bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of land grabs on peasant households: The case of the floriculture sector in Oromia, Ethiopia
Authors: Abate Abebe Gizachew
Published: March 2019

This article investigates how appropriation of land for flower farm developments in Walmara district and Holeta town in Ethiopia’s Oromia region affected smallholders’ livelihoods. Between 1996 and 2018, the state expropriated 1487 hectares from Oromo farming communities for the flower industry with little or no compensation through the ‘eminent domain’ principle. This article demonstrates the effects of these actions on the rural poor in Oromia including threats to common property resources and farming plots, which constitute their basic livelihood units and intergenerational assets. By focusing on cases of land expropriation in the central highlands of Ethiopia, it challenges a common misconception that land grabs are occurring only on the periphery of the state. In this case, the entanglements of the export-oriented flower industry in global capitalism and the centralized state administration have led to destitution for most smallholders within 100 kilometres of the capital city. The study shows how policies associated with the Ethiopian developmental state accord priority to investors and state interests over local concerns, reinforcing wider concerns with dominant models of development.
The immunometabolic role of indoleamine 2,3-dioxygenase in atherosclerotic cardiovascular disease: immune homeostatic mechanisms in the artery wall
Authors: Ketelhuth Daniel F J
Published: March 2019

Coronary heart disease and stroke, the two most common cardiovascular diseases worldwide, are triggered by complications of atherosclerosis. Atherosclerotic plaques are initiated by a maladaptive immune response triggered by accumulation of lipids in the artery wall. Hence, disease is influenced by several non-modifiable and modifiable risk factors, including dyslipidaemia, hypertension, smoking, and diabetes. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the kynurenine pathway of tryptophan (Trp) degradation, is modulated by inflammation and regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. A large body of evidence indicates that IDO-mediated Trp metabolism is involved directly or indirectly in atherogenesis. This review summarizes evidence from basic and clinical research showing that IDO is a major regulatory enzyme involved in the maintenance of immunohomeostasis in the vascular wall, as well as current knowledge about promising targets for the development of new anti-atherosclerotic drugs.
Vitamin D Decreases Hepcidin and Inflammatory Markers in Newly Diagnosed Inflammatory Bowel Disease Paediatric Patients: A Prospective Study
Authors: Moran-Lev Hadar , Galai Tut , Yerushalmy-Feler Anat , Weisman Yosef , Anafy Adi , Deutsch Varda , Cipok Michal , Lubetzky Ronit , Cohen Shlomi
Published: March 2019

Background and Aims

The role of hepcidin in inflammatory bowel disease [IBD] in children with anaemia is poorly understood. However, it has been shown that vitamin D suppresses hepcidin expression. We aimed to assess serum hepcidin levels and the effect of vitamin D treatment on those levels in newly diagnosed IBD paediatric patients.

Methods

Eighty-five children were prospectively recruited in the Dana-Dwek Children’s Hospital [40 newly diagnosed IBD, 45 healthy controls, 47% female, mean age 13.5 ± 3.4 years]. Blood samples for measurement of interleukin 6 [IL-6], C-reactive protein [CRP], hepcidin, iron parameters and 25-hydroxyvitamin D [25-(OH)-D] levels were obtained at baseline. Patients with mild-to-moderate signs and symptoms of IBD were treated with 4000 units of vitamin D daily for 2 weeks, after which the blood tests were repeated.

Results

Basal hepcidin, IL-6, CRP and platelet counts were significantly higher, and haemoglobin, serum iron and transferrin levels were significantly lower in the IBD children compared to controls [p < 0.001]. Eighteen patients completed 2 weeks of treatment with vitamin D. Following treatment, serum 25-(OH)-D concentrations increased by 40% [from 22.5 to 32.5 ng/mL], and serum hepcidin, CRP and ferritin levels decreased by 81%, 81% and 40% [from 33.9 to 6.7 ng/mL, from 23.9 to 4.7 mg/L, and from 27 to 16 ng/mL, respectively] [p ≤ 0.001].

Conclusion

Serum hepcidin levels were significantly higher in IBD paediatric patients compared to controls. Following vitamin D treatment, serum hepcidin concentration decreased significantly. These findings suggest a potential role for vitamin D in treating anaemia in IBD children.

ClinicalTrials.gov number

NCT03145896
An analysis of general practitioners’ perspectives on patient safety incidents using critical incident technique interviews
Authors: Curran Ciara , Lydon Sinéad , Kelly Maureen E , Murphy Andrew W , O’Connor Paul
Published: March 2019

Background

General practitioners report difficulty in knowing how to improve patient safety.

Objectives

To analyse general practitioners’ perspectives of contributing factors to patient safety incidents by collecting accounts of incidents, identifying the contributory factors to these incidents, assessing the impact and likelihood of occurrence of these incidents and examining whether certain categories of contributory factors were associated with the occurrence of high-risk incidents.

Methods

Critical incident technique interviews were carried out with 30 general practitioners in Ireland about a patient safety incident they had experienced. The Yorkshire Contributory Factors Framework was used to classify the contributory factors to incidents. Seven subject matter experts rated the impact and likelihood of occurrence of each incident.

