bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening methods for obstructive sleep apnoea in severely obese pregnant women
Authors: Longworth H. , McCallin K. , Narayanan R. P. , Turner M. A. , Quenby S. , Rycroft D. , Charnley M. , Abayomi J. , Topping J. , Weeks A. D. , Wilding J. P. H.
Published: May 2017

Obstructive sleep apnoea (OSA) is an often‐overlooked diagnosis, more prevalent in the obese population. Screening method accuracy, uptake and hence diagnosis is variable. There is limited data available regarding the obese pregnant population; however, many studies highlight potential risks of apnoeic episodes to mother and foetus, including hypertension, diabetes and preeclampsia. A total of 162 women with a body mass index (BMI) ≥ 35 were recruited from a tertiary referral hospital in the northwest of England. They were invited to attend three research antenatal clinics, completing an Epworth Sleepiness Scale (ESS) questionnaire at each visit. A monitor measuring the apnoea hypopnoea index (AHI) was offered at the second visit. Data taken from consent forms, hospital notes and hospital computer records were collated and anonymized prior to statistical analysis. A total of 12.1% of women had an ESS score of >10, suggesting possible OSA. Rates increased throughout pregnancy, although unfortunately, the attrition rate was high; 29.0% of women used the RUSleeping (RUS) meter, and only one (2.1%) met pre‐specified criteria for OSA (AHI ≥ 15). This individual had OSA categorized as severe and underwent investigations for preeclampsia, eventually delivering by emergency caesarean section due to foetal distress. The accuracy of the ESS questionnaire, particularly the RUS monitor, to screen for OSA in the pregnant population remains unclear. Further research on a larger sample size using more user‐friendly technology to confidently measure AHI would be beneficial. There are currently no guidelines regarding screening for OSA in the obese pregnant population, yet risks to both mother and foetus are well researched.
Sensitization and cross‐reactivity patterns of contact allergy to diisocyanates and corresponding amines: investigation of diphenylmethane‐4,4′‐diisocyanate, diphenylmethane‐4,4′‐diamine, dicyclohexylmethane‐4,4′‐diisocyanate, and dicylohexylmethane‐4,4′‐diamine
Authors: Hamada Haneen , Bruze Magnus , Zimerson Erik , Isaksson Marléne , Engfeldt Malin
Published: May 2017

Background

Isocyanates are used in polyurethane production. Dermal exposure to isocyanates can induce contact allergy. The most common isocyanate is diphenylmethane diisocyanate used for industrial purposes. The isomer diphenylmethane‐4,4′‐diisocyanate (4,4′‐MDI) is used in patch testing. Diphenylmethane‐4,4′‐diamine (4,4′‐MDA) is its corresponding amine. Concurrent reactions to 4,4′‐MDI and 4,4′‐MDA have been reported, as have concurrent reactions to 4,4′‐MDI and dicyclohexylmethane‐4,4′‐diisocyanate (4,4′‐DMDI).

Objectives

To investigate the sensitization capacities and the cross‐reactivity of 4,4′‐MDI, 4,4′‐MDA, 4,4′‐DMDI, and dicyclohexylmethane‐4,4′‐diamine (4,4′‐DMDA).

Methods

The guinea‐pig maximization test (GPMT) was used.

Results

The GPMT showed sensitizing capacities for all investigated substances: 4,4′‐MDI, 4,4′‐MDA, 4,4′‐DMDI, and 4,4′‐DMDA (all p < 0.001). 4,4′‐MDI‐sensitized animals showed cross‐reactivity to 4,4′‐MDA (p < 0.001) and 4,4′‐DMDI (all p < 0.05). 4,4′‐MDA‐sensitized animals showed cross‐reactivity to 4,4′‐DMDA (p = 0.008).

Conclusion

All of the investigated substances were shown to be strong sensitizers. Animals sensitized to 4,4′‐MDI showed cross‐reactivity to 4,4′‐MDA and 4,4′‐DMDI, supporting previous findings in the literature. The aromatic amine 4,4′‐MDA showed cross‐reactivity to the aliphatic amine 4,4′‐DMDA.
Latent developmental trajectories of episodic heavy drinking from adolescence to early adulthood: Predictors of trajectory groups and alcohol problems in early adulthood as outcome
Authors: Brunborg Geir Scott , Norström Thor , Storvoll Elisabet E.
Published: May 2017

