bluuebunny/crossref_metadata_2025 huggingface dataset:
Trade and Investment Agreements and the Global Politics of Health
Authors: Holden Chris , Hawkins Benjamin
Published: January 2018

This chapter examines the politics of trade and investment agreements and how they interact with the politics of health at the global and domestic levels. The chapter first examines the operation of the World Trade Organization (WTO) and its implications for health, illustrating this with a WTO dispute between Indonesia and the United States involving the latter’s ban on flavoured cigarettes. It then examines aspects of the ‘next generation’ of trade and investment agreements that have particular implications for health policy, notably investor-state dispute settlement and regulatory cooperation. The analytical focus of this chapter is on political processes and political actors at the global and domestic levels that interact to produce trade policy and its impacts on health.
Congress and National Security
Authors: Serafino Nina M. , Ekmektsioglou Eleni G.
Published: January 2018

Congress may not be seen as a major player in U.S. national security, but it is congressional action that sets the foundation on which national security policy is constructed. Congressional legislation empowers the actions of federal departments and agencies, authorizes and appropriates funds, and defines the roles and missions of different offices (and who can occupy them). Yet Congress’s role in national security can vary based on the president’s ability to respond quickly to set the national security agenda; the president’s acumen, political skills, and popularity; and structural and political limitations on how the legislature can impose its preferences on the executive branch. Congress finds it harder to prevail when the president responds in a crisis using preexisting powers and authorities, but it can constrain the executive branch using constitutional prerogatives along with informal means such as influencing public opinion.
Alliances, Military Basing, and Logistics
Authors: Vielledent Marc C.
Published: January 2018

The United States has long enjoyed an essentially unopposed ability to project power and sustain its security forces dispersed throughout the world. However, the uncertainty facing the global security environment, including tenuous alliances, fiscal constraints, and a decline in overseas basing, has increased tensions in emerging areas of potential conflict. These factors are driving change regarding the United States’ defense posture and access agreements abroad. While the preponderance of overseas capability outweighs the preponderance of U.S. forces, deterrence continues to underpin the overarching national security strategy. However, deterrence options impacted by the lack of resilience and investment in distributed logistics and sustainment are generating an additional range of variables and conditions for operators on the ground to consider in shared and contested domains.
Intellectual Property, Development, and Access to Knowledge
Authors: Deere Birkbeck Carolyn
Published: January 2018

This chapter examines debates on intellectual property (IP) and development in the wider context of issues relating to IP and the public interest. It also considers how calls for greater attention to development in the global IP system relate to campaigns for “access to knowledge” (A2K). After reviewing the longstanding debates on IP and public policy issues as well as the substance of debates on IP, development, and A2K, the article discusses the engagement of developing countries in the international IP system up until the end of the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) negotiations. It proceeds with a review of post-TRIPS debates on the Agreement itself, before concluding with an analysis of the continuing challenges of addressing public interest and development concerns in the increasingly complex global IP system.
Running an Effective DBT Consultation Team
Authors: Sayrs Jennifer H. R.
Published: January 2018

DBT team is one of the essential modes of comprehensive DBT and focuses on improving and maintaining the motivation and capability of DBT providers. This chapter provides an overview of DBT team, including descriptions of core differences between a traditional team and a DBT team (e.g., therapy for the therapist, dialectics). It describes team agreements and structure, including the team agenda and elements of effective team meetings. It reviews DBT team roles (e.g., team leader, meeting leader) and how they may improve team functioning; this chapter also describes how to manage team difficulties using DBT principles and strategies, and provides several examples. While the ideas presented here have worked for many teams, they should not be considered rules; creating the structure and solutions unique to one’s own team, based on DBTs principles, will maximize the chances of a healthy, effectively run DBT team.
Deceptive Advertising and Taking Responsibility for Others
Authors: Shiffrin Seana Valentine
Published: January 2018

This chapter considers how the U.S. law of deceptive advertising embeds within it an extended form of responsibility, making advertisers sometimes responsible for consumers’ mistakes. The chapter justifies this pattern of liability as a division of moral labor that bolsters consumers’ ability to trust the quality of the food supply and the representations made about it. It answers worries about paternalism, arguing that the law is not predicated on distrust of consumers, but facilitates consumer autonomy, permitting consumers to direct their scarce time and energy to projects of their own choosing. The chapter also answers freedom of speech concerns about restricting advertisers’ ability to make factually true representations. It emphasizes that commercial speakers have a special responsibility to ensure accurate uptake by consumers because property law affords commercial producers the ability to exclude consumers and their representatives from verifying speech about speakers’ products for themselves.
Eat Y’Self Fitter
Authors: van Dyke Christina
Published: January 2018

Attitudes toward healthy eating and dietary choices are increasingly important components of how people conceive of (and judge) both themselves and others. This chapter examines orthorexia—a condition in which the subject becomes obsessed with identifying and maintaining the ideal diet, rigidly avoiding foods perceived as unhealthy or harmful—and it argues that the condition represents an extreme manifestation of sociocultural norms that people are all being pushed toward. These norms are highly gendered, however, and women and men are thus sometimes portrayed as if they were striving toward radically different goals in the elusive quest for perfect health. Yet what makes orthorexia destructive to both men and women is ultimately a common urge to transcend rather than to embrace the realities of embodiment. In short, orthorexia is best understood as a manifestation of age-old anxieties about human finitude and mortality—anxieties that current dominant sociocultural forces prime people to experience and express in unhealthy attitudes toward healthy eating.
Paternalism, Food, and Personal Freedom
Authors: Conly Sarah
Published: January 2018

