bluuebunny/crossref_metadata_2025 huggingface dataset:
HTRA1, an age‐related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1
Authors: Lin Michael K. , Yang Jin , Hsu Chun Wei , Gore Anuradha , Bassuk Alexander G. , Brown Lewis M. , Colligan Ryan , Sengillo Jesse D. , Mahajan Vinit B. , Tsang Stephen H.
Published: May 2018

High‐temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age‐related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key. We assess the high‐risk genotype at 10q26 by proteomic comparison of protein levels of RPE cells with and without the mutation. We show HTRA1 protein level is increased in high‐risk RPE cells along with several extracellular matrix proteins, including known HTRA1 cleavage targets LTBP‐1 and clusterin. In addition, two novel targets of HTRA1 have been identified: EFEMP1, an extracellular matrix protein mutated in Doyne honeycomb retinal dystrophy, a genetic eye disease similar to AMD, and thrombospondin 1 (TSP1), an inhibitor of angiogenesis. Our data support the role of RPE extracellular deposition with potential effects in compromised barrier to neovascularization in exudative AMD.
Imaging resilience and recovery in alcohol dependence
Authors: Charlet Katrin , Rosenthal Annika , Lohoff Falk W. , Heinz Andreas , Beck Anne
Published: May 2018

Background and aims

Resilience and recovery are of increasing importance in the field of alcohol dependence (AD). This paper describes how imaging studies in man can be used to assess the neurobiological correlates of resilience and, if longitudinal, of disease trajectories, progression rates and markers for recovery to inform treatment and prevention options.

Methods

Original papers on recovery and resilience in alcohol addiction and its neurobiological correlates were identified from PubMed and have been analyzed and condensed within a systematic literature review.

Results

Findings deriving from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies have identified links between increased resilience and less task‐elicited neural activation within the basal ganglia, and benefits of heightened neural pre‐frontal cortex (PFC) engagement regarding resilience in a broader sense; namely, resilience against relapse in early abstinence of AD. Furthermore, findings consistently propose at least partial recovery of brain glucose metabolism and executive and general cognitive functioning, as well as structural plasticity effects throughout the brain of alcohol‐dependent patients during the course of short‐, medium‐ and long‐term abstinence, even when patients only lowered their alcohol consumption to a moderate level. Additionally, specific factors were found that appear to influence these observed brain recovery processes in AD, e.g. genotype‐dependent neuronal (re)growth, gender‐specific neural recovery effects, critical interfering effects of psychiatric comorbidities, additional smoking or marijuana influences or adolescent alcohol abuse.

Conclusions

Neuroimaging research has uncovered neurobiological markers that appear to be linked to resilience and improved recovery capacities that are furthermore influenced by various factors such as gender or genetics. Consequently, future system‐oriented approaches may help to establish a broad neuroscience‐based research framework for alcohol dependence.
What is the effect of physical activity on duration and mode of delivery? Secondary analysis from the Norwegian Fit for Delivery trial
Authors: Sanda Birgitte , Vistad Ingvild , Sagedal Linda R. , Haakstad Lene A.H. , Lohne‐Seiler Hilde , Torstveit Monica K.
Published: May 2018

Introduction

The beneficial effects of physical activity during pregnancy for the mother and offspring have been reported by several studies but there are conflicting results concerning the possible effect of physical activity on the course of labor and risk of cesarean delivery. This study presents secondary analyses from the Norwegian Fit for Delivery randomized controlled trial, aiming at studying the effect of a lifestyle intervention including group exercise classes, as well as the possible influence of physical activity level in late pregnancy, on labor outcomes.

Material and methods

Healthy nulliparous women with singleton pregnancy were randomized to an intervention group, n = 303 (dietary counseling and twice‐weekly exercise classes) or a control group, n = 303 (standard care). The participants were analyzed both by randomization and as a cohort comparing women with lowest (quartile 1, 0 metabolic equivalent of task‐hours moderate‐to‐vigorous physical activity/week) (n = 140) vs. highest (quartile 4, ≥16 metabolic equivalent of task‐hours moderate‐to‐vigorous physical activity/week) (n = 131) physical activity level in late pregnancy, assessed with the International Physical Activity Questionnaire.

Result

The intervention group had a longer first stage of labor compared with the control group (293 ± 202 min vs. 257 ± 181 min, p = 0.030). No differences between the randomization groups were seen for time spent in second stage of labor, prolonged labor or mode of delivery. In the total sample, women with the highest physical activity level had lower odds ratio (OR) of acute cesarean delivery (OR 0.33, 95% CI 0.11–0.97, p = 0.044) than did those with the lowest physical activity‐level.