Results

A total of 26 interviews were analysed. Almost two-thirds of the patient safety incidents were rated as having a major-to-extreme impact on the patient, and over a third were judged as having at least a bimonthly likelihood of occurrence. The most commonly described active failures were ‘Medication Error’ (34.6%) and ‘Diagnostic Error’ (30.8%). ‘Situational Domain’ was identified as a contributory domain in all patient safety incidents. ‘Communication’ breakdown at both practice and other healthcare-provider interfaces (69.2%) was also a commonly cited contributory factor. There were no significant differences in the levels of risk associated with the contributory factors.

Conclusions

Critical incident technique interviews support the identification of contributory factors to patient safety incidents. There is a need to explore the use of the resulting data for quality and safety improvement in general practice.
A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus
Authors: Teo Su Hui Catherine , Wu Jian-Ping , Mok Chee-Keng , Tan Yee-Joo
Published: March 2019

The non-structural protein 1 (NS1) of influenza A virus (IAV) is a multifunctional protein that antagonizes host antiviral responses, modulating virus pathogenesis. As such, it serves as a good target for research and diagnostic assay development. In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. Indeed, mAb 19H9 exhibits broad cross-reactivity with IAV strains of different subtypes. The binding of mAb 19H9 to residue Y89 was further confirmed by the abrogation of interaction between NS1 and p85β. Additionally, mAb 19H9 also detected NS1 proteins expressed in IAV-infected cells, showing NS1 intracellular localization in the cytoplasm and nucleolus. To our knowledge, mAb 19H9 is the first murine mAb to bind at the juxtaposition between the N-terminal RNA-binding domain and C-terminal effector domain of NS1. It could serve as a useful research tool for studying the conformational plasticity and dynamic changes in NS1.
Role Dissonance in Foreign Policy: Russia, Power, and Intercountry Adoption
Authors: Breuning Marijke , Pechenina Anna
Published: March 2019

States often play multiple roles on the world stage, which need not fit together coherently. Moreover, foreign policy roles may be dissonant with one another: auxiliary roles may detract from the state's master role or status. What prompts decision makers to address role dissonance and role conflict?

Building on earlier role theory research, we develop a framework that theorizes when and how role dissonance turns into conflict between a state's master and auxiliary foreign policy roles. We theorize that role conflict may be addressed through modification rather than abandonment of an auxiliary role.

The theory is illustrated with a case study that traces Russia's attempt to reconcile dissonance between its major-power role and its auxiliary role as a sending country (in intercountry adoption). We show that the interplay between master and auxiliary roles is complex. States care about status but also address dissonant auxiliary roles and role conflict pragmatically.
Mapping health workforce development strategies across key global health agencies: an assessment of objectives and key interventions
Authors: Farrenkopf Brooke A , Lee Chung-Won
Published: March 2019

The political and financial commitment to addressing the global shortage of health workers is stronger than ever before. Therefore, the global effort to strengthen human resources for health (HRH) must be co-ordinated and aligned to strategically utilize the current momentum and create sustainable impact. This paper assesses HRH strategies to (1) create greater understanding on the collective global action towards improving HRH, and (2) identify opportunities for greater co-ordination to improve sustainable health workforce development. We searched published and grey literature to identify the HRH strategies of select large-scale global health organizations. The most common approaches were increasing the supply of health workers, facilitating training and education and improving health worker management capacities. Overall, our analysis shows there is a need to (1) improve co-ordination among development partners, (2) ensure strong engagement and leadership of national governments and (3) generate scientific evidence on the best approaches for sustainable workforce development.
Evolution of Sexual Dimorphism in Tube Blennies (Teleostei: Chaenopsidae)
Authors: Hastings Philip A
Published: March 2019

Synopsis

The study of sexual differences provides insights into selective factors operating on males and females, especially for clades exhibiting varied levels of dimorphism. Sexual differences in morphology and coloration (melanophores) were compiled for 66 of the 89 species of tube blennies (Blenniiformes, Chaenopsidae) from the systematic literature and examination of preserved specimens. Chaenopsids include essentially monomorphic species and those in which males and females differ in as many as 17 morphological and 14 coloration features. While the sexes of most species differ in coloration (at least at the time of breeding), they are morphologically similar in Acanthemblemaria, Hemiemblemaria, and Lucayablennius. While other genera exhibit an intermediate level of dimorphism, species of Coralliozetus, Cirriemblemaria, and Emblemaria are dramatically dimorphic. Character maps on a phylogenetic hypothesis indicate that this extreme level of dimorphism evolved independently in these genera. A complex history of evolution is implied by examination of jaw length with both increases and decreases in one or both sexes leading to either dimorphism or monomorphism. Several features related to shelter defense are monomorphic in species where both sexes inhabit shelters, but dimorphic where only males occupy shelters. Other dimorphic features increase the conspicuousness of male courtship and aggressive displays.
Ignorance, Debt, and Cryptocurrencies: The Old and the New in the Law and Economics of Concurrent Currencies*
Authors: Nabilou Hossein , Prüm André
Published: March 2019