This chapter explores the supposed difference between health regulations that are generally accepted (e.g., inspections for salmonella) and ones that are found excessively paternalistic (portion size controls), and it argues that the two are basically the same: in each case government tries to protect people from choices that do not advance their ends. Coercion is not bad when it keeps people from making choices that would promote obesity and heart disease, since most people value health more than they value the availability of large portions of junk food. Paternalists recognize that people also value things other than health, such as social outings involving food and celebrations of culture that feature traditional meals. The chapter argues that eating habits have always evolved, however, and an evolution that reflects healthier options in particular is no more destructive of shared social gatherings or cultural traditions than any other change.
Food Labor Ethics
Authors: Doggett Tyler , Holmes Seth
Published: January 2018

This chapter is an overview of some of the ethical issues regarding food workers. Paying special attention to farm workers and the conditions under which they work, it discusses, among other things, the infliction of pain and suffering on workers and their treatment as tools, children, or animals. It discusses also the coercion and exploitation of workers as well as the sexism, racism, and classism they face. In addition, this chapter discusses how these conditions arise at the societal level and what can be done about them.
Greek and Roman Terminologies of Slavery
Authors: Zelnick-Abramovitz Rachel
Published: January 2018

The Greeks had no single generic term for ‘slave’, but a variety of terms for diverse relations of dependence and unfree people, many of which were also used to describe free people. Although much less complex, the Roman slave terms show similar features. Despite the ambiguity of the ancient terminology, we may make inferences about various aspects of unfreedom, about ambiguities in social and juridical distinctions, and about attitudes to menial work. This chapter examines Greek and Roman terminologies, aiming at detecting their semantic fields and pointing to a possible identical semantic process behind the adoption of the main slave terms in Greece, Rome, and the modern western world.
Orthopaedic Management of Leg-length Discrepancy in Proteus Syndrome: A Case Series
Authors: Crenshaw Molly M. , Goerlich Cara G. , Ivey Lauren E. , Sapp Julie C. , Keppler-Noreuil Kim M. , Scott Allison C. , Biesecker Leslie G. , Tosi Laura L.
Published: January 2018

Introduction:

Proteus syndrome (PS) is a rare mosaic disorder comprising asymmetric bony and soft tissue overgrowth leading to significant morbidity. Placement of growth inhibition hardware with subsequent epiphyseal arrest improves leg-length and angular deformities in pediatric patients without PS. The purpose of this study was to review the surgical approach and present outcomes, complications, and recommendations in 8 patients with PS and leg-length discrepancy (LLD).

Methods:

We conducted a retrospective chart review of 8 patients with PS whose primary reason for surgery was LLD. Patients were eligible if they met clinical diagnostic criteria for PS and if the National Institutes of Health team performed at least 1 of their surgical interventions between 2005 and 2015. Surgical techniques included growth inhibition, with tension band plates, applied ≥1 times, and epiphyseal arrest.

Results:

Eight patients, followed for an average of 4.6 years (range, 1.0 to 7.1 y) after the index procedure, were included in this analysis. Average age at first LLD surgery was 9.4 years (range, 6.1 to 13.6 y); the average LLD was 3.4 cm (range, 0.4 to 7.0 cm) at presentation, and 5.0 cm (range, 1.8 to 10.0 cm) at the time of the first LLD surgery. Participants underwent 23 total surgeries (range, 1 to 5 per patient) and 7 patients have completed surgical intervention. For the 7 patients who did not require overcorrection the average LLD at the last clinical encounter was 2.6 cm (range, 0.6 to 7.2 cm). We encountered 2 complications: 2 patients developed mild knee valgus, which responded to standard guided growth techniques.

Conclusions:

This case series suggests that growth inhibition and epiphyseal arrest in children with PS can reduce LLD with few complications. Careful monitoring, rapid mobilization, deep venous thrombosis prophylaxis, and sequential compression devices were also integral elements of our surgical protocol.

Level of Evidence:

Level IV.
ALK Gene Fusions in Epithelioid Fibrous Histiocytoma: A Study of 14 Cases, With New Histopathological Findings
Authors: Kazakov Dmitry V. , Kyrpychova Liubov , Martinek Petr , Grossmann Petr , Steiner Petr , Vanecek Tomas , Pavlovsky Michal , Bencik Vladimir , Michal Michael , Michal Michal
Published: January 2018

