP (r = .17, P < .001), periostin (r = .19, P < .001) and U‐EDN (0.16, P < .001). S‐ECP also correlated weakly with U‐EDN (r = .12, P = .02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant.Conclusions & Clinical RelevanceSensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S‐ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management.
Ecology shapes the evolutionary trade‐off between predator avoidance and defence in coral reef butterflyfishes
Authors: Hodge Jennifer R. , Alim Chidera , Bertrand Nick G. , Lee Wesley , Price Samantha A. , Tran Binh , Wainwright Peter C. 
Published: May 2018

AbstractAntipredator defensive traits are thought to trade‐off evolutionarily with traits that facilitate predator avoidance. However, complexity and scale have precluded tests of this prediction in many groups, including fishes. Using a macroevolutionary approach, we test this prediction in butterflyfishes, an iconic group of coral reef inhabitants with diverse social behaviours, foraging strategies and antipredator adaptations. We find that several antipredator traits have evolved adaptively, dependent primarily on foraging strategy. We identify a previously unrecognised axis of diversity in butterflyfishes where species with robust morphological defences have riskier foraging strategies and lack sociality, while species with reduced morphological defences feed in familiar territories, have adaptations for quick escapes and benefit from the vigilance provided by sociality. Furthermore, we find evidence for the constrained evolution of fin spines among species that graze solely on corals, highlighting the importance of corals, as both prey and structural refuge, in shaping fish morphology.
Marine fisheries and future ocean conflict
Authors: Spijkers Jessica , Morrison Tiffany H , Blasiak Robert , Cumming Graeme S , Osborne Matthew , Watson James , Österblom Henrik 
Published: May 2018

AbstractConflict over marine fishery resources is a growing security concern. Experts expect that global changes in our climate, food systems and oceans may spark or exacerbate resource conflicts. An initial scan of 803 relevant papers and subsequent intensive review of 31 fisheries conflict studies, focused on subnational and international conflicts, suggests that four substantial scientific gaps need addressing to improve our understanding of the nature and drivers of fisheries conflict. First, fisheries conflict and levels of conflict intensity are not precisely defined. Second, complex adaptive systems thinking is underutilized but has the potential to produce more realistic causal models of fishery conflict. Third, comparative large‐scale data and suitably integrative methodologies are lacking, underscoring the need for a standardized and comparable database of fisheries conflict cases to aid extrapolation beyond single case‐studies. Fourth, there is room for a more widespread application of higher order concepts and associated terminology. Importantly, the four gaps highlight the homogenized nature of current methodological and theoretical approaches to understanding fishery conflict, which potentially presents us with an oversimplified understanding of these conflicts. A more nuanced understanding of the complex and dynamic nature of fishery conflict and its causes is not only scientifically critical, but increasingly relevant for policymakers and practitioners in this turbulent world.
Effects of acute intradialytic exercise on cardiovascular responses in hemodialysis patients
Authors: Jeong Jin Hee , Biruete Annabel , Fernhall Bo , Wilund Kenneth R. 
Published: May 2018

AbstractBackground: In patients with kidney failure requiring hemodialysis (HD) treatment, intradialytic exercise (IDEX) has been advocated for its feasibility and effectiveness in improving important health outcomes. However, IDEX as an adjunct therapeutic strategy is infrequently implemented, in part due to potential risks of IDEX, especially in patients with chronic volume overload. This study was performed to evaluate the safety of IDEX performed at different time points by examining its effect on intradialytic cardiovascular hemodynamics.Methods: In a randomized cross‐over study (n = 12), intradialytic changes in brachial, aortic, and cardiac hemodynamics and autonomic function were examined during a HD session; (1) without exercise; (2) with 30 min of IDEX performed in the first hour of treatment; or (3) with 30 min of IDEX in the third hour of treatment.Results: IDEX during either the first or third hour did not exacerbate hemodynamic instability during treatment regardless of patient's hydrations status. While there were transient increases in stroke volume, cardiac output, and heart rate during IDEX, intradialytic changes in brachial and aortic blood pressure, cardiac hemodynamics, and autonomic function were similar on days with and without IDEX.Conclusion: These results indicate that IDEX does not exacerbate hemodynamic instability during HD, regardless of a patient's hydration status or the timing of exercise.
Subclinical cardiovascular disease in patients starting contemporary protease inhibitors
Authors: González‐Cordón A , Doménech M , Camafort M , Martínez‐Rebollar M , Torres B , Laguno M , Rojas J , Loncà M , Blanco JL , Mallolas J , Gatell JM , de Lazzari E , Martínez E 
Published: May 2018