Introduction and Aims. To identify latent developmental episodic heavy drinking (EHD) trajectory groups for Norwegian adolescents, investigate risk factors associated with group membership and to assess differences in alcohol problems between different groups in early adulthood. Design and Methods. Data were from 1266 individuals measured at four time points from age 13/14 years to age 26/27 years. Latent class growth analysis was used to identify groups with different EHD development. Multinomial logistic regression was used to investigated if gender, impulsivity, school commitment, parents' socio‐economic status, frequency of seeing parents drunk and parental knowledge could predict group membership. Differences in alcohol problem scores at age 26/27 were also assessed. Results. Four trajectory groups were identified: ‘stable high’, ‘early increasers’, ‘late increasers’ and ‘stable low’. Membership of the high‐risk trajectory groups ‘stable high’ and ‘early increasers’ was predicted by high impulsivity, low school commitment, high frequency of seeing parents drunk and low parental knowledge. The risk of alcohol problems at age 26/27 was greater for the ‘stable high’ group, the ‘early increasers’ and the ‘late increasers’ compared with the ‘stable low’ group. The ‘stable high’ and ‘early increasers’ had similar risk of alcohol problems. Discussion and Conclusions. Stable high and early increasing EHD in adolescence was associated with more alcohol problems in early adulthood. Such trajectories were predicted by high impulsivity, low school commitment, high frequency of seeing parents drunk and low parental knowledge. [Brunborg GS, Norström T, Storvoll EE. Latent developmental trajectories of episodic heavy drinking from adolescence to early adulthood: Predictors of trajectory groups and alcohol problems in early adulthood as outcome.
Development and psychometric properties of the Hand‐Use‐at‐Home questionnaire to assess amount of affected hand‐use in children with unilateral paresis
Authors: Geerdink Yvonne , Aarts Pauline , van der Holst Menno , Lindeboom Robert , Van Der Burg Jan , Steenbergen Bert , Geurts Alexander C
Published: May 2017

Aim

To describe the development of the parent‐rated Hand‐Use‐at‐Home questionnaire (HUH) assessing the amount of spontaneous use of the affected hand in children with unilateral paresis, and to test its internal structure, unidimensionality, and validity.

Method

Parents of children with unilateral cerebral palsy (CP) and professionals participated in the development of the HUH. To examine internal validity, data of 322 children (158 males, 164 females; mean age 6y 7mo, standard deviation [SD] 2y 1mo) with unilateral CP (n=131) or neonatal brachial plexus palsy (NBPP) (n=191) were collected. Rasch analysis was used to examine discriminative capacity of the 5‐category rating scale as well as unidimensionality and hierarchy of the item set. Additionally, data of 55 children with typical development (24 males, 31 females; 6y 9mo, SD 2y 5mo) were used to examine construct validity.

Results

The 5‐category rating scale was disordered in all items and was collapsed to obtain the best discriminating sum score. Ten misfitting or redundant items were removed. Eighteen hierarchically ordered bimanual items fitted the unidimensional model within acceptable range. The HUH significantly discriminated between the three groups (children with typical development, NBPP, unilateral CP; H(2)=118.985, p<0.001), supporting its construct validity.

Interpretation

The HUH is a valid instrument to assess the amount of spontaneous use of the affected hand in children with unilateral upper‐limb paresis.
Challenges describing motor profiles in alternating hemiplegia of childhood
Authors: Alderson Lucy
Published: May 2017

This commentary is on the original article by Masoud et al. on pages 822–828 of this issue.
Effects of MetAP2 inhibition on hyperphagia and body weight in Prader–Willi syndrome: A randomized, double‐blind, placebo‐controlled trial
Authors: McCandless Shawn E. , Yanovski Jack A. , Miller Jennifer , Fu Cary , Bird Lynne M. , Salehi Parisa , Chan Christine L. , Stafford Diane , Abuzzahab M. Jennifer , Viskochil David , Barlow Sarah E. , Angulo Moris , Myers Susan E. , Whitman Barbara Y. , Styne Dennis , Roof Elizabeth , Dykens Elisabeth M. , Scheimann Ann O. , Malloy Jaret , Zhuang Dongliang , Taylor Kristin , Hughes Thomas E. , Kim Dennis D. , Butler Merlin G.
Published: May 2017

Aims

There are no treatments for the extreme hyperphagia and obesity in Prader–Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib.

Materials and Methods

Participants with PWS (12‐65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co‐primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ‐CT); possible score 0‐36] and weight by intention‐to‐treat. ClinicalTrials.gov registration: NCT02179151.

Results

One‐hundred and seven participants were included in the intention‐to‐treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ‐CT total score was greater in the 1.8 mg (mean difference −6.3, 95% CI −9.6 to −3.0;
P
= .0003) and 2.4 mg beloranib groups (−7.0, 95% CI −10.5 to −3.6;
P
= .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference − 8.2%, 95% CI −10.8 to −5.6;
P
< .0001) and 2.4 mg beloranib (−9.5%, 95% CI −12.1 to −6.8;
P
< .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib‐treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo.

Conclusions

MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia‐related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.
Isolation and identification of endophytic bacteria with plant growth promoting and biocontrol potential from oak trees
Authors: Tashi‐Oshnoei F. , Harighi B. , Abdollahzadeh J.
Published: May 2017