Conclusion

A significantly longer first stage of labor was observed in the intervention group than in the control group. A high physical activity level in late pregnancy was associated with lower odds of acute cesarean delivery compared with a low physical activity level.
Hospital readmissions, mortality and potentially inappropriate prescribing: a retrospective study of older adults discharged from hospital
Authors: Counter David , Millar James W. T. , McLay James S.
Published: May 2018

Aims

Applying version 2 of the STOPP/START criteria to discharge prescriptions of older adults discharged from a general medical unit, the aim of this study is to assess potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) and their association with hospital readmission and mortality.

Methods

Discharge medications, co‐morbidities and patient demographics were recorded over an 8‐month period for consecutive emergency admissions of patients aged ≥65 years. PIMs and PPOs were identified using version 2 of the STOPP/START criteria. Multivariate analysis for association of PIMs and PPOs with re‐admissions and mortality during the follow‐up period were assessed using binary logistic regression.

Results

Data for 259 patients with a mean age of 77 (65–99, 51% female) were analysed. At discharge, the mean number of co‐morbidities and medications per patient were 5.4 (SD: 2.1 range: 0–14) and 9.3 (SD: 4.0 range: 1–31) respectively. During the follow‐up period (mean 41.5 months, SD: 2.0 range: 38–46 months), 50.2% of patients had died and the median number of readmissions was two (IQR: 1–4 range: 0–33). Prescription of more than five medications was significantly associated with PIMs and PPOs (OR: 2.75, 95% CI: 1.34–5.62 and OR 3.20, 95% CI: 1.57–6.54 respectively). Presence of a PIM was associated with three or more readmissions (OR: 2.43 95% CI: 1.19–4.98) and PPOs with mortality (OR: 1.88, 95% CI: 1.09–3.27).

Conclusions

Using version 2 of the STOPP/START criteria, the presence of PIMs and/or PPOs in older adults discharged from hospital is significantly associated with repeated hospital admissions and mortality respectively.
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

Aims

The 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.

Methods

Neonates 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.

Results

Thirty‐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.

Conclusion

Based 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

Objectives

To evaluate the impact of serum vitamin D level on male lower urinary tract symptoms (LUTS).

Patients and Methods

Men 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.

Results

Vitamin 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.

Conclusions

Vitamin 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

Background

We 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.

Objective

To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics.

Methods

FeNO, 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).

Results

Asthmatics 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 Relevance

Sensitization 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

Antipredator 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

Conflict 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

Background: 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

Objectives

The 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.

Methods

This 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.

Results

Thirty‐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.

Conclusions

CIMT 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

Aim

To 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®.

Methodology

Bone 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).

Results

Following 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).

Conclusion

The 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.
Smartphone, video games and other new technologies on hand joints in patients with psoriasis
Authors: Kluger N.
Published: May 2018

Linked article: This article is commentary on by M. Megna et al., pp. e457–e458 in this issue. To view this article visit https://doi.org/10.1111/jdv.15056
Beta‐blockers for treatment of autoimmune blistering dermatosis
Authors: Abdelmaksoud A. , Vestita M.
Published: May 2018

Linked article: This article is commented on by D. Miyamoto et al., pp. e459–e461 in this issue. To view this article visit https://doi.org/10.1111/jdv.15057
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

Background

Silver‐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.

Objective

We 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 method

Prospective, 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.

Results

Half 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.

Conclusion

Both 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.
Smartphone and video games overuse effects on hand joints: time for screening interventions?
Authors: Megna M. , Gisonni P. , Balato N.
Published: May 2018

Linked article: This article is commented on by N. Kluger, p. e457 in this issue. To view this article visit https://doi.org/10.1111/jdv.15053
Beta‐adrenoceptor expression in pemphigus foliaceus
Authors: Miyamoto D. , Dias A.B.T. , Aoki V. , Burnier M.N.
Published: May 2018

Linked article: This article is commentary on by A. Abdelmaksoud et al., pp. e458–e459 in this issue. To view this article visit https://doi.org/10.1111/jdv.15054
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

Background

Autoimmune 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.

Objective

To determine the impact of AIBD on work productivity and to determine whether patients are stigmatized at work due to their appearance.

Methods

Sixty‐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).

Results

Non‐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.

Conclusion

Autoimmune 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

Background

The early occurrence of atopic dermatitis in infants may be influenced by urban air pollution.

Objective

The 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.

Methods

A 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.

Results

Higher 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.

Conclusion

Urban 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

Background

Therapeutic advances have made the achievement of clear/almost clear skin possible for many patients with moderate‐to‐severe plaque psoriasis.