Previous studies showed that ALK is often positive in epithelioid fibrous histiocytoma (EFH). Two cases of EFH with ALK gene fusions have been recorded. Our objective was to study a series of EFH to present histopathological variations of EFH, identify novel ALK gene fusions, and determine whether there is a correlation between histopathological features and particular gene. We investigated 14 cases of EFH, all ALK immunopositive. The cases were assessed histopathologically as well as for ALK and TFE-3 rearrangements using FISH and ALK gene fusions using next-generation sequencing. The analysis of the sequencing results was performed using the Archer Analysis software (v5; ArcherDX Inc). The study group consisted of 8 female and 6 male patients, ranging in age from 18 to 79 years (mean 42 years; median 37.5 years). All presented with a solitary lesion. Microscopically, most lesions were polypoid and composed of epithelioid cells with ample cytoplasm. In addition, a variable number of bi-, tri-, or multinucleated, spindled, multilobated, cells with eccentric nuclei, cells with nuclear pseudoinclusions, mucinous, and grooved cells were admixed. In 5 cases, the predominant epithelioid cell component consisted of rather small cells, whereas spindled cells dominated in 3 cases. Of these, 2 lesions were composed rather of pale eosinophilic to clear cells, occasioning a resemblance to PEComa or leiomyoma. Immunohistochemically, all cases expressed ALK and 11 were positive for TFE-3. The break apart test for ALK was positive in 11 cases, whereas specimens from the remaining 3 cases were not analyzable. ALK genes fusions were found in all but 3 cases and included SQSTM1-ALK (3), VCL-ALK (3), TMP3-ALK (2), PRKAR2A-ALK (1), MLPH-ALK (1), and EML4-ALK (1). No correlation between histological features and type of ALK fusion was found. TFE-3 break apart test was negative. It is concluded that ALK-immunopositive EFH shows ALK gene fusions that involve various protein-coding genes, implicated in a variety of biological processes. Rare variants of EFH rather consist of spindled “non-epithelioid” cells.
Macular and Multifocal PERG and FD-OCT in Preperimetric and Hemifield Loss Glaucoma
Authors: Kreuz André C. , de Moraes Carlos G. , Hatanaka Marcelo , Oyamada Maria K. , Monteiro Mario L.R.
Published: January 2018

Purpose:

To evaluate the ability of macular and multifocal (mf) pattern electroretinogram (PERG) to differentiate preperimetric glaucoma (PG) and glaucoma with hemifield loss (GHL) from controls, to compare the discrimination ability of PERG and fourier-domain optical coherence tomography (FD-OCT), and to assess the relationship between measurements.

Patients and Methods:

Standard automated perimetry, steady-state and transient PERG and mfPERG measurements were obtained from PG (n=14, 24 eyes), GHL (n=5, 7 eyes), and controls (n=19, 22 eyes). Circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula, and segmented macular layer thicknesses on FD-OCT were investigated. Measurements were compared using mixed effects linear models. The relationships between measurements and the diagnostic performance of each technology were assessed.

Results:

Compared with controls, average P50 peak time transient PERG responses were reduced in PG and GHL, whereas average latency and amplitude steady-state and mfPERG responses were abnormal only in GHL. cpRNFL and macular thickness measurements in PG and GHL differed significantly from controls. A significant relationship was found between PERG and most FD-OCT or SAP parameters. Partial least squares discriminant analysis revealed that OCT parameters, along with mfPERG and transient PERG parameters had similar ability to discriminate PG and GHL from healthy controls.

Conclusions:

PERG and OCT parameters may be abnormal, with significant correlations between measurements, in PG eyes. Both technologies may be useful for detection of early glaucoma.
Relationship of Macular Thickness and Function to Optical Microangiography Measurements in Glaucoma
Authors: Rao Harsha L. , Riyazuddin Mohammed , Dasari Srilakshmi , Puttaiah Narendra K. , Pradhan Zia S. , Weinreb Robert N. , Mansouri Kaweh , Webers Carroll A.B.
Published: January 2018

Purpose:

The purpose of this article was to evaluate the relationship between macular optical microangiography (OMAG), ganglion cell-inner plexiform layer (GCIPL) thickness, and visual sensitivity measurements of different macular sectors in primary open-angle glaucoma.

Methods:

In a cross-sectional study, 39 eyes of 26 primary open-angle glaucoma patients underwent optical coherence tomography imaging and 10-2 visual field examination of the macula in the same session. Linear regression models were used to evaluate the relationships between OMAG, GCIPL thickness, and visual sensitivity measurements in different macular sectors. Strength of relationship was reported as coefficient of determination (R
2).

Results:

R
2 values for the associations between OMAG and GCIPL thickness measurements ranged from 0.37 in the temporal sector to 0.56 in the inferior macular sector. R
2 values for the association between OMAG and visual sensitivity measurements ranged from 0.23 in the superior to 0.53 in the inferior macular sector. R
2 values for the association between GCIPL thickness and visual sensitivity measurements ranged from 0.15 in the superior to 0.62 in the temporal sector.

Conclusions:

The strongest associations between OMAG, GCIPL thickness, and visual sensitivity measurements were found in the inferior macular sector. The association of OMAG with GCIPL thickness measurements was as strong as the association between OMAG and visual sensitivity measurements in the inferior macular sector.
Smad4 Loss Correlates With Higher Rates of Local and Distant Failure in Pancreatic Adenocarcinoma Patients Receiving Adjuvant Chemoradiation
Authors: Herman Joseph M. , Jabbour Salma K. , Lin Steven H. , Deek Matthew P. , Hsu Charles C. , Fishman Elliot K. , Kim Sinae , Cameron John L. , Chekmareva Marina , Laheru Daniel A. , Narang Amol K. , Pawlik Timothy M. , Hruban Ralph H. , Wolfgang Christopher L. , Iacobuzio-Donahue Christine A.
Published: January 2018

Objectives

The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined whether Smad4 tumor status was associated with outcomes after adjuvant chemoradiation (CRT) for resected PDAs.