Cryptocurrencies are expected to have a significant impact on banking, finance, and monetary systems. Due to the uncertainty as to the possible future trajectories of the evolving cryptocurrency ecosystem, governments have taken a relatively hands-off approach to regulating such currencies. This approach may be justified within the theoretical information-economics framework of this paper, which draws parallels between the information economics of money and quasi-money creation within the current central banking, commercial banking, and shadow banking systems with that of the cryptocurrency ecosystem. In particular, drawing lessons from the literature on the role of information in creating ‘safe assets’, in this paper the authors find that by building on symmetric (common) knowledge as to the inner workings of the Bitcoin Blockchain—though in a different way—bitcoin possesses a degree of endogenous information insensitivity typical of safe assets. This endogenous information insensitivity could support bitcoin’s promise of maturing into a viable store of value and a niche medium of exchange. This finding should not be overlooked in the policy discussions for potential future regulatory interventions in the cryptocurrency ecosystem.
Long-term outcome, relapse patterns, and toxicity after radiotherapy for orbital mucosa-associated lymphoid tissue lymphoma: implications for radiotherapy optimization
Authors: Lee Jeongshim , Yoon Jin Sook , Kim Jin-Seok , Koom Woong Sub , Cho Jaeho , Suh Chang-Ok
Published: March 2019

Objectives

Although mucosa-associated lymphoid tissue lymphoma (MALToma) is sensitive to radiation therapy (RT), the optimal RT dose and treatment volumes have not been established. This study aimed to assess the relapse patterns and outcomes of patients with orbital MALToma who underwent RT and to suggest implications for optimized RT.

Methods

We reviewed 212 patients (246 orbits) diagnosed with orbital MALToma who received RT between 1993 and 2013. Median RT dose was 25.2 Gy. Generally, conjunctival and eyelid lesions were irradiated with electrons, whereas retrobulbar and lacrimal gland lesions with photons. Lens shielding was used for 70% of treated eyes, mainly conjunctival and eyelid tumors.

Results

Relapse occurred in 29 patients. Among 11 patients with local relapse (LR), 4 were attributed to insufficient dose (n = 2) and improper RT volume (n = 2). The 10-year LR, contralateral orbit relapse, and distant relapse rates were 8.6%, 12.8% and 4.9%, respectively. Twelve patients died of disease-specific causes (n = 1) and intercurrent diseases (n = 11). The 10-year relapse-free survival, overall survival, and cause-specific survival rates were 69.7%, 88.2% and 98.8%, respectively. Grade 3 cataracts and nasolacrimal duct obstruction were observed in 27 and 4 orbits, respectively.

Conclusion

Low-dose RT with proper lens shielding is an appropriate treatment for orbital MALToma in terms of high disease control rate and acceptable morbidity. However, lower RT dose may be attempted to further reduce toxicity while maintaining excellent outcomes.
Effects of Laboratory Grade Limonene and a Commercial Limonene-Based Insecticide on Haematobia irritans irritans (Muscidae: Diptera): Deterrence, Mortality, and Reproduction
Authors: Showler Allan T , Harlien Jessica L , Perez de Léon Adalberto A
Published: March 2019

The horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae), is an important and cosmopolitan blood feeding ectoparasite of cattle. Resistance to conventional insecticides is increasingly problematic and alternative pesticides, including natural products, are being investigated. Limonene is a cyclic monoterpene repellent to some insects that occurs in citrus fruit rinds and in other plants. We assessed laboratory grade limonene and a commercial product, Orange Guard (5.8% AI limonene), against H. irritans irritans in terms of their contact effects upon contact on egg mortality, adults, and larval and pupal development; adult repellency as well as sublethal and fumigation effects. Egg viability declined when they were exposed to Orange Guard at concentrations of 1.45%, 2.9%, and 5.8% whereas laboratory grade limonene at 5.8% and 11.6% was ovicidal. Contact exposure of adult H. irritans irritans to 5.8% laboratory grade limonene and 2.9% Orange Guard caused up to 100 and 88% knockdown (immobilization), respectively. At higher concentrations, laboratory grade limonene and Orange Guard resulted in less, and often shorter periods of knockdown. Although direct contact of 2.9 and 5.8% laboratory grade limonene caused mortality it was negligible when flies were sprayed directly with undiluted Orange Guard. Female H. irritans irritans exposed to sublethal concentrations of Orange Guard did not reduce the numbers of eggs produced, but the undiluted product reduced egg hatchability. Interestingly, limonene and Orange Guard attracted adult H. irritans irritans at concentrations <0.1%. We suggest that the attractancy of unformulated pure limonene might be useful for trapping H. irritans irritans adults.
The Syrian Refugee Crisis and Foreign Policy Decision-Making in Jordan, Lebanon, and Turkey
Authors: Tsourapas Gerasimos
Published: March 2019

How does forced migration affect the politics of host states and, in particular, how does it impact states’ foreign policy decision-making? The relevant literature on refugee politics has yet to fully explore how forced migration affects host states’ behavior. One possibility is that they will employ their position in order to extract revenue from other state or nonstate actors for maintaining refugee groups within their borders. This article explores the workings of these refugee rentier states, namely states seeking to leverage their position as host states of displaced communities for material gain. It focuses on the Syrian refugee crisis, examining the foreign policy responses of three major host states—Jordan, Lebanon, and Turkey. While all three engaged in post-2011 refugee rent-seeking behavior, Jordan and Lebanon deployed a back-scratching strategy based on bargains, while Turkey deployed a blackmailing strategy based on threats. Drawing upon primary sources in English and Arabic, the article inductively examines the choice of strategy and argues that it depended on the size of the host state's refugee community and domestic elites’ perception of their geostrategic importance vis-à-vis the target. The article concludes with a discussion of these findings’ significance for understanding the international dimension of the Syrian refugee crisis and argues that they also pave the way for future research on the effects of forced displacement on host states’ political development.
Outsourcing Microbiology Services in Medical Centers: Is It Worth It?
Authors: Penton Manuel E , Otto Caitlin , Hammerschlag Margaret R
Published: March 2019