Objective

To determine patient perceptions of the impact of psoriasis and of attaining clear/almost clear skin.

Methods

Global survey of patients with moderate‐to‐severe psoriasis.

Results

A 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.

Conclusion

Despite the importance of clear/almost clear skin to psoriasis patients, most are still not achieving it, and many are unaware it is possible.
Accurate determination of energy requirements in hospitalised patients with parenteral nutrition
Authors: Quiroz‐Olguín G. , Medina‐Vera I. , Serralde‐Zúñiga A. E. , Gulias‐Herrero A. , Sánchez‐Rosales A. I. , Guevara‐Cruz M.
Published: May 2018

Background

The prescription of parenteral nutrition (PN) in hospitalised patients requires an estimation of the energy requirements. Most studies employing prediction equations (PEs) to estimate energy requirements have focused on critically ill patients. The present study aimed to evaluate several PEs of the resting energy expenditure (REE) to identify the most accurate equation for estimating the REE required for PN.

Methods

This cross‐sectional and descriptive study included patients hospitalised with medical or surgical diagnoses, making them candidates for PN. Epidemiological data, the reason for hospital admission, nutritional screening results, characteristics of the PN administered and REE by indirect calorimetry (IC) were recorded and, subsequently, PEs were calculated.

Results

In total, 116 patients were recruited with a mean (SD) age of 56.7 (13.8) years and body mass index of 21.3 (4.25) kg m−2. The diagnosis was medical in 52% of patients and surgical in 48%. The mean (SD) REEs of patients, according to IC, were: 6.11 (1.18) MJ [1461 (281) kcal]; and according to PEs: Mifflin, 5.07 (1.05) MJ [1212 (252) kcal]; Owen, 5.43 (0.72) MJ [1298 (172) kcal]; Harris–Benedict, 5.38 (0.85) MJ [1285 (204) kcal]; Ireton‐Jones, 6.20 (1.69) MJ [1481 (403) kcal]; and short equation, 6.12 (0.92) MJ [1464 (220) kcal]. A comparison of the results obtained for the REE by IC and with PEs indicated that the short equation had less bias than the other equations, with an accuracy of 54%

Conclusions

In hospitalised patients who receive PN, determination of the REE should ideally be made by IC. PEs are acceptable but not exact and so their estimation could overfeed or underfeed the patient.
FYCO1 mediates clearance of α‐synuclein aggregates through a Rab7‐dependent mechanism
Authors: Saridaki Theodora , Nippold Markus , Dinter Elisabeth , Roos Andreas , Diederichs Leonie , Fensky Luisa , Schulz Jörg B. , Falkenburger Björn H.
Published: May 2018

Parkinson's disease can be caused by mutations in the α‐synuclein gene and is characterized by aggregates of α‐synuclein protein. We have previously shown that over‐expression of the small GTPase Rab7 can induce clearance of α‐synuclein aggregates. In this study, we investigate which Rab7 effectors mediate this effect. To model Parkinson's disease, we expressed the pathogenic A53T mutant of α‐synuclein in HEK293T cells and Drosophila melanogaster. We tested the Rab7 effectors FYVE and coiled‐coil domain‐containing protein 1 (FYCO1) and Rab‐interacting lysosomal protein (RILP). FYCO1‐EGFP‐decorated vesicles containing α‐synuclein. RILP‐EGFP also decorated vesicular structures, but they did not contain α‐synuclein. FYCO1 over‐expression reduced the number of cells with α‐synuclein aggregates, defined as visible particles of EGFP‐tagged α‐synuclein, whereas RILP did not. FYCO1 but not RILP reduced the amount of α‐synuclein protein as assayed by western blot, increased the disappearance of α‐synuclein aggregates in time‐lapse microscopy and decreased α‐synuclein‐induced toxicity assayed by the Trypan blue assay. siRNA‐mediated knockdown of FYCO1 but not RILP reduced Rab7‐induced aggregate clearance. Collectively, these findings indicate that FYCO1 and not RILP mediates Rab7‐induced aggregate clearance. The effect of FYCO1 on aggregate clearance was blocked by dominant negative Rab7 indicating that FYCO1 requires active Rab7 to function. Electron microscopic analysis and insertion of lysosomal membranes into the plasma membrane indicate that FYCO1 could lead to secretion of α‐synuclein aggregates. Extracellular α‐synuclein as assayed by ELISA was, however, not increased with FYCO1. Coexpression of FYCO1 in the fly model decreased α‐synuclein aggregates as shown by the filter trap assay and rescued the locomotor deficit resulting from neuronal A53T‐α‐synuclein expression. This latter finding confirms that a pathway involving Rab7 and FYCO1 stimulates degradation of α‐synuclein and could be beneficial in patients with Parkinson's disease.