Methods

Patients treated with adjuvant CRT were identified (N = 145). Smad4 status was determined by immunolabeling and graded as intact or lost. Kaplan-Meier method and multivariable competing risk analyses were performed.

Results

On multivariate competing risk analysis, Smad4 loss was associated with increased risk of local recurrence (LR) (hazard ratio, 2.37; 95% confidence interval, 1.10–5.11; P = 0.027), distant failure (DF) (hazard ratio, 1.71; 95% confidence interval, 1.03–2.83; P = 0.037), and synchronous LR and DF at first recurrence (14.9 % vs 5.3%, P = 0.07) compared with Smad4 intact cancers. Smad4 loss was not associated with median overall survival (22 vs 22 months; P = 0.63) or disease-free survival (lost [13.6 months] vs intact [13.5 months], P = 0.79).

Conclusions

After PDA resection and adjuvant CRT, Smad4 loss correlated with higher risk of LR and DF, but not with survival. Smad4 loss may help predict which surgical patients are at higher risk for failure after definitive management and may benefit from intensified adjuvant therapy.
Comparison of Iodine Density Measurement Among Dual-Energy Computed Tomography Scanners From 3 Vendors
Authors: Kim Hyungjin , Goo Jin Mo , Kang Chang Kyung , Chae Kum Ju , Park Chang Min
Published: January 2018

Objectives

The aims of this study were to analyze the effect of dual-energy computed tomography (DECT) scanners and fluid characteristics on iodine quantification and to calculate the measurement variability range induced by those variables.

Methods

We performed an experimental phantom study with 4 mediastinal iodine phantoms. Each phantom contained 6 tubes of different iodine concentrations (0, 1.0, 2.5, 5.0, 10.0, and 20.0 mg/mL) diluted in a specific solvent, which was water, 10% amino acid solution, 20% lipid emulsion, or 18% calcium solution, respectively. Mediastinal phantoms were inserted into an anthropomorphic chest phantom and were scanned with 3 different DECT scanners from 3 vendors using 2 radiation dosage settings. Iodine density (IoD) and computed tomography (CT) attenuation at virtual monoenergetic 70-keV images and virtual nonenhanced images were measured for the iodine phantoms. The effects of DECT scanners, solvents, and radiation dosage on the absolute measurement error of IoD and on the CT attenuation profiles were investigated using linear mixed-effects models. Measurement variability range of IoD was also determined.

Results

Absolute error of IoD was not significantly affected by the DECT systems, kind of solvents, and radiation dosage settings. However, CT attenuation profiles were significantly different among the DECT vendors and simulated body fluids. Measurement variability range of IoD was from −0.6 to 0.4 mg/mL for the true iodine concentration 0 mg/mL.

Conclusions

Dual-energy CT systems and fluid characteristics did not have a significant effect on the IoD measurement accuracy. A cutoff of IoD for the determination of a truly enhancing lesion on DECT would be 0.4 mg/mL.
Has Abe's Womanomics Worked?
Authors: Nagase Nobuko
Published: January 2018

The present paper estimates the effect of the Abe Cabinet's Womanomics policies that aimed to increase female labor supply and keep women on a career path. The policies are surveyed, and the effects are estimated using microdata from the Labor Force Survey combined with data at the prefectural level on day care provision. A difference‐in‐difference (DD) method is applied to uncover the impacts of the Abe Cabinet's policies. The rapid increase in the provision of infant care, especially in the urban area, has contributed to a strong increase in the labor participation of mothers with young children. In addition, DD method estimates show a strong increase in mothers with infants staying in permanent‐contract regular employment. A significant shortening of work hours of workers, especially of parents with infants, is observed, which enabled working mothers to maintain their employment status. A change in the gender wage gap in the Japanese labor market is observed, but much progress is still required to close the large wage gap.
Combined thoracic paravertebral and pectoral nerve blocks for breast surgery under sedation: a prospective observational case series
Authors: Pawa A. , Wight J. , Onwochei D. N. , Vargulescu R. , Reed I. , Chrisman L. , Pushpanathan E. , Kothari A. , El‐Boghdadly K.
Published: January 2018

Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice. There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes. We conducted a prospective observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique, patient acceptability and surgeon satisfaction. Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia, with one conversion to general anaesthesia. Eleven out of 16 cases required low‐dose intra‐operative opioid analgesia. Out of the 15 surgical procedures completed under regional anaesthesia with sedation, all patients experienced either no or minimal intra‐operative pain, and all would choose this anaesthetic technique again. Surgeon‐reported operating conditions were ‘indistinguishable from general anaesthesia’ in most cases, and surgeons were ‘extremely satisfied’ or ‘satisfied’ with the technique after every procedure. Combined thoracic paravertebral plus pectoral nerve block with intra‐operative sedation is a feasible technique for breast surgery.
The Prevalence of Cannabinoid Hyperemesis Syndrome Among Regular Marijuana Smokers in an Urban Public Hospital
Authors: Habboushe Joseph , Rubin Ada , Liu Haoming , Hoffman Robert S.
Published: January 2018