Background

Outsourcing of microbiology laboratory services is a growing trend in US medical centers. Data on the actual impact of outsourcing on patient care, safety, and medical education, including costs, are limited. The objective of this study was to examine the published literature on the potential benefits and harms when medical centers outsource common microbiology services.

Methods

We conducted a 16-step literature search of PubMed and Embase. Articles were selected for full-text review if their content matched our key questions: (1) What are the potential benefits of outsourcing core microbiology laboratory testing? (2) What are the potential harms to patient care and medical education when medical centers outsource essential microbiology services?

Results

The initial search yielded 6111 unique published articles; 36 were selected for full-text review, which resulted in the identification of 8 articles that addressed our key questions (2 editorials, 3 editorials with observational data, 1 survey, 1 case series, and 1 study of blood culture transport). These articles described a variety of issues, including longer turnaround times for blood cultures that resulted in delays in diagnosis and treatment, errors that resulted in patient morbidity, limited cost savings, and communication barriers.

Conclusions

In this study, with the exception of the blood culture transport study, we found no published prospective studies that quantified the effects of outsourcing microbiology services on patient care, patient safety, or medical education. However, these largely anecdotal reports suggest that outsourcing microbiology services may have a detrimental impact on medical education, especially infectious disease training programs.
Public Understanding of Cigarette Smoke Chemicals: Longitudinal Study of US Adults and Adolescents
Authors: Jeong Michelle , Noar Seth M , Zhang Dongyu , Mendel Jennifer R , Agans Robert P , Boynton Marcella H , Byron M Justin , Baig Sabeeh A , Ranney Leah M , Ribisl Kurt M , Brewer Noel T
Published: March 2019

Introduction

The US Food and Drug Administration has increased communication efforts that aim to raise public awareness of the harmful constituents (ie, chemicals) in cigarette smoke. We sought to investigate whether the public’s awareness of these chemicals has increased in light of such efforts.

Methods

Participants were national probability samples of 11 322 US adults and adolescents recruited in 2014–2015 (wave 1) and 2016–2017 (wave 2). Cross-sectional telephone surveys assessed awareness of 24 cigarette smoke chemicals at both timepoints.

Results

The proportion of US adults aware of cigarette smoke chemicals did not differ between waves 1 and 2 (25% and 26%, p = .19). In contrast, awareness of chemicals among adolescents fell from 28% to 22% (p < .001), mostly due to lower awareness of carbon monoxide, arsenic, benzene, and four other chemicals. Belief that most of the harmful chemicals in cigarette smoke come from burning the cigarette also fell from waves 1 to 2 (adults: 31% vs. 26%; adolescents: 47% vs. 41%, both ps < .05). Participants were more likely to be aware of cigarette smoke chemicals if they had been exposed to anti-smoking campaign advertisements (p < .05) or had previously sought chemical information (p < .05). Cigarette smoke chemical awareness did not differ between smokers and nonsmokers.

Conclusion

Awareness of cigarette smoke chemicals remains low and unchanged among adults and decreased somewhat among adolescents. The association of chemical awareness with information exposure via campaigns and information seeking behavior is promising. More concerted communication efforts may be needed to increase public awareness of cigarette smoke chemicals, which could potentially discourage smoking.

Implications

Awareness of the toxic chemicals in cigarette smoke may contribute to quitting. The US Food and Drug Administration is making efforts to increase public awareness of these chemicals. Two national surveys (2014–2017) found that chemical awareness was low among adults and adolescents. Although awareness did not change among adults, awareness among adolescents dropped over time. In addition, exposure to anti-smoking campaigns and chemical information seeking behavior were associated with higher awareness of chemicals in cigarette smoke. Campaigns and other efforts may be needed to increase awareness of cigarette smoke chemicals.
2018 Langley Award for Basic Research on Nicotine and Tobacco: Bringing Precision Medicine to Smoking Cessation
Authors: Bierut Laura J
Published: March 2019

Introduction

Large segments of the world population use combustible cigarettes, and our society pays a high price for smoking, through increased healthcare expenditures, morbidity and mortality. The development of combustible cigarette smoking requires the initiation of smoking and a subsequent chain of behavioral transitions from experimental use, to established regular use, to the conversion to addiction. Each transition is influenced by both environmental and genetic factors, and our increasing knowledge about genetic contributions to smoking behaviors opens new potential interventions.

Methods

This review describes the journey from genetic discovery to the potential implementation of genetic knowledge for the treatment of tobacco use disorder.