Samples of roots, leaves and stems of healthy oak trees were collected from various locations in the Baneh and Marivan regions, Iran. In total, 63 endophytic bacteria were isolated and grouped according to phenotypic properties. Seven selected isolates were further identified by partial sequencing of the 16S rRNA gene. Isolates Pp54, Pp88, Pp95 and Pp177 were Pseudomonas spp., isolates Sm59 and Sm79 were Stenotrophomonas spp., and isolate Bf 172 was a Bacillus sp. The ability of these isolates for plant hormone production such as auxin and gibberellin was evaluated, along with siderophore production, phosphate solubilization, atmospheric nitrogen fixation, protease and hydrogen cyanide production. All strains produced auxin and gibberellin in different amounts. Atmospheric nitrogen fixation ability was positive for strains Sm79, Pp54, Pp88 and Pp95. All strains except Sm79 solubilized phosphate. Strains Sm59, SM79, Pp88, Pp177 and Bf172 produced protease. Pp88, Pp95, Bf172 and Pp177 were able to produce siderophore. Strains Sm79 and Pp95 released low concentrations of hydrogen cyanide. Amongst the strains tested, Pp95, Pp88, Pp177 and Sm79 had different inhibitory effects on the bacterial plant pathogen, Pseudomonas syringae pv. syringae under in vitro conditions. This is the first reported case of endophytic Bacillus, Pseudomonas and Stenotrophomonas strains from oak trees in Iran.
Mortgage Debt and the Social Function of Contract
Authors: Domurath Irina
Published: May 2017

The high numbers of over‐indebtedness and of evictions in Europe since the financial crisis have highlighted the need to re‐think the role that mortgage credit plays for societies. This contribution examines the social function of contract law, based on the observation that contract law is a means of allocating welfare in a political economy in which the welfare state is in retreat. The claim asserted in this article is that EU law in the field of mortgages does not fulfil its social function because it is based on a formalistic understanding of contract law. In order to close the protective gap brought about by a shift in the allocation of welfare from public provision to private markets without altering the understanding of contracts, the proposal is to follow the cooperative contract model of contracts as social cooperation. This approach allows for an assessment of fairness that acknowledges the long‐term character of mortgage contracts and the ensuing need to distribute market risks between both contracting parties.
Has Euro Area Monetary Policy Become Redistribution by Monetary Means? ‘Unconventional’ Monetary Policy as a Hidden Transfer Mechanism
Authors: Tuori Klaus
Published: May 2017

This article takes an unconventional perspective on Eurosystem monetary policy by asking what kind of redistributive effects it might have had. Any monetary policy can have redistributive effects as it alters the environment in which economic agents, households and companies, operate. Some benefit and some stand to lose from decisions by the central bank. However, monetary policy generally does not aim at redistributive implications; indeed, in the Euro area context it does not have a mandate to do so. Against this background it is not irrelevant how the large number of Eurosystem monetary policy measures during crises should be assessed. The article claims that in particular the government bond purchase programmes by the Eurosystem and massive liquidity support to banks could have had redistributive elements even in a prominent role. The Eurosystem has become the final guarantor of Member States in trouble and their banking sectors, even reinforcing the link between the two. This focus has potentially pushed the Eurosystem to neglect its primary objective but also its broader implications for the Euro area economy and societies more generally.
Multi‐scale responses to warming in an experimental insect metacommunity
Authors: Grainger Tess Nahanni , Gilbert Benjamin
Published: May 2017

In metacommunities, diversity is the product of species interactions at the local scale and dispersal between habitat patches at the regional scale. Although warming can alter both species interactions and dispersal, the combined effects of warming on these two processes remains uncertain. To determine the independent and interactive effects of warming‐induced changes to local species interactions and dispersal, we constructed experimental metacommunities consisting of enclosed milkweed patches seeded with five herbivorous milkweed specialist insect species. We treated metacommunities with two levels of warming (unwarmed and warmed) and three levels of connectivity (isolated, low connectivity, high connectivity). Based on metabolic theory, we predicted that if plant resources were limited, warming would accelerate resource drawdown, causing local insect declines and increasing both insect dispersal and the importance of connectivity to neighboring patches for insect persistence. Conversely, given abundant resources, warming could have positive local effects on insects, and the risk of traversing a corridor to reach a neighboring patch could outweigh the benefits of additional resources. We found support for the latter scenario. Neither resource drawdown nor the weak insect‐insect associations in our system were affected by warming, and most insect species did better locally in warmed conditions and had dispersal responses that were unchanged or indirectly affected by warming. Dispersal across the matrix posed a species‐specific risk that led to declines in two species in connected metacommunities. Combined, this scaled up to cause an interactive effect of warming and connectivity on diversity, with unwarmed metacommunities with low connectivity incurring the most rapid declines in diversity. Overall, this study demonstrates the importance of integrating the complex outcomes of species interactions and spatial structure in understanding community response to climate change.
A global geography of synchrony for marine phytoplankton
Authors: Defriez Emma J. , Reuman Daniel C.
Published: May 2017

Aim

Spatial synchrony in plankton is imperfectly understood yet may have far‐reaching implications, for example for carbon export to the deep ocean. Several techniques have been used to describe patterns of spatial synchrony, from correlation coefficients to spectral methods. Some studies have used temporally extensive data sets to identify causes of synchrony. This study instead uses the exceptional spatial extent provided by remotely sensed data to describe, for the first time as far as we know, geographical patterns of synchrony in marine phytoplankton. We use these patterns to illuminate drivers of synchrony and of its geography.

Location

The oceans.

Time period

2003–2015.

Major taxon

Chlorophyll a‐containing phytoplankton.

Methods

Synchrony in chlorophyll a concentrations is mapped globally. Spatial statistics and model selection are used to illuminate main statistical determinants of synchrony and of geographical patterns in synchrony.