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MrpC, a CRP/Fnr homolog, functions as a negative autoregulator during the Myxococcus xanthus multicellular developmental program
Authors: McLaughlin Maeve , Bhardwaj Vidhi , Feeley Brooke E. , Higgs Penelope I.
Published: May 2018

MrpC, a member of the CRP/Fnr superfamily of transcriptional regulators, plays a key role in coordination of the multicellular developmental program in Myxococcus xanthus. Previous reports suggest MrpC is subject to complex regulation including activation by an unusual LonD‐dependent proteolytic processing event that removes its unique N‐terminal peptide, producing the isoform MrpC2. MrpC2 is proposed to positively autoregulate and regulate transcription of hundreds of genes necessary for both the aggregation and sporulation phases of the developmental program. We demonstrate here that mrpC expression bifurcates corresponding to different cell populations within the developmental program. During our analysis of regulatory events controlling this process, we demonstrate that MrpC2 is not an active isoform; rather, the N‐terminal peptide is instead essential for MrpC function in vivo. We also demonstrate that MrpC is instead a negative autoregulator and represses its own expression by specifically competing with its enhancer binding protein, MrpB. These results provide an additional rare example of CRP/EBP coordinated regulation, and significantly revise the model for control of the central developmental transcriptional activator of the M. xanthus developmental program.
Individualized immunoglobulin treatment in pediatric patients with primary humoral immunodeficiency disease
Authors: Patel Niraj C.
Published: May 2018

Primary immunodeficiency diseases (PIDD) are a group of genetic conditions that are generally considered to be under‐diagnosed, and gaps may exist in the knowledge of treatment options. This review focuses on the diagnosis of pediatric patients with primary antibody deficiency and considerations for treatment with immunoglobulin (IgG) to optimize multiple dosing variables and minimize adverse events. The possibility of individualizing IgG therapy in clinical practice represents, in this field, the next pivotal step with the goal of improving the quality of life of pediatric patients with PIDD.
An IL‐10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis
Authors: Roy S. , Mukhopadhyay D. , Mukherjee S. , Moulik S. , Chatterji S. , Brahme N. , Pramanik N. , Goswami R. P. , Saha B. , Chatterjee M.
Published: May 2018

Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL‐4/IL‐13 and IL‐10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL‐4‐driven monocytes/macrophages [M(IL‐4)] were studied namely intramonocytic CD206+, circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel‐like factor 4 (KLF4), peroxisome proliferator‐activated receptors (PPAR)‐γ and arginase‐I (ARG‐I) in peripheral blood mononuclear cells was unaltered. However, markers for IL‐10‐driven monocytes/macrophages [M(IL‐10)], namely soluble CD163, intramonocytic IL‐10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL‐10), along with the absence of markers for M(IL‐4). Taken together, in human VL, manipulation of these IL‐10 polarized monocytes‐macrophages may pave the way for improved therapeutic outcomes.
Gene‐edited plants on the plate: the ‘CRISPR cabbage story’
Authors: Jansson Stefan
Published: May 2018

The European Union (EU) has very strict regulations for genetically modified plants, but gene editing challenges the basis of the legislation. Genome editied plants with no foreign DNA added were according to the Swedish competent authority Jordbruksverket falling outside of the EU definition of genetically modified plants, and should hence not be regulated. This article describes the background to this interpretation and also how plants gene edited using CRISPR‐Cas9 (a Brassica deletion mutant) for the first (?) time were grown in a garden, cooked and eaten, and the subsequent media attention. Furthermore, it also adresses the troubles authorities in other European countries have to handle these plants.
Environmental Issues in the South China Sea: Legal Obligation and Cooperation Drivers
Authors: Chu Hoi Nguyen , Dang Vu Hai
Published: May 2018