Results and Conclusions

The field of genetics applied to smoking behaviors has rapidly progressed with the identification of highly validated genetic variants that are associated with different smoking behaviors. The large scale implementation of this genetic knowledge to accelerate smoking cessation represents an important clinical challenge in precision medicine.
Beachcombers: Vagrancy, Empire, and Robert Louis Stevenson’s The Ebb-Tide
Authors: Robinson Alistair
Published: March 2019

Runaways, castaways and renegades, the beachcombers lived in the Pacific Islands, and were the vagrants of the South Seas. Historically, they were most prominent in the early nineteenth century, and belonged to the medial phase between the Pacific Islanders’ first contact with Europeans, and the formal colonization that followed. Roaming from one island to another, trading skills and goods with their inhabitants, the beachcombers were driven further and further afield as Western powers began to annex the Pacific Islands. By the 1880s and 1890s they had been thoroughly displaced by the missionaries and merchants who settled there; however, in spite of this, or rather because of it, the beachcomber became an increasingly prominent figure in British culture during this period. This article examines the importance of the beachcomber in the imperial imagination. It explores how the beachcomber was ambiguously presented as both an imperial pathfinder and a degraded buccaneer in popular novels and the periodical press, and how these portrayals were key to the public’s understanding of the Pacific Islands. This cultural and historical discussion then provides the context for a close reading of Robert Louis Stevenson’s The Ebb-Tide (1894). Here the beachcomber, a vagrant figure who captivated Stevenson’s imagination, is shown to be essential to his construction and critique of empire in the Pacific.
A Theory of Multiperiod Debt Structure
Authors: Huang Chong , Oehmke Martin , Zhong Hongda
Published: March 2019

We develop a theory of multiperiod debt structure. A simple trade-off between the termination threat required to make debt repayments incentive compatible and the desire to avoid early liquidation determines the number of repayments, their timing, and amounts. As firms increase their borrowing, they add periodic risky repayments from the back of the maturity structure, with the time between repayments increasing in cash-flow risk. Cash-flow growth or a significant risk-free cash-flow component limits the number of risky repayments. Firms with a significant risk-free cash-flow component choose dispersed maturity profiles with smaller, relatively safe repayments every period, rather than riskier periodic repayments.

Received May 31, 2017; editorial decision October 8, 2018 by Editor Stijn Van Nieuwerburgh.
Autoantibodies to Mi-2 alpha and Mi-2 beta in patients with idiopathic inflammatory myopathy
Authors: Richards Michaelin , García-De La Torre Ignacio , González-Bello Yelitza C. , Vázquez-Del Mercado Mónica , Andrade-Ortega Lilia , Medrano-Ramírez Gabriel , Navarro-Zarza Jose Eduardo , Maradiaga-Ceceña Marco , Loyo Esthela , Rojo-Mejía Armando , Gómez Graciela , Seaman Andrea , Fritzler Marvin J. , Koenig Martial , Mahler Michael
Published: March 2019

Objectives

The objective of this study was to compare the results obtained from different assays for the detection of anti-Mi-2 antibodies, which are important markers in the diagnosis of DM.

Methods

The study included 82 patients (68 females/14 males), most of whom had DM (n = 57), followed by PM (n = 16) and juvenile DM (n = 9). All samples were tested using a novel particle-based multi-analyte technology (PMAT) (Inova Diagnostics, research use only) in parallel with a line immunoassay (LIA: Euroimmun). To assess clinical specificity for the PMAT assay, a total of 775 disease and healthy controls were tested.

Results

29 samples were positive by at least one test for anti-Mi-2 antibodies. Of those, 24 were Mi-2β LIA+, five were Mi-2α LIA+ and 23 Mi-2 PMAT+. The comparison shows varying agreement between the different methods (kappa 0.27–0.77). When LIA results were used as reference for receiver operating characteristics analysis, high area under the curve values were found for both PMAT vs LIA Mi-2α and LIA Mi-2β. When analysing the results in the context of the myositis phenotype, PMAT associated closest with the DM phenotype. In the control group, 3/775 controls (all low levels) were anti-Mi-2+ resulting in a sensitivity and specificity of 28.1% and 99.6%, respectively.

Conclusion

Overall, good agreement was found between LIA and PMAT for anti-Mi-2 antibodies, which is important for the standardization of autoantibodies. Anti-Mi-2β antibodies measured by PMAT tend be more highly associated with the clinical phenotype of DM.
Oligohydramnios: should it be considered a risk factor for developmental dysplasia of the hip?
Authors: Manoukian Dimitrios , Rehm Andreas
Published: March 2019