Results

The first main result is that there is a pronounced and previously unmapped geography of synchrony for phytoplankton. For instance, synchrony was highest in the open ocean, specifically in gyres, and lowest in coastal regions. Spatial modelling provided the second main result that synchrony in sea surface temperature (SST) was a major statistical determinant of chlorophyll synchrony in both the Pacific and Atlantic Oceans, indicating a strong Moran effect, although possibly an indirect and/or complex one. In the Pacific Ocean, this effect depended on the time‐scales on which synchrony was assessed, providing our third result, which is that synchrony of phytoplankton and its geography can be time‐scale specific. Synchrony of surface solar irradiance was not associated with synchrony of chlorophyll.

Main conclusions

To our knowledge, this study is the first to map geography of synchrony in marine plankton. We showed that this geography is pronounced. Geographical patterns illuminated determinants of synchrony. The geography of synchrony is a major phenomenon that has been little explored.
In vitro site‐specific recombination mediated by the tyrosine recombinase XerA of Thermoplasma acidophilum
Authors: Jo Minji , Murayama Yasuto , Tsutsui Yasuhiro , Iwasaki Hiroshi
Published: May 2017

In organisms with circular chromosomes, such as bacteria and archaea, an odd number of homologous recombination events can generate a chromosome dimer. Such chromosome dimers cannot be segregated unless they are converted to monomers before cell division. In Escherichia coli, dimer‐to‐monomer conversion is mediated by the paralogous XerC and XerD recombinases at a specific dif site in the replication termination region. Dimer resolution requires the highly conserved cell division protein/chromosome translocase FtsK, and this site‐specific chromosome resolution system is present or predicted in most bacteria. However, most archaea have only XerA, a homologue of the bacterial XerC/D proteins, but no homologues of FtsK. In addition, the molecular mechanism of XerA‐mediated chromosome resolution in archaea has been less thoroughly elucidated than those of the corresponding bacterial systems. In this study, we identified two XerA‐binding sites (dif1 and dif2) in the Thermoplasma acidophilum chromosome. In vitro site‐specific recombination assays showed that dif2, but not dif1, serves as a target site for XerA‐mediated chromosome resolution. Mutational analysis indicated that not only the core consensus sequence of dif2, but also its flanking regions play important roles in the recognition and recombination reactions mediated by XerA.
Gender violence, poverty and HIV infection risk among persons engaged in the sex industry: cross‐national analysis of the political economy of sex markets in 30 European and Central Asian countries
Authors: Reeves A , Steele S , Stuckler D , McKee M , Amato‐Gauci A , Semenza JC
Published: May 2017

Objectives

Persons engaged in the sex industry are at greater risk of HIV and other sexually transmitted infections than the general population. One major factor is exposure to higher levels of risky sexual activity. Expanding condom use is a critical prevention strategy, but this requires negotiation with those buying sex, which takes place in the context of cultural and economic constraints. Impoverished individuals who fear violence are more likely to forego condoms.

Methods

Here we tested the hypotheses that poverty and fear of violence are two structural drivers of HIV infection risk in the sex industry. Using data from the European Centre for Disease Prevention and Control and the World Bank for 30 countries, we evaluated poverty, measured using the average income per day per person in the bottom 40% of the income distribution, and gender violence, measured using homicide rates in women and the proportion of women exposed to violence in the last 12 months and/or since age 16 years.

Results

We found that HIV prevalence among those in the sex industry was higher in countries where there were greater female homicide rates (β = 0.86; P = 0.018) and there was some evidence that self‐reported exposure to violence was also associated with higher HIV prevalence (β = 1.37; P = 0.043). Conversely, HIV prevalence was lower in countries where average incomes among the poorest were greater (β = −1.05; P = 0.046).

Conclusions

Our results are consistent with the theory that reducing poverty and exposure to violence may help reduce HIV infection risk among persons engaged in the sex industry.
Jingle bells or ‘green’ bells? The impact of socially responsible consumption principles upon consumer behaviour at Christmas time
Authors: Robinot Élisabeth , Ertz Myriam , Durif Fabien
Published: May 2017

Socially responsible consumption (SRC) behaviours have progressed over the last few years and appear to show signs of a lasting trend. Situations of atypical consumption such as Christmas time, however, raise an important and as of yet unexplored question: What are the influences of unusual situations upon the relationship between people's socially responsible profile and their socially responsible purchase intentions (SRPI)? The objective of this article is thus to use the theory of planned behaviour (Ajzen, ) and environment‐based variables, called ‘atmospherics’, to answer to this question. A Web survey on a total sample of 301 Canadian consumers, shows that people's past SRC behaviours are positively related to their SRPI in unusual situations. Moreover, the atmosphere of the place consumers are situated in has a negative moderating influence upon this relationship. This result is explained by a change in people's attitude toward SRC. However, this negative moderating effect of atmosphere is contained and constrained by social desirability in the form of subjective norms on SRC and the level of behavioural control consumers perceive.
Men Doing and Undoing Gender at Work: A Review and Research Agenda
Authors: Kelan Elisabeth K.
Published: May 2017