Recently, we have been witnessing a critical level of a the degradation of the marine environment and depletion of fish stocks in the South China Sea. This has many adverse consequences on the politics, economics of the countries in the region as well as on the socio-economic life of the coastal population. One of the activities that has been causing serious damage to the marine environment and living resources of the South China Sea is the large-scale land reclamation and artificial island construction undertaken by China in the Spratly and Paracel islands recently. These activities have caused severe harm to the precious coral reef environment and thus, violated the obligation to preserve and protect fragile ecosystems and the habitat of depleted, threatened or endangered species under the international law of the seaThe paper explores the impact of China’s large-scale land reclamation and artificial island construction activities on the marine biodiversity of the South China Sea, explains what the legal obligation under the international law of States to protect and preserve the marine environment is and suggests a number of options in order to bring a halt to such activities and restore the damaged marine ecosystem. The paper puts particular emphasis on the cooperation drivers torwards a healthy, prosperous and peaceful South China Sea, which also contribute to the management and possibly, resolution of the current disputes in this region.Keywords: marine environmental issues, legal obligation, cooperation drivers, large-scale reclamation, artificial islands, blue solutions and fragile ecosystems.
Reductions in national cardiometabolic mortality achievable by food price changes according to Supplemental Nutrition Assistance Program (SNAP) eligibility and participation
Authors: Wilde Parke Edward , Conrad Zach , Rehm Colin D , Pomeranz Jennifer L , Penalvo Jose L , Cudhea Frederick , Pearson-Stuttard Jonathan , O’Flaherty Martin , Micha Renata , Mozaffarian Dariush
Published: May 2018

Background

Suboptimal diets are a major contributor to cardiometabolic disease (CMD) mortality, and substantial disparities exist for both dietary quality and mortality risk across income groups in the USA. Research is needed to quantify how food pricing policies to subsidise healthy foods and tax unhealthy foods could affect the US CMD mortality, overall and by Supplemental Nutrition Assistance Program (SNAP) eligibility and participation.

Methods

Comparative risk analysis based on national data on diet (National Health and Nutrition Examination Survey, 2003–2012) and mortality (mortality-linked National Health Interview Survey) and meta-analyses of policy-diet and diet-disease relationships.

Results

A national 10% price reduction on fruits, vegetables, nuts and whole grains was estimated to prevent 19 600 CMD deaths/year, including 2.6% (95% UI 2.4% to 2.8%) of all CMD deaths among SNAP participants, 2.7% (95% UI 2.4% to 3.0%) among SNAP-eligible non-participants and 2.6% (95% UI 2.4% to 2.8%) among SNAP-ineligible non-participants. Adding a national 10% tax on sugar-sweetened beverages (SSBs) and processed meats would prevent a total of 33 700 CMD deaths/year, including 5.9% (95% UI 5.4% to 7.4%) of all CMD deaths among SNAP participants, 4.8% (95% UI 4.4% to 5.2%) among SNAP-eligible non-participants and 4.1% (95% UI 3.8% to 4.5%) among SNAP-ineligible non-participants. Adding a SNAP-targeted 30% subsidy for the same healthy foods would offer the largest reductions in both CMD mortality and disparities.

Conclusion

National subsidies for healthy foods and taxes on SSBs and processed meats would each reduce CMD mortality; taxes would also reduce CMD mortality more steeply for SNAP participants than for non-participants.
Natural experiment examining the longitudinal association between change in residential segregation and youth cardiovascular health across race/ethnicity and gender in the USA
Authors: D’Agostino Emily M , Patel Hersila H , Ahmed Zafar , Hansen Eric , Mathew M Sunil , Nardi Maria I , Messiah Sarah E
Published: May 2018

Background

Identifying how racial/ethnic residential segregation and mobility may impact health can guide innovative strategies for reducing youth disparities.

Methods

This natural experiment examined the association between change in residential segregation and cardiovascular health outcomes across race/ethnicity and gender for youth (n=2250, mean age 9.1 years, 54% male; 51% Hispanic, 49% non-Hispanic black (NHB); 49% high area poverty) attending a multisite park-based afterschool fitness programme in Florida, USA. Two-level generalised linear mixed models with random intercepts for park effects were fit to test the change in segregation–cardiovascular health association over two school years.

Results

After covariate adjustment (individual-level gender, race/ethnicity, age, time and park-area poverty), greater improvements in cardiovascular health including body mass index percentile, sum of skinfold thicknesses, systolic/diastolic blood pressure percentiles and 400 m run time were found for youth who attended the program in a less segregated area compared with their home area (p<0.05 for all outcomes). NHB girls showed the greatest cardiovascular health improvements. Specifically, compared with the reference group (no change in segregation), skinfold thicknesses and systolic blood pressure percentiles decreased 17% (incidence rate ratio (IRR) 95% CI 0.81 to 0.86) and 16% (IRR 95% CI 0.82 to 0.87), respectively, versus 1% increase for both outcomes (IRR 95% CI 0.98 to 1.05) and (IRR 95% CI 0.98 to 1.05), respectively, for movement to less versus more segregated areas.

Conclusion

In light of a continually expanding youth obesity epidemic, the global effort to reduce health inequities may be supported through Parks and Recreation Departments given potential to expand geographic mobility for low resource subgroups.