Breech, family history, first born and female sex are the main risk factors described for developmental dysplasia of the hip (DDH). Foot abnormalities and oligohydramnios have also been listed. Recent studies have discredited torticollis, multiple gestation pregnancy, mode of delivery and prematurity as risk factors. Definition of oligohydramnios in the literature is inconsistent. Our aim was to investigate the term oligohydramnios and evaluate whether it should be considered a risk factor for DDH. All live births in our institution between 2001 and 2014 were included. We identified all pregnancies classed as reduced amniotic fluid (AF) or oligohydramnios over that period. Data on DDH, breech presentation, female sex and positive family history were collected. The significance level was set to 5%. We identified 73 990 live births, 3408 pregnancies were classed as reduced AF or oligohydramnios. The incidence of DDH (Graf type IIb and higher) was 1: 1000 (75 babies, 18 bilateral). Oligohydramnios/reduced AF was found in 12 (16%) DDH babies. Breech presentation was found in 24 (32%), positive family history in 19 (25%) and female sex in 71 (94.7%). Oligohydramnios was found to be associated with a higher odds ratio (OR) for DDH [OR = 3.9, 95% confidence interval (CI): 2.1–7.3] as were breech presentation (OR = 10.6, 95% CI: 6.5–17.1) and female sex (OR = 19.1, 95% CI: 7–52.4). All examined risk factors showed statistical significance (P < 0.05). A regression analysis was performed to control for interactions and confounding factors and confirmed the findings. On the basis of our findings the diagnosis of reduced AF/oligohydramnios in consecutive antenatal sonographic scans should be regarded as an independent risk factor for DDH and be considered in any future studies regarding DDH. Level of evidence: Level IV: Case series.
The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review With Meta-Analysis of Randomized Controlled Trials*
Authors: Putzu Alessandro , Daems Anne-Marie , Lopez-Delgado Juan Carlos , Giordano Vito Federico , Landoni Giovanni
Published: March 2019

Objectives:

The effects of vitamin C administration on clinical outcome in critically ill patients remain controversial.

Data Sources:

Online databases were searched up to October 1, 2018.

Study Selection:

We included randomized controlled trials on the use of vitamin C (any regimen) in adult critically ill patients versus placebo or no therapy.

Data Extraction:

Risk ratio for dichotomous outcome and standardized mean difference for continuous outcome with 95% CI were calculated using random-effects model meta-analysis.

Data Synthesis:

Forty-four randomized studies, 16 performed in ICU setting (2,857 patients) and 28 in cardiac surgery (3,598 patients), published between 1995 and 2018, were included in the analysis. In ICU patients, vitamin C administration was not associated with a difference in mortality (risk ratio, 0.90; 95% CI, 0.74–1.10; p = 0.31), acute kidney injury, ICU or hospital length of stay compared with control. In cardiac surgery, vitamin C was associated to a reduction in postoperative atrial fibrillation (risk ratio, 0.64; 95% CI, 0.52–0.78; p < 0.0001), ICU stay (standardized mean difference, –0.28 d; 95% CI, –0.43 to –0.13 d; p = 0.0003), and hospital stay (standardized mean difference, –0.30 d; 95% CI, –0.49 to –0.10 d; p = 0.002). Furthermore, no differences in postoperative mortality, acute kidney injury, stroke, and ventricular arrhythmia were found.

Conclusions:

In a mixed population of ICU patients, vitamin C administration is associated with no significant effect on survival, length of ICU or hospital stay. In cardiac surgery, beneficial effects on postoperative atrial fibrillation, ICU or hospital length of stay remain unclear. However, the quality and quantity of evidence is still insufficient to draw firm conclusions, not supporting neither discouraging the systematic administration of vitamin C in these populations. Vitamin C remains an attractive intervention for future investigations aimed to improve clinical outcome.
Primary Cutaneous Acral CD8+ T-Cell Lymphoma—A Single Center Review of 3 Cases and Recent Literature Review
Authors: Tjahjono Leonardo A. , Davis Mark D. P. , Witzig Thomas E. , Comfere Nneka I.
Published: March 2019

The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49–62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2–5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity.
AL-Amyloidoma of the Skin—A Rare Manifestation of Primary Cutaneous Marginal Zone Lymphoma
Authors: Ueberdiek Stefan , Kempf Werner , Kretschmer Lutz , Peter Schön Michael , Mitteldorf Christina
Published: March 2019

AL-amyloidoma is considered to be a variant of primary cutaneous marginal zone lymphoma (pcMZL). A 51-year-old white man presented a 2 × 2-cm erythematous to brownish waxy plaque on the back of the scalp. The plaque was first noticed 16 years ago. It was asymptomatic, and the patient was otherwise healthy. The lesion was excised. Histological examination revealed dermal deposits of amyloid and a subtle perivascular infiltrate, predominately consisting of plasma cells. Infiltrating cells expressed CD79a, bcl2, and IgG and were negative for bcl6, CD56, and IgM. A monoclonal light-chain expression of lambda (lambda:kappa = 10:1) was demonstrated by in situ hybridization. The diagnosis of pcMZL, presenting as an AL-amyloidoma, was made because staging procedures excluded systemic manifestation of lymphoma, monoclonal gammopathy, and systemic amyloidosis. Cutaneous amyloid deposits with monoclonal plasma cell proliferation can occur as a result of monoclonal gammopathy/plasmocytoma or as a rare manifestation of pcMZL. Systemic B-cell lymphoma and systemic monoclonal plasma cell proliferations have to be excluded.
Cutaneous Crospovidone: A Newly Described Foreign Body Due to Illicit Drug Abuse
Authors: Hoyt Brian S. , Aaron Denise M. , Yan Shaofeng , Linos Konstantinos D.
Published: March 2019