Epidemiological data, including prevalence, for cannabinoid hyperemesis syndrome (CHS) remain largely unknown. Without these data, clinicians often describe CHS as ‘rare’ or ‘very rare’ without supporting evidence. We seek to estimate the prevalence of CHS in a population of patients presenting to a socio‐economically and racially diverse urban Emergency Department of a public hospital. This study consisted of a questionnaire administered to a convenience sample of patients presenting to the ED of the oldest public hospital in the United States. Trained Research Associates (RAs) administered the questionnaire to patients between the ages of 18–49 years who reported smoking marijuana at least 20 days per month. The survey included questions related to CHS symptoms (nausea and vomiting) and Likert scale rankings on eleven symptom relief methods, including ‘hot showers’. Patients were classified as experiencing a phenomenon consistent with CHS if they reported smoking marijuana at least 20 days per month and also rated ‘hot showers’ as five or more on the ten‐point symptom relief method Likert scale for nausea and vomiting. Among 2127 patients approached for participation, 155 met inclusion criteria as smoking 20 or more days per month. Among those surveyed, 32.9% (95% CI, 25.5–40.3%) met our criteria for having experienced CHS. If this is extractable to the general population, approximately 2.75 million (2.13–3.38 million) Americans may suffer annually from a phenomenon similar to CHS.
LAIR-1 shedding from human fibroblast-like synoviocytes in rheumatoid arthritis following TNF-α stimulation
Authors: Zhang Y , Wang S , Dong H , Yi X , Zhang J , Liu X , Zhuang R , Ding Y
Published: January 2018

This study examined the expression of the inhibitory receptor, leucocyte-associated immunoglobulin (Ig)-like receptor-1 (LAIR-1) in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) patients to investigate its potential role in the modulation of inflammatory cytokines, matrix metalloproteinases (MMPs) and invasiveness of synoviocytes. LAIR-1 expression in synovial tissues from RA patients, osteoarthritis patients and healthy donors was analysed by immunohistochemistry. The membrane-bound form (mLAIR-1) was detected by flow cytometry. Factors involved in inflammation and MMP activity in FLS were analysed by quantitative polymerase chain reaction (qPCR). LAIR-1 expression was higher in the synovia of the RA patients than those of the osteoarthritis patients. Co-immunostaining of vimentin/LAIR-1 demonstrated that LAIR-1 was localized mainly in FLS in the RA patients. Surprisingly, primary FLS isolated from the RA patients had low levels of mLAIR-1 expression, with cytoplasmic distribution. The extracellular domain of LAIR-1 was shed from the cell surface in response to tumour necrosis factor (TNF)-α, and this process could be blocked by serine protease inhibitors. Additional experiments indicated that LAIR-1 over-expression reduced FLS invasion considerably, which reduced simultaneously the mRNA levels of interleukin (IL)-6, IL-8 and MMP-13 in the presence of TNF-α. Our study demonstrated that LAIR-1 is an anti-inflammatory molecule, and was up-regulated in FLS in the RA patients; however, cell-surface LAIR-1 could be shed from cells in the inflammatory microenvironment in RA. This may weaken the interaction of LAIR-1 with its ligand, thus reducing the anti-inflammatory effects of LAIR-1. These findings suggested that LAIR-1 may be an important factor involved in the mediation of the progressive joint destruction in RA.
Contact sensitization in dental technicians with occupational contact dermatitis. Data of the Information Network of Departments of Dermatology (IVDK) 2001–2015
Authors: Heratizadeh Annice , Werfel Thomas , Schubert Steffen , Geier Johannes ,   for the IVDK
Published: January 2018

Background

Dental technicians (DTs) are at increased risk for allergic contact sensitization.

Objectives

To assess the current spectrum of occupational sensitization in DTs with occupational contact dermatitis (OCD).

Methods

A retrospective analysis of Information Network of Departments of Dermatology patch test data from the years 2001–2015 concerning DTs with OCD was performed.

Results

Patients of the study group (226 DTs with OCD) were significantly more often diagnosed with allergic contact dermatitis (37.6% versus 18.5%; p = 0.0002) than patients of the control group (124 DTs without OCD). In the study group, positive reactions were most frequently observed to methacrylates and/or acrylates (n = 67). Of these, 61 patients showed positive reactions to at least one of the five most frequent allergens in this group, namely 2‐hydroxyethyl methacrylate, 2‐hydroxypropyl methacrylate, methyl methacrylate, ethyl methacrylate, and/or ethylene glycol dimethacrylate. In contrast, no positive reactions to diurethane dimethacrylate (DUDMA) occurred. Among allergens of the German Contact Dermatitis Research Group series ‘dental metals’, positive reactions were less frequent and were mainly to palladium chloride (n = 6).

Conclusions

The present data analysis showed that the sensitization spectrum and spectrum of cross‐reactivity are largely unchanged as compared with the 1990s. It can be concluded that test recommendations are still valid and useful, except for the methacrylate DUDMA, which could be omitted.
A vitamin B12 conjugate of exendin‐4 improves glucose tolerance without associated nausea or hypophagia in rodents
Authors: Mietlicki‐Baase Elizabeth G. , Liberini Claudia G. , Workinger Jayme L. , Bonaccorso Ron L. , Borner Tito , Reiner David J. , Koch‐Laskowski Kieran , McGrath Lauren E. , Lhamo Rinzin , Stein Lauren M. , De Jonghe Bart C. , Holz George G. , Roth Christian L. , Doyle Robert P. , Hayes Matthew R.
Published: January 2018

Aims

While pharmacological glucagon‐like peptide‐1 receptor (GLP‐1R) agonists are FDA‐approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 (B12) bound to the GLP‐1R agonist exendin‐4 (Ex4), which displays enhanced proteolytic stability and retention of GLP‐1R agonism. Here, we evaluate whether the conjugate (B12‐Ex4) can improve glucose tolerance without producing anorexia and malaise.