While research on gender in organizations has not only documented sustained gender inequality, it has also offered an understanding of how gender is enacted through doing and undoing gender. An underexplored aspect concerns how men can do and undo gender to support or hinder gender equality processes in organizations. Doing gender is then understood as creating gender difference while undoing gender would conversely mean to reduce gender difference. The former is supporting gender inequality while the latter means moving toward gender equality. This article therefore provides a systematic review of empirical articles that discuss how men are doing and undoing gender within an organizational context. It is shown that undoing gender practices of men in organizations are under‐researched and a research agenda of how men can undo gender at work is thus developed. This article makes a two‐fold contribution: first it offers a refinement of doing and undoing gender approaches and second, it develops a research agenda for exploring how men can undo gender at work.
Lung‐resident γδ T cells and their roles in lung diseases
Authors: Cheng Min , Hu Shilian
Published: May 2017

γδ T cells are greatly enriched in mucosal and epithelial sites, such as the skin, respiratory, digestive and reproductive tracts, and they are defined as tissue‐resident immune cells. In these tissues, the characteristics and biological roles of γδ T cells are distinguished from each other. The lungs represent the most challenging immunological dilemma for the host, and they have their own effective immune system. The abundance of γδ T cells, an estimated 8–20% of resident pulmonary lymphocytes in the lung, maintains lung tissue homeostasis. In this review, we summarize the recent research progress regarding lung‐resident γδ T cells, including their development, residency and immune characteristics, and discuss the involvement of γδ T cells in infectious diseases of the lung, including bacterial, viral and fungal infections; lung allergic disease; lung inflammation and fibrosis; and lung cancer.
Intestinal dysbiosis and probiotic applications in autoimmune diseases
Authors: de Oliveira Gislane Lelis Vilela , Leite Aline Zazeri , Higuchi Bruna Stevanato , Gonzaga Marina Ignácio , Mariano Vânia Sammartino
Published: May 2017

In humans, a complex interaction between the host immune system and commensal microbiota is required to maintain gut homeostasis. In this symbiotic relationship, the microbiota provides carbohydrate fermentation and digestion, vitamin synthesis and gut‐associated lymphoid tissue development, as well as preventing colonization by pathobionts, whereas the host offers a niche and nutrients for the survival of the microbiota. However, when this mutualistic relationship is compromised and an altered interaction between immune cells and microorganisms occurs, the gut microbiota may cause or contribute to the establishment of infectious diseases and trigger autoimmune diseases. Researchers have made efforts to clarify the role of the microbiota in autoimmune disease development and find new therapeutic approaches to treat immune‐mediated diseases. However, the exact mechanisms involved in the dysbiosis and breakdown of the gut epithelial barrier are currently unknown. Here, we provide a general overview of studies describing gut microbiota perturbations in animal models of autoimmune diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. Moreover, we include the main studies concerning dysbiosis in humans and a critical discussion of the existing data on the use of probiotics in these autoimmune diseases.
Topical treatment of all‐trans retinoic acid inhibits murine melanoma partly by promoting CD8+ T‐cell immunity
Authors: Yin Wei , Song Yan , Liu Qing , Wu Yunyun , He Rui
Published: May 2017

All‐trans retinoic acid (atRA), the main biologically active metabolite of vitamin A, has been implicated in immunoregulation and anti‐cancer. A recent finding that vitamin A could decrease the risk of melanoma in humans indicates the beneficial role of atRA in melanoma. However, it remains unknown whether topical application of atRA could inhibit melanoma growth by influencing tumour immunity. We demonstrate topical application of tretinoin ointment (atRA as the active ingredient) effectively inhibited B16F10 melanoma growth. This is accompanied by markedly enhanced CD8+ T‐cell responses, as evidenced by significantly increased proportions of effector CD8+ T cells expressing granzyme B, tumour necrosis factor‐α, or interferon‐γ, and Ki67+ proliferating CD8+ T cells in atRA‐treated tumours compared with vaseline controls. Furthermore, topical atRA treatment promoted the differentiation of effector CD8+ T cells in draining lymph nodes (DLN) of tumour‐bearing mice. Interestingly, atRA did not affect tumoral CD4+ T‐cell response, and even inhibited the differentiation of interferon‐γ‐expressing T helper type 1 cells in DLN. Importantly, we demonstrated that the tumour‐inhibitory effect of atRA was partly dependent on CD8+ T cells, as CD8+ T‐cell depletion restored tumour volumes in atRA‐treated mice, which, however, was still significantly smaller than those in vaseline‐treated mice. Finally, we demonstrated that atRA up‐regulated MHCI expression in B16F10 cells, and DLN cells from tumour‐bearing mice had a significantly higher killing rate when culturing with atRA‐treated B16F10 cells. Hence, our study demonstrates that topical atRA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD8+ T cells.
A quantitative systematic review of the effects of training interventions on enhancing the competence of nursing staff in managing challenging patient behaviour
Authors: Tölli Sirpa , Partanen Pirjo , Kontio Raija , Häggman‐Laitila Arja
Published: May 2017

Aims

This systematic quantitative review identifies and summarizes the current knowledge and effects of training interventions for managing patients' challenging behaviour.