Crospovidone, a polymer of poly N-vinyl-2-pyrrolidone, is an inert insoluble disintegrant found in pharmaceutical tablets. This material has been encountered in the lungs of intravenous drug users and embolized with other components such as talc and microcrystalline cellulose. More recently, crospovidone has also been described in the gastrointestinal tract. We present 2 cases of cutaneous crospovidone deposition resulting from subcutaneous injection of crushed tablets, commonly known as “skin popping.” Clinical presentation includes painful, inflamed papules, nodules, or ulcers with overlying eschar. Crospovidone has a distinct and reproducible histochemical staining profile. Histologic recognition of this material is important because it can guide clinicians in their diagnosis and management decisions.
Amyloid-Associated Alopecia: A Reappraisal Including Its Pathophysiology
Authors: Magro Cynthia M. , Solomon Garron J. , Kendrick Mary Jo J. , Momtahen Shabnam
Published: March 2019

Primary systemic amyloidosis has a varied clinical presentation, making it one of the great masqueraders of other disease entities in clinical medicine. The association of amyloidosis with alopecia is uncommon with at least 22 cases reported in the literature mostly in the setting of systemic amyloidosis. Alopecia in these patients occurs either as the initial presentation of the systemic amyloidosis or it happens during the disease course. The occurrence of amyloid alopecia associated with light chain (LC) restricted plasmacytic infiltrates in the absence of systemic amyloidosis, however, it is not well known. We report 3 cases of LC-associated amyloidosis presenting with alopecia, whereby there was evidence of a systemic plasma cell dyscrasia in 2 of the patients, one of whom developed multiple myeloma. None of the patients had systemic amyloidosis. Skin presentation in the patient with multiple myeloma was characterized by a diffuse form of alopecia affecting the entire scalp, eyebrow, and axillary and pubic hair in contrast to the localized form of alopecia noted in the other 2 patients. The mechanism by which LC-associated amyloidosis eventuates in this pattern of nonscarring alopecia potentially reflects the affinity of this form of amyloid for dermatan sulfate. Dermatan sulfate is found at highest concentrations within the adventitial dermis of the superficial to mid isthmic portions of the anagen hair follicles likely interfering with the hair cycle and induces early hair follicle involution. The result is a pattern of alopecia that can clinically and to some extent pathologically resemble either androgenetic alopecia or alopecia areata.
Necrotizing Granulomas in a Patient With Psoriasis and Sarcoidosis After Adalimumab—Medication-Induced Reaction or Reactivation of Latent Disease?
Authors: Turkowski Yana , Konnikov Nellie , Mahalingam Meera
Published: March 2019

In this report, we describe a case of a patient with a clinical history of systemic sarcoidosis and psoriasis who developed biopsy-confirmed perforating and necrotizing cutaneous granulomas after 12 months of treatment with adalimumab, a tumor necrosis factor-alpha–inhibiting, anti-inflammatory, biologic medication, prescribed for the patient's psoriasis. Although rare reports of a “sarcoidosis-like” reaction associated with select tumor necrosis factor-alpha agents exist, to the best of our knowledge, perforating and necrotizing cutaneous granulomas after treatment with adalimumab has not been previously reported. Given the patient's history of systemic sarcoidosis, the differential diagnosis includes reactivation of latent sarcoidosis with adalimumab as a trigger.
Phenylephrine Attenuated Sepsis-Induced Cardiac Inflammation and Mitochondrial Injury Through an Effect on the PI3K/Akt Signaling Pathway
Authors: Li Hong-mei , Li Kai-ying , Xing Yun , Tang Xiang-xu , Yang Duo-meng , Dai Xiao-meng , Lu Da-xiang , Wang Hua-dong
Published: March 2019

Objective:

To investigate whether phenylephrine (PE) inhibits sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.

Methods:

A rat model of sepsis was established by cecal ligation and puncture. PE and/or wortmannin (a PI3K inhibitor) were administered to investigate the role of PI3K/Akt signaling in mediating the effects of PE on inhibiting sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury. Hematoxylin–eosin staining, echocardiography, and Langendorff system were used to examine the myocardial injury and function. The concentrations of TNF-α and IL-6 were analyzed by enzyme-linked immunosorbent assay. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, mitochondria-related fusion/fission proteins, and PI3K/Akt signaling pathway–associated proteins were analyzed by Western blotting.

Results:

PE improved the cardiac function and survival in septic rats. PE decreased TNF-α, IL-6, ICAM-1, VCAM-1, and myeloperoxidase contents in the myocardium of septic rats. Meanwhile, PE increased the fusion-related proteins and decreased the fission-related proteins in the myocardial mitochondria of septic rats. On the other hand, PE activated the PI3K/Akt signaling pathway in the cecal ligation and puncture–treated rats, and all the protective effects of PE were abolished by wortmannin.

Conclusions:

PE attenuated sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.
Comparison of Efficacy and Safety of Bleb Needle Revision With and Without 5-Fluorouracil for Failing Trabeculectomy Bleb
Authors: Kim Jin-Soo , Kim Hae Jin , Na Kyeong Ik , Kim Young Kook , Park Ki Ho , Jeoung Jin Wook
Published: March 2019

Précis:

Bleb needle revision with and without 5-FU showed similar success rates over the course of a long-term follow-up. A greater total number of needle revisions was identified as a risk factor for procedural failure.

Purpose:

The purpose of the study was to investigate the efficacy and safety of bleb needle revision with adjunctive 5-fluorouracil (5-FU) subconjunctival injection in large-scaled patients with failing trabeculectomy bleb.