Materials and methods

We evaluated the effects of systemic B12‐Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice. To evaluate whether differences in the profile of effects of B12‐Ex4 vs unconjugated Ex4 are the result of altered CNS penetrance, rats received systemic injections of fluorescein‐Ex4 (Flex), Cy5‐B12 or Cy5‐B12‐Ex4 and brain penetrance was evaluated using confocal microscopy. Uptake of systemically administered Cy5‐B12‐Ex4 in insulin‐containing pancreatic beta cells was also examined.

Results

B12‐Ex4 conjugate improves glucose tolerance, but does not elicit the malaise and anorexia produced by unconjugated Ex4. While Flex robustly penetrates into the brain (dorsal vagal complex, paraventricular hypothalamus), Cy5‐B12 and Cy5‐B12‐Ex4 fluorescence were not observed centrally, supporting an absence of CNS penetrance, in line with observed reduction in CNS‐associated Ex4 side effects. Cy5‐B12‐Ex4 colocalizes with insulin in the pancreas, suggesting direct pancreatic action as a potential mechanism underlying the hypoglycaemic effects of B12‐Ex4.

Conclusion

These novel findings highlight the potential clinical utility of B12‐Ex4 conjugates as possible future T2DM therapeutics with reduced incidence of adverse effects.
Serum lipoprotein (a) predicts acute coronary syndromes in patients with severe carotid stenosis
Authors: Rigamonti Fabio , Carbone Federico , Montecucco Fabrizio , Bonaventura Aldo , Liberale Luca , Burger Fabienne , Roth Aline , Bertolotto Maria , Spinella Giovanni , Pane Bianca , Palombo Domenico , Pende Aldo , Dallegri Franco , Mach François , Bertolini Stefano , Pisciotta Livia
Published: January 2018

Background

Different cut‐off values of serum lipoprotein (a) [Lp (a)] were recently identified to better stratify cardiovascular risk categories. Both pathophysiological and prognostic values of Lp (a) remain unclear.

Materials and methods

Here, the prognostic value of Lp (a) and its correlation with intraplaque features were assessed in patients with severe carotid artery stenosis undergoing endarterectomy (n = 180). The cut‐off value of 10 mg/dL for serum Lp (a) was selected to predict 24‐month follow‐up acute coronary syndrome (ACS). In addition, the association between serum Lp (a) and intraplaque lipids, collagen, inflammatory and vascular cells was assessed. Serum Lp (a) levels were measured by nephelometric assay.

Results

Patients with high Lp (a) had similar comorbidities, medications and laboratory parameters as compared to low Lp (a) levels. At 24‐month follow‐up, patients with high Lp (a) had more ACS as compared to low levels. Histological parameters within plaques were comparable in the study groups. No significant correlation between Lp (a) serum levels and intraplaque parameters was found, except for a weak positive association with smooth muscle cells in upstream plaque portions. When adjusted for gender, the presence of dyslipidaemia and chronic coronary artery disease, Lp (a) ≥10 mg/dL remained predictive for ACS.

Conclusions

Lp (a) determination could be a useful tool to predict ACS in patients with severe carotid stenosis.
The effect of partially exposed connective tissue graft on root‐coverage outcomes: a systematic review and meta‐analysis
Authors: Dodge Austin , Garcia Jeffrey , Luepke Paul , Lai Yu‐Lin , Kassab Moawia , Lin Guo‐Hao
Published: January 2018

The aim of this systematic review was to compare the root‐coverage outcomes of using a partially exposed connective tissue graft (CTG) technique with a fully covered CTG technique for root coverage. An electronic search up to February 28th, 2017, was performed to identify human clinical studies with data comparing outcomes of root coverage using CTG, with and without a partially exposed graft. Five clinical studies were selected for inclusion in this review. For each study, the gain of keratinized gingiva, reduction of recession depth, number of surgical sites achieving complete root coverage, percentage of root coverage, gain of tissue thickness, and changes of probing depth and clinical attachment level were recorded. Meta‐analysis for the comparison of complete root coverage between the two techniques presented no statistically significant differences. A statistically significant gain of keratinized tissue in favor of the sites with an exposed CTG and a tendency of greater reduction in recession depth were seen at the sites with a fully covered CTG. Based on the results, the use of a partially exposed CTG in root‐coverage procedures could achieve greater gain in keratinized gingiva, while a fully covered CTG might be indicated for procedures aiming to reduce recession depth.
Hospital nurses’ information retrieval behaviours in relation to evidence based nursing: a literature review
Authors: Alving Berit Elisabeth , Christensen Janne Buck , Thrysøe Lars
Published: January 2018

Objective

The purpose of this literature review is to provide an overview of the information retrieval behaviour of clinical nurses, in terms of the use of databases and other information resources and their frequency of use.