Background

Challenging behaviour is an acknowledged worldwide healthcare problem and its management can have a huge impact on quality of care. Evidence‐based training interventions that focus on managing challenging behaviour are needed, but few tools for the systematic evaluation of these interventions are currently offered.

Design

A quantitative systematic review following the 2008 Centre for Reviews and Dissemination guidelines.

Data Sources

CINAHL, Scopus, PsycInfo, PubMed and Cochrane were searched using the same terms for papers published in English from 2005–2015.

Review Methods

Studies were assessed for quality and risk of bias, according to the Cochrane Effective Practice and Organisation of Care Group criteria. A narrative summary was conducted.

Results

We included 17 studies and evaluated 16 training interventions. Interventions were classified into four key themes: disengagements, communication, controlling behavioural symptoms and restrictive measures. Our review showed that interventions were more likely to decrease violent incident rates and increase staff confidence than change staff attitudes or increase knowledge. The elements of competence used to manage challenging behaviour were measured unilaterally. The evidence provided by studies was largely weak.

Conclusion

The variety of measurements used in the studies made comparing the effectiveness of the training interventions difficult. An individual's competence to manage challenging behaviour needs to be defined and a comprehensive scale for evaluating competence is also needed. Patient safety should be included in future evaluations.
Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature
Authors: Dias Christel , Giordano Mara , Frechette Rosalie , Bellone Simonetta , Polychronakos Constantin , Legault Laurent , Deal Cheri L , Goodyer Cynthia Gates
Published: May 2017

GH plays an essential role in the growing child by binding to the growth hormone receptor (GHR) on target cells and regulating multiple growth promoting and metabolic effects. Mutations in the GHR gene coding regions result in GH insensitivity (dwarfism) due to a dysfunctional receptor protein. However, children with idiopathic short stature (ISS) show growth impairment without GH or GHR defects. We hypothesized that decreased expression of the GHR gene may be involved. To test this, we investigated whether common genetic variants (microsatellites, SNPs) in regulatory regions of the GHR gene region were associated with the ISS phenotype. Genotyping of a GT‐repeat microsatellite in the GHR 5′UTR in a Montreal ISS cohort (n = 37 ISS, n = 105 controls) revealed that the incidence of the long/short (L/S) genotype was 3.3× higher in ISS children than controls (P = 0.04, OR = 3.85). In an Italian replication cohort (n = 143 ISS, n = 282 controls), the medium/short (M/S) genotype was 1.9× more frequent in the male ISS than controls (P = 0.017, OR = 2.26). In both ISS cohorts, logistic regression analysis of 27 SNPs showed an association of ISS with rs4292454, while haplotype analysis revealed specific risk haplotypes in the 3′ haploblocks. In contrast, there were no differences in GT genotype frequencies in a cohort of short stature (SS) adults versus controls (CARTaGENE: n = 168 SS, n = 207 controls) and the risk haplotype in the SS cohort was located in the most 5′ haploblock. These data suggest that the variants identified are potentially genetic markers specifically associated with the ISS phenotype.
The EF‐1α promoter maintains high‐level transgene expression from episomal vectors in transfected CHO‐K1 cells
Authors: Wang Xiaoyin , Xu Zhongjie , Tian Zhengwei , Zhang Xi , Xu Danhua , Li Qin , Zhang Junhe , Wang Tianyun
Published: May 2017

In our previous study, we demonstrated that episomal vectors based on the characteristic sequence of matrix attachment regions (MARs) and containing the cytomegalovirus (CMV) promoter allow transgenes to be maintained episomally in Chinese hamster ovary (CHO) cells. However, the transgene expression was unstable and the number of copies was low. In this study, we focused on enhancers, various promoters and promoter variants that could improve the transgene expression stability, expression magnitude (level) and the copy number of a MAR‐based episomal vector in CHO‐K1 cells. In comparison with the CMV promoter, the eukaryotic translation elongation factor 1 α (EF‐1α, gene symbol EEF1A1) promoter increased the transfection efficiency, the transgene expression, the proportion of expression‐positive clones and the copy number of the episomal vector in long‐term culture. By contrast, no significant positive effects were observed with an enhancer, CMV promoter variants or CAG promoter in the episomal vector in long‐term culture. Moreover, the high‐expression clones harbouring the EF‐1α promoter tended to be more stable in long‐term culture, even in the absence of selection pressure. According to these findings, we concluded that the EF‐1α promoter is a potent regulatory sequence for episomal vectors because it maintains high transgene expression, transgene stability and copy number. These results provide valuable information on improvement of transgene stability and the copy number of episomal vectors.
Generation of carbamoyl phosphate synthetase 1 reporter cell lines for the assessment of ammonia metabolism
Authors: Wang Yi , Chang Le , Zhai Jiahui , Wu Qiao , Wang Donggen , Wang Yunfang
Published: May 2017