Materials and Methods:

A retrospective chart review was performed on a total of 113 eyes of 106 subjects who had undergone trabeculectomy followed by needle revision and been followed up for at least 6 months. The subjects were divided into 2 groups according to whether they had also undergone concurrent adjunctive 5-FU subconjunctival injection. Two definitions of failure were derived irrespective of IOP-lowering medication use and were assessed at each follow-up visit: (1) IOP>21 mm Hg or >85% of preoperative IOP or reoperation for glaucoma, (2) IOP>18 mm Hg or >80% of preoperative IOP or reoperation for glaucoma.

Results:

A total of 78 eyes of 73 subjects underwent the simple needle revision procedure and 35 eyes of 33 subjects underwent needle revision with subconjunctival 5-FU injection. There was no significant adverse event for either group and no significant IOP difference in any of the observational periods between them (P=0.867). There was also no statistically significant difference in the total number of IOP-lowering medications between the groups (P=0.199). The success rate at 24 months after the first needle revision was 45.6% (95% CI: 33.7, 56.7) in simple revision group and 44.6% (95% CI: 27.7, 60.2) in 5-FU needle revision group by failure 1, 36.3% (95% CI: 25.4, 47.2) and 32.9% (95% CI: 18.0, 48.6) by failure 2, respectively. A greater total number of needle revisions was the significant risk factors for needle revision failure (HR=2.25 and P=0.001 according to failure 2).

Conclusions:

Bleb needle revision with 5-FU subconjunctival injection is a safe procedure for failing trabeculectomy bleb. Bleb needle revision with and without 5-FU were equally likely to succeed.
Altered gray matter volume in sensorimotor and thalamic regions associated with pain in localized provoked vulvodynia: a voxel-based morphometry study
Authors: Bhatt Ravi R. , Gupta Arpana , Rapkin Andrea , Kilpatrick Lisa A. , Hamadani Kareem , Pazmany Els , Van Oudenhove Lukas , Stains Jean , Aerts Leen , Enzlin Paul , Tillisch Kirsten , Mayer Emeran A. , Labus Jennifer S.
Published: March 2019

Multimodal neuroimaging studies provide support for a role of alterations in sensory processing circuits and endogenous pain modulatory systems in provoked vestibulodynia (PVD). In this study, we tested the hypotheses that PVD compared with healthy controls (HCs) would demonstrate gray matter volume (GMV) alterations in regions associated with sensorimotor, corticothalamic, and basal ganglia circuits. We also tested the replicability of previously reported gray matter increases in basal ganglia and hippocampal volumes in PVD vs HCs. In addition, disease specificity of GMV alterations were examined by comparing PVD with another chronic pain disorder. Finally, we examine whether GMV alterations are correlated with symptom measures. Structural magnetic resonance imaging was obtained in 119 premenopausal women (45 PVD, 45 HCs, and 29 irritable bowel syndrome [IBS]). A voxel-based morphometry analysis was applied to determine group differences in the hypothesized regions of interest. Compared with HCs, PVD women exhibited greater GMV in the basal ganglia, hippocampus, and sensorimotor cortices. Compared to patients with IBS, women with PVD had greater GMV in the hippocampus, and sensorimotor network, but lower GMV in the thalamus and precentral gyrus. Regional GMV alterations were associated with patient reports of pain during intercourse and muscle tenderness. The current findings provide further evidence that GMV is increased in PVD compared with HCs in several regions of the sensorimotor network and the hippocampus in patients with PVD. In addition, GMV distinct alterations in the sensorimotor network were identified between 2 pelvic pain disorders, PVD compared with IBS.
A deeper look at pain variability and its relationship with the placebo response: results from a randomized, double-blind, placebo-controlled clinical trial of naproxen in osteoarthritis of the knee
Authors: Treister Roi , Honigman Liat , Lawal Oluwadolapo D. , Lanier Ryan K. , Katz Nathaniel P.
Published: March 2019

Previous studies have shown a robust correlation between variability of clinical pain scores and responsiveness to placebo (but not active drug) in pain studies, but explanations for these relationships are lacking. We investigated this further by assessing relationship between the Focused Analgesia Selection Test (FAST), a psychophysical method that quantifies pain reporting variability in response to experimental stimuli, variability of daily clinical pain scores as captured using diary, and response to treatment in the context of a randomized controlled crossover trial of naproxen vs placebo in knee osteoarthritis. Evoked pain using the Staircase-Evoked Pain Procedure served as the primary efficacy endpoint. Variability of daily pain scores and the FAST were assessed at baseline. Fifty-five subjects completed the study and were included in the analyses. Our results indicated a statistically significant, moderate linear relationship between variability of clinical and experimental pain reports (r = −0.416, P = 0.004). Both correlated with the placebo response (r = 0.393, P = 0.004; r =−0.371, P = 0.009; respectively), but only the FAST predicted the treatment difference between naproxen and placebo, as demonstrated both in a regression model (P = 0.002, Beta = 0.456, t = 3.342) and in a receiver operating characteristic curve (0.721) analysis. Our results extend previous findings to include a correlation between experimental pain variability and the placebo response and suggest that experimental pain variability is a better predictor of patients who respond preferentially to drug over placebo. A theoretical model unifying these observations is proposed, and practical implications are discussed.