Methods

Systematic searches carried out in five databases and handsearching were used to identify the studies from 2010 to 2016, with a populations, exposures and outcomes (PEO) search strategy, focusing on the question: In which databases or other information resources do hospital nurses search for evidence based information, and how often?

Results

Of 5272 titles retrieved based on the search strategy, only nine studies fulfilled the criteria for inclusion. The studies are from the United States, Canada, Taiwan and Nigeria. The results show that hospital nurses’ primary choice of source for evidence based information is Google and peers, while bibliographic databases such as PubMed are secondary choices. Data on frequency are only included in four of the studies, and data are heterogenous.

Conclusions

The reasons for choosing Google and peers are primarily lack of time; lack of information; lack of retrieval skills; or lack of training in database searching. Only a few studies are published on clinical nurses’ retrieval behaviours, and more studies are needed from Europe and Australia.
Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells
Authors: Sasidharan Nair Varun , Elkord Eyad
Published: January 2018

Regulatory T cells (Tregs) play essential roles in immune homeostasis; however, their role in tumor microenvironment (TME) is not completely evident. Several studies reported that infiltration of Tregs into various tumor tissues promotes tumor progression by limiting antitumor immunity and supporting tumor immune evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells expressing different immunosuppressive molecules favoring tumor progression. For an effective cancer therapy, it is critical to understand the Treg heterogeneity and biology in the TME. Recent studies have shown that immune checkpoint molecules promote cancer progression through various antitumor inhibitory mechanisms. Recent advances in cancer immunotherapy have shown the promising potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune responses and clinical benefits in patients with cancer at late stages. Most studies revealed the effect of ICIs on T effector cells, and little is known about their effect on Tregs. In this review, we highlight the effects of the ICIs, including anti‐CTLA‐4, anti‐PD‐1/PD‐L1, anti‐LAG‐3, anti‐TIM‐3, and anti‐TIGIT, on tumor‐infiltrating and peripheral Tregs to elicit effector T‐cell functions against tumors. Additionally, we discuss how ICIs may target Tregs for cancer immunotherapy.
Distinct effect of age, sex, and CMV seropositivity on dendritic cells and monocytes in human blood
Authors: Puissant‐Lubrano Bénédicte , Apoil Pol André , Guedj Kevin , Congy‐Jolivet Nicolas , Roubinet Francis , Guyonnet Sophie , Sourdet Sandrine , Nourhashemi Fati , Blancher Antoine
Published: January 2018

We analyzed the impact of age, sex, and CMV on blood monocyte and dendritic cell (DC) subpopulations in 256 healthy individuals aged from 19 to 96 years. Flow cytometry was performed on whole blood within the 4 h following blood drawing. Myeloid (mDC) and plasmacytoid DC (pDC), classical, intermediate, and nonclassical monocytes were enumerated by means of TruCount tubes (BD Biosciences). We provided reference values for mDC, pDC and the three monocyte subpopulations. The numbers of classical, intermediate, and nonclassical monocytes slightly increased with age while the numbers of mDC and pDC did not vary significantly. The level of expression of CD64 and CD163 on monocytes significantly increased with age while HLA‐DR expression did not vary significantly. More precisely, CD163 expression level on intermediate monocyte slightly increased with age in women only (Spearman P = 0.019) while CD64 expression increased on monocytes in CMV‐positive individuals only. We observed that sex had almost no impact on the numbers of monocytes and DC and on their expression level of CD64 and HLA‐DR. We observed a significant decrease in the numbers of pDC with age in CMV‐positive individuals, but not in CMV negative individuals. This suggests that the lifelong subclinical infection by CMV could influence the number of circulating DC of lymphoid origin. In contrast, CMV serostatus had no significant impact on absolute numbers of mDC and monocytes.
Superior properties of CellTrace Yellow™ as a division tracking dye for human and murine lymphocytes
Authors: Tempany Jessica C , Zhou Jie HS , Hodgkin Philip D , Bryant Vanessa L
Published: January 2018

The discovery of cell division tracking properties of 5‐(and‐6)‐carboxyfluorescein diacetate succinimidyl ester (CFSE) by Lyons and Parish in 1994 led to a broad range of new methods and numerous important biological discoveries. After labeling, CFSE is attached to free amine groups and intracellular proteins in the cytoplasm and nucleus of a cell, and halves in fluorescence intensity with each round of cell division, enabling enumeration of the number of divisions a cell has undergone. A range of popular division tracking dyes were subsequently developed, including CellTrace Violet (CTV), making available the green fluorescent channel previously occupied by CFSE. More recently, CellTrace Yellow (CTY) and CellTrace Far Red (CTFR), each with unique fluorescence properties, were introduced. In a comparison, we found that the fluorescence values of both dyes were well separated from autofluorescence, and enabled a greater number of divisions to be identified than CTV, before this limit was reached. These new dyes provided clear and well‐separated peaks for both murine and human B lymphocytes, and should find wide application. The range of excitation/emission spectra available for division tracking dyes now also facilitates multiplexing, that is, the labeling of cells with different combinations of dyes to give a unique fluorescence signature, allowing single cell in vitro and in vivo tracking. The combinatorial possibilities are significantly increased with these additional dyes.
GPR65 inhibits experimental autoimmune encephalomyelitis through CD4+ T cell independent mechanisms that include effects on iNKT cells
Authors: Wirasinha Rushika C , Vijayan Dipti , Smith Nicola J , Parnell Grant P , Swarbrick Alexander , Brink Robert , King Cecile , Stewart Graeme , Booth David R , Batten Marcel
Published: January 2018