Both primary hepatocytes and stem cells‐derived hepatocyte‐like cells (HLCs) are major sources for bioartificial liver (BAL). Maintenance of hepatocellular functions and induction of functional maturity of HLCs are critical for BAL's support effect. It remains difficult to assess and improve detoxification functions inherent to hepatocytes, including ammonia clearance. Here, we aim to assess ammonia metabolism and identify ammonia detoxification enhancer by developing an imaging strategy. In hepatoma cell line HepG2, and immortalized hepatic cell line LO2, carbamoyl phosphate synthetase 1 (CPS1) gene, the first enzyme of ammonia‐eliminating urea cycle, was labelled with fluorescence protein via CRISPR/Cas9 system. With the reporter‐based screening approach, cellular detoxification enhancers were selected among a collection of 182 small molecules. In both CPS1 reporter cell lines, the fluorescence intensity is positively correlated with cellular CPS1 mRNA expression, ammonia elimination and secreted urea, and reflected ammonia detoxification in a dose‐dependent manner. Surprisingly, high‐level CPS1 reporter clones also reserved many other critical hepatocellular functions, for example albumin secretion and cytochrome 450 metabolic functions. Sodium phenylbutyrate and resveratrol were identified to enhance metabolism‐related gene expression and liver‐enriched transcription factors C/EBPα, HNF4α. In conclusion, the CPS1‐reporter system provides an economic and effective platform for assessment of cellular metabolic function and high‐throughput identification of chemical compounds that improve detoxification activities in hepatic lineage cells.
Psoriasis in patients with mycosis fungoides: a clinicopathological study of 25 patients
Authors: Nikolaou V. , Marinos L. , Moustou E. , Papadavid E. , Economidi A. , Christofidou E. , Gerochristou M. , Tasidou A. , Economaki E. , Stratigos A. , Antoniou C.
Published: May 2017

Background

It has been reported that patients with psoriasis are at increased risk for developing lymphoma including cutaneous T‐cell lymphomas (CTCL). However, the comorbidity and the histopathologic correlation of psoriasis and mycosis fungoides (MF) have been less studied.

Objective

The objective of this study was to investigate the relation between MF and psoriasis.

Methods

We retrospectively reviewed and re‐evaluated all MF cases diagnosed and followed in a 16‐year period who carried both MF and psoriasis diagnoses.

Results

Forty‐one of 321 MF patients was the rate of psoriasis’ comorbidity according to medical records. Twenty‐five patients (7.8%) finally met the inclusion criteria. The rest were excluded due to inadequate evidence. Twenty patients had psoriatic lesions at the time of MF diagnosis. In 23 patients, there was histological confirmation of both diseases. Six patients (24%) were diagnosed with folliculotropic MF, two were diagnosed with pustular psoriasis, and six patients were affected by palmoplantar and nail psoriasis. In four patients, there was a very short time interval between MF and psoriasis diagnosis. Fourteen patients with psoriasis had been previously treated with immunomodulatory regimens. Interestingly, in eight patients, typical histological findings of both diseases were detected in the same biopsy specimen.

Conclusion

Our results support the opinion that the association between psoriasis and MF does exist. It is most possibly related to the chronic lymphocyte stimulation that occurs during psoriasis that eventually leads to a dominant clone and the evolution to CTCL. Our study suggests that apart from cases of early MF, which are being indeed misdiagnosed as psoriasis, there is another group of patients, where psoriasis truly coexists with – or even progresses to – MF.
Examining the role of the physician as a source of variation: Are physician‐related variations necessarily unwarranted?
Authors: Mercuri Mathew , Gafni Amiram
Published: May 2017

Rationale, Aims, and Objectives

The physician is often implicated as an important cause of observed variations in health care service use. However, it is not clear if physician‐related variation is problematic for patient care. This paper illustrates that observed physician‐related variation is not necessarily unwarranted.

Methods

This is a narrative review.

Results

Many studies have attributed observed variations to the physician, but little attention is given towards discriminating between those variations that exist for good reasons and those that are unwarranted. Two arguments can be made for why physician‐related variation is unwarranted. The first posits that physician‐related factors should not play a role in management of care decisions because such decisions should be driven by science (which is imagined to be definitive). The second considers the possibility of supplier‐induced demand as a factor driving observed variations. We show that neither argument is sufficient to rule out that physician‐related variations may be warranted. Furthermore, the claim that such variations are necessarily problematic for patients has yet to be substantiated empirically.

Conclusions

It is not enough to simply show that physician‐related variation can exist—one must also show where it is unwarranted and what is the magnitude of unwarranted variations. Failure to show this can have significant implications on how we interpret and respond to observed variations. Improved measurement of the sources of variation, especially with respect to patient preferences and context, may help us start to disentangle physician‐related variation that is desirable from that which is unwarranted.
Influence of high pressure homogenization with and without lecithin on particle size and physicochemical properties of whey protein‐based emulsions
Authors: Yan Bing , Park Sung Hee , Balasubramaniam V. M.
Published: May 2017

This study evaluated the quality attributes of high pressure homogenized whey protein emulsions with and without lecithin. Samples were prepared by mixing whey protein concentrate (10%), soybean oil (0 or 5%) and soy lecithin (0 or 5%). The premixtures were processed by a laboratory scale high pressure homogenizer at various pressures (25, 50, 75, and 100 MPa) at an initial temperature of 21 °C. The samples were evaluated for particle size, electrical conductivity, color, °Brix, and pH. Increasing homogenization pressures significantly decreased particle sizes of all samples. After 25 MPa treatment, emulsions with lecithin had smaller particle sizes than those made without lecithin. However, lecithin did not further reduce particle size for emulsion samples treated at ≥50 MPa. Electrical conductivity of samples increased with increasing homogenization pressures. Homogenization increased the lightness (L*) while reduced redness (a*) and yellowness (b*) of emulsions. The °Brix of emulsions increased after homogenization, but no change in pH was observed.