ObjectivesThe aim of the study was to assess changes in and factors associated with anatomical [carotid artery intima‐media thickness (CIMT)] and functional (arterial stiffness) markers of subclinical cardiovascular disease progression in antiretroviral‐naïve patients starting triple combination antiretroviral therapy containing contemporary protease inhibitors.MethodsThis was a planned substudy of the ATADAR (Metabolic Effects of Atazanavir/Ritonavir Versus Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine in naïve HIV‐1 Infected Patients) clinical trial (ClinicalTrials.gov identifier NCT01274780). ATADAR is a multicentre, randomized, open‐label clinical trial comparing the effects of ritonavir‐boosted atazanavir and darunavir, both with tenofovir/emtricitabine, in antiretroviral‐naïve HIV‐infected patients. Common CIMT and aortic augmentation index (AIx@75) were measured at baseline and after 12 months of follow‐up. Antiretroviral treatment, traditional cardiovascular risk factors and HIV‐related factors were assessed as potential predictors of CIMT and Aix@75 changes using linear regression analysis.ResultsThirty‐three patients were included in this pilot study. While CIMT significantly increased in the pooled population [median (interquartile range (IQR)) 68 (−13, 128) μm; P = 0.0511], AIx@75 did not [median (IQR) 1 (−6, 5)%; P = 0.8964]. Patients on darunavir showed a trend to faster CIMT progression than those on atazanavir [median change (IQR) 117 (−2, 143) vs. −6 (−58, 89) μm, respectively; P = 0.0917]. However, after adjustment in the multivariate analysis, a higher baseline Framingham score was the only factor associated with CIMT progression (coefficient 16.02; 95% confidence interval –1.04, 33.08; P = 0.064). AIx@75 change was not associated with any baseline factor.ConclusionsCIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral‐naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.
Cytokine expression in response to root repair agents
Authors: Oliveira R. R. , Tavares W. L. F. , Reis A. L. , Silva V. A. , Vieira L. Q. , Ribeiro Sobrinho A. P. 
Published: May 2018

AbstractAimTo evaluate the expression of TNF‐α, IL‐6, IFN‐γ, TGF‐β, IL‐4, IL‐10, RANKL, RANK and OPG on mouse calvarial bone treated with MTA, Geristore® and Emdogain®.MethodologyBone wounds were made on the heads of C57BL/6 mice, breaking the periosteum and the cortical surface of the calvaria. Each repair agent was inserted into sectioned Eppendorf microtubes and placed on the bone wound, and soft tissues were sutured. At 14 and 21 days, animals were sacrificed and the treated region was dissected. The calvaria bone was removed, and RNA was extracted. mRNA expression of the aforementioned cytokines was assessed using real‐time PCR. Data were analysed by nonparametric methods, including the Mann–Whitney and Kruskal–Wallis tests (P < 0.05).ResultsFollowing treatment with Emdogain® and MTA, mRNA expression of RANKL, RANK and OPG increased significantly (P < 0.05) between days 14 to 21. Geristore® did not alter the basal expression of these mediators during the same period of evaluation. Whilst treatment with Emdogain® did cause a significant increase in TNF‐α mRNA expression between days 14 and 21 (P < 0.05), treatment with MTA did not alter the basal expression of this cytokine at either experimental time point. However, TNF‐α mRNA expression was down‐regulated significantly at day 21 (P < 0.05) when Geristore® was applied. A significant increase in the mRNA expression of IL‐6, TGF‐β, IL‐10, IL‐4 and IFN‐γ was observed with Emdogain® and MTA treatment between days 14 to 21, whereas Geristore® reduced significantly the expression of IL‐6, TGF‐β and IL‐4 (P < 0.05).ConclusionThe clinical indication of these repair agents depends on the root resorption diagnosis. Whilst MTA and Emdogain® induce a pro‐ and anti‐inflammatory response early and late, respectively, Geristore® was not associated with an inflammatory reaction when compared with both repair agents.
Silver absorption and toxicity evaluation of silver wound dressings in 40 patients with chronic wounds
Authors: Brouillard C. , Bursztejn A.‐C. , Latarche C. , Cuny J.‐F. , Truchetet F. , Goullé J.‐P. , Schmutz J.‐L. 
Published: May 2018

AbstractBackgroundSilver‐containing dressings are considered to be safe even though there have been some reports of complications, including argyria and various organ system dysfunctions. Despite the widespread use of silver dressings, little research has been done regarding the absorption and toxicity of silver.ObjectiveWe aimed to study the systemic absorption of silver in patients with chronic inflammatory wounds and to determine associated factors of systemic silver absorption and evaluated its association with silver toxicity.Patients and methodProspective, longitudinal, observational, multicentre, open‐label pilot study. Patients from the Dermatology Departments of Lorraine (France) with the following inclusion criteria: (i) a chronic wound of more than 6 weeks and (ii) an ulcer needing silver‐containing dressing were included. Before and after 28 days of treatment, clinical characteristics of the wound were recorded; hemogram, hepatic and renal functions, albumin sera and serum silver level were measured.ResultsHalf of the cases displayed raised levels of silver after 1 month of treatment. Predictive factors for systemic silver absorption were wound area, anaemia and malnutrition with anaemia and malnutrition confirmed on multivariate analysis. Wound vascularization may also play a role, as a higher absorption was observed in cases of wound granulation without arterial components. No toxicity was detected. This work has also emphasized the slow elimination of silver from the body.ConclusionBoth long‐term application and iterative treatments with silver dressings should be discouraged, especially in the elderly, who often suffer from malnutrition and anaemia to avoid potential cumulative toxicity.
The effect of autoimmune blistering diseases on work productivity
Authors: Wang E.Q. , Radjenovic M. , Castrillón M.A. , Feng G.H.Y. , Murrell D.F. 
Published: May 2018