The G protein‐coupled receptor 65 (GPR65) gene has been genetically associated with several autoimmune diseases, including multiple sclerosis (MS). GPR65 is predominantly expressed in lymphoid organs and is activated by extracellular protons. In this study, we tested whether GPR65 plays a functional role in demyelinating autoimmune disease. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we found that Gpr65‐deficient mice develop exacerbated disease. CD4+ helper T cells are key drivers of EAE pathogenesis, however, Gpr65 deficiency in these cells did not contribute to the observed exacerbated disease. Instead, Gpr65 expression levels were found to be highest on invariant natural killer T (iNKT) cells. EAE severity in Gpr65‐deficient mice was normalized in the absence of iNKT cells (CD1d‐deficient mice), suggesting that GPR65 signals in iNKT cells are important for suppressing autoimmune disease. These findings provide functional support for the genetic association of GPR65 with MS and demonstrate GPR65 signals suppress autoimmune activity in EAE.
Additive centralized and Stackelberg DEA models for two‐stage system with shared resources
Authors: Ma Jianfeng , Qi Linan , Deng Lizhi
Published: January 2018

Data envelopment analysis (DEA) is a nonparametric programming method for evaluating the efficiency performance of decision making units (DMUs) with multiple inputs and outputs. The classic DEA model cannot provide accurate efficiency measurement and inefficiency sources of DMUs with complex internal structure. The network DEA approach opens the “black box” of DMU by taking its internal operations into consideration. The complexities of DMU's internal structure involve not only the organization of substages, but also the inputs allocation and the operational relations among the individual stages. This paper proposes a set of additive DEA models to evaluate and decompose the efficiency of a two‐stage system with shared inputs and operating in cooperative and Stackelberg game situations. Under the assumptions of cooperative and noncooperative gaming, the proposed models are able to highlight the effects of strategic elements on the efficiency formation of DMUs by calculating the optimal proportion of the shared inputs allocated to each stage. The case of information technology in the banking industry at the firm level, as discussed by Wang, is revisited using the developed DEA approach.
Let's get cynical about this! Recursive relationships between psychological contract breach and counterproductive work behaviour
Authors: Griep Yannick , Vantilborgh Tim
Published: January 2018

Although counterproductive work behaviour towards the organization (CWB‐O) or supervisors (CWB‐S) is commonly treated as a reaction to psychological contract breach (PCB), we propose that the PCB‐CWB relationship is recursive and that CWB may increase the likelihood to perceive PCB through its effects on self‐esteem and subsequently on organizational cynicism. By estimating a two‐level time‐lagged mediation model on daily data from 103 US employees (904 observations), we found evidence for this hypothesized chain of events. These findings demonstrate that PCB and CWB happen with reference to past perceptions of PCB and/or CWB and future anticipations of PCB and/or CWB. We discuss suggestions for future research and novel practical implications in preventing further escalation.

Practitioner points

When employees perceive that their organization has breached its obligations, employees are likely to retaliate by engaging in acts of CWB‐O and CWB‐S.

Employees are likely to suffer from reduced self‐esteem and increased cynicism when they have engaged in CWB‐S following a PC breach.

When employees become more cynical, they are more likely to perceive future PC breaches.

Based on the reciprocal nature of our findings, this study highlights the need to update existing theories, as well as indicates the need for swift interventions in the aftermath of PC breach and enactment of CWB.
Differential effects of experimental hyperthyroidism on declined immunity of broiler chicken
Authors: Khilji M. S. , Sandhu M. A. , Yousaf M. S. , Saeed A. A. , Rehman H. U. , Zaneb H. , Rashid M. A.
Published: January 2018

Thyroid hormones (THs) are involved in the development of lymphoid organs and regulation of immune function in birds. However, their role as an immune‐modulator in the hyperthyroid state is still debatable. To explore the interrelationship of thyroxine (T4) and the immune system, chicks were divided into three groups. Group I was comprised of control birds, who received the basal diet while group II and III were given diets supplemented with 5 μg and 10 μg thyroxine/kg feed, respectively, from 15 to 28 days of age. Cell‐mediated immune response was evaluated through in vitro abdominal macrophage phagocytosis assay, macrophage nitric oxide (NO) production, heterophil‐to‐lymphocyte (H:L) ratio and delayed‐type hypersensitivity response against phytohemagglutinin (PHA). Humoural immune response was assessed through serum IgG and IgM antibody production against sheep red blood cells (SRBCs) and antibody production against infectious bronchitis virus (IBV). Sampling was carried out at 7, 14 and 21 days of treatment. Results have shown higher levels (p < .001) of circulating T4 in both treatment groups compared to the control group. There was a lower (p < .05) macrophage engulfment percentage, an increase in H:L ratio (p < .001) in treated birds, while their NO production remained higher (p < .05) in thyroxine supplemented groups after bacterial lipopolysaccharide stimulation. The humoural immune response revealed a significant decline (p < .001) in IgG, IgM antibody production against SRBCs but IBV circulating antibodies increased with age. In conclusion, hyperthyroidism has a strong co‐relation with decreased immune performance of birds.