Practical applications

Consumer interest in clean label products prompted the food industry to investigate various processing methods such as high pressure homogenization to reduce additive use. The results of this study demonstrated the potential of applying high pressure homogenization in preparing whey protein‐based food products, with less use of lecithin.
Beyond the Individual: The Interdependence of Advance Directive Completion by Older Married Adults
Authors: Koss Catheryn S.
Published: May 2017

Objectives

To determine how individual and spousal demographic and health factors are associated with advance directive (AD) completion by married older adults.

Design

Dyadic structural equation modeling using the Actor‐Partner Interdependence Model.

Setting

The 2004 to 2012 waves of the Health and Retirement Study.

Participants

Community‐dwelling heterosexual married couples aged 65 and older (N = 2,243).

Measurements

Structural equation modeling with a probit link function was used to estimate associations between men's and women's age, education, health status, prior hospitalization or outpatient surgery in the past 10 years, regular health care provider, and household net assets and their own and their spouses’ probabilities of having an AD.

Results

Individual and spousal ages were each positively associated with AD completion for men and women. Those with higher education were more likely to possess ADs. Women's probabilities of having ADs were also positively associated with husbands’ education. Men whose wives’ were in poor health were less likely to have ADs. Men who were hospitalized or underwent outpatient surgery were more likely to have ADs, as were their wives. Women who had regular sources of health care were more likely to have completed ADs.

Conclusion

AD completion by older married adults is associated with both individual and spousal factors. How spouses influence one another's advance care planning differs by gender. Future research should account for the dyadic nature of advance care planning, as should public education efforts and interventions promoting AD completion.
A novel method to analyse in vivo the physiological state and cell viability of phototrophic microorganisms by confocal laser scanning microscopy using a dual laser
Authors: MILLACH LAIA , OBIOL ALEIX , SOLÉ ANTONIO , ESTEVE ISABEL
Published: May 2017

Phototrophic microorganisms are very abundant in extreme environments, where are subjected to frequent and strong changes in environmental parameters. Nevertheless, little is known about the physiological effects of these changing environmental conditions on viability of these microorganisms, which are difficult to grow in solid media and have the tendency to form aggregates. For that reason, it is essential to develop methodologies that provide data in short time consuming, in vivo and with minimal manipulating the samples, in response to distinct stress conditions.

In this paper, we present a novel method using Confocal Laser Scanning Microscopy and a Dual Laser (CLSM‐DL) for determining the cell viability of phototrophic microorganisms without the need of either staining or additional use of image treating software. In order to differentiate viable and nonviable Scenedesmus sp. DE2009 cells, a sequential scan in two different channels was carried out from each same xyz optical section. On the one hand, photosynthetic pigments fluorescence signal (living cells) was recorded at the red channel (625‐ to 785‐nm fluorescence emission) exciting the samples with a 561‐nm laser diode, and an acousto‐optic tunable filter (AOTF) of 20%. On the other hand, nonphotosynthetic autofluorescence signal (dead cells) was recorded at the green channel (500‐ to 585‐nm fluorescence emission) using a 405‐nm UV laser, an AOTF of 15%. Both types of fluorescence signatures were captured with a hybrid detector.

The validation of the CLSM‐DL method was performed with SYTOX green fluorochrome and electron microscopic techniques, and it was also applied for studying the response of distinct light intensities, salinity doses and exposure times on a consortium of Scenedesmus sp. DE2009.
The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule
Authors: Brucker Mary C. , King Tekoa L.
Published: May 2017

As of 2015, the US Food and Drug Administration (FDA) discontinued the pregnancy risk categories (ABCDX) that had been used to denote the putative safety of drugs for use among pregnant women. The ABCDX system has been replaced by the FDA Pregnancy and Lactation Labeling Rule (PLLR) that requires narrative text to describe risk information, clinical considerations, and background data for the drug. The new rule includes 3 overarching categories: 1) pregnancy, which includes labor and birth; 2) lactation; and 3) females and males of reproductive potential. This article reviews the key components of the PLLR and clinical implications, and provides resources for clinicians who prescribe drugs for women of reproductive age.
A rare complication of topical atropine for treatment of eccrine hidrocystoma: Pharmacological fixed dilated pupils
Authors: Zandi Alireza , Abtahi‐Naeini Bahareh , Pourazizi Mohsen
Published: May 2017

Multiple eccrine hidrocystoma (EH) has been treated with topical atropine with variable results. However, in rare cases, anticholinergic side effects have been seen after the use of the topical form of this drug. We presented a 50‐year‐old woman who developed recent onset of visual disturbance and photophobia from 2 weeks prior. The diagnosis of topical atropine‐induced bilateral mydriasis was made. We reported a recognized but often overlooked case of bilateral mydriasis caused by application of topical 1% atropine for treatment of multiple EH.