AbstractBackgroundAutoimmune blistering diseases (AIBD) are known to negatively impact upon quality of life (QoL); however, there is a paucity of research on the effect of AIBD on work productivity. AIBD can be quite disfiguring in terms of a patient's appearance due to their blistering nature.ObjectiveTo determine the impact of AIBD on work productivity and to determine whether patients are stigmatized at work due to their appearance.MethodsSixty‐one patients with AIBD completed the Work Productivity and Activity Impairment Questionnaire‐Specific Health Problem (WPAIQ‐SHP), the Dermatology Life Quality Index (DLQI), the Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment of Autoimmune Bullous Disease Quality of Life questionnaires (TABQOL).ResultsNon‐responders to treatment had more work and activity impairment compared to responders. Worse WPAIQ‐SHP scores were correlated with higher ABQOL, TABQOL and DLQI scores. Approximately 14.8% of subjects experienced stigmatization at work due to their appearance. The most common body areas stigmatized were easily visible sites, particularly the hands, arms and feet, with the majority of occurrences related to co‐workers; for some patients, this stigmatization occurred on a daily basis. Loss of productivity at work was statistically much higher in those with higher disease severity, ABQOL & TABQOL scores and in non‐responders to treatment.ConclusionAutoimmune blistering diseases negatively impacts upon work productivity and activity. Stigmatization was common in the workplace which leads to increased stress, itself a stimulator of pemphigus.
Outdoor environment, ozone, radionuclide‐associated aerosols and incidences of infantile eczema in Minsk, Belarus
Authors: Belugina I.N. , Yagovdik N.Z. , Belugina O.S. , Belugin S.N. 
Published: May 2018

AbstractBackgroundThe early occurrence of atopic dermatitis in infants may be influenced by urban air pollution.ObjectiveThe aim of this study was to determine the relationship between incidences of infantile eczema in children under 2 years of age and urban outdoor environmental factors.MethodsA 11‐year population‐based study was conducted in retrospective design. The age/gender‐adjusted incidence rates of infantile eczema were determined using the data of outpatient visits. We analysed 1965 cases with atopic dermatitis including infantile eczema in relation to the annual means of outdoor monitoring data from 2005 through 2015 in Minsk. Logistic regression and principal component analysis were performed to determine association between the annual means of air pollutants, meteorological variables and incidences of infantile eczema.ResultsHigher mean annual carbon monoxide, ammonia, formaldehyde, lead, particulate matter and ground‐level ozone were associated with high incidence rates of infantile eczema both in boys and girls. Higher nitrogen dioxide was associated with high incidence rates of infantile eczema in girls 1–2 years of age and boys 0–2 years of age. There were identified by principal component analysis five combinations of pollutants and meteorological factors. High incidence rates of infantile eczema were associated with the combinations contained higher levels of air pollutants and ultraviolet index, or lower β‐activity of the radionuclide‐associated aerosols. The higher phenol and formaldehyde levels the higher incidence rates of infantile eczema were observed among boys 0–1 years of age and girls 1–2 years of age. The higher total column ozone with lower lead level was associated with low incidence rates of infantile eczema among boys and girls 1–2 years of age.ConclusionUrban outdoor air pollutants and their combination with meteorological conditions may impact onset of infantile eczema in both genders.
Patient perceptions of clear/almost clear skin in moderate‐to‐severe plaque psoriasis: results of the Clear About Psoriasis worldwide survey
Authors: Armstrong A. , Jarvis S. , Boehncke W.‐H. , Rajagopalan M. , Fernández‐Peñas P. , Romiti R. , Bewley A. , Vaid B. , Huneault L. , Fox T. , Sodha M. , Warren R.B. 
Published: May 2018

AbstractBackgroundTherapeutic advances have made the achievement of clear/almost clear skin possible for many patients with moderate‐to‐severe plaque psoriasis.ObjectiveTo determine patient perceptions of the impact of psoriasis and of attaining clear/almost clear skin.MethodsGlobal survey of patients with moderate‐to‐severe psoriasis.ResultsA total of 8338 patients from 31 countries participated. The majority (57%) had not achieved self‐assessed clear/almost clear skin with their current therapy, and 56% of those who had not met this goal believed it would be impossible to do so. Among the patients who had clear/almost clear skin, 73% had not initiated their current treatment until >1 year after psoriasis diagnosis, and 28% had to wait >5 years. Eighty‐four percent of all respondents experienced discrimination and/or humiliation due to psoriasis, and many reported negative effects on work, intimate relationships, sleep and mental health. Patients without clear/almost clear skin reported that such achievement would open new possibilities, such as swimming (58%), a wider choice of clothing (40%), and meeting new people (26%). A limitation of this study, as with any survey‐based research, is that selection and recall bias may have been present. Additionally, respondent definitions of clear/almost clear skin were subjective and may have varied.ConclusionDespite the importance of clear/almost clear skin to psoriasis patients, most are still not achieving it, and many are unaware it is possible.