bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of oral vitamins and supplements in the management of atopic dermatitis: a systematic review
Authors: Reynolds Kelly A. , Juhasz Margit L. W. , Mesinkovska Natasha A.
Published: March 2019

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by disruption of epidermal barrier function and aberrant immune response to antigens. Current therapies focus on symptom management by restoring epidermal barrier function with emollients and reducing inflammation. Given the prevalence of “steroid phobia” and reported dissatisfaction with first‐line therapies, oral vitamins and supplements have been proposed as promising complementary and alternative therapies. The purpose of this systematic review is to evaluate the evidence for various oral vitamins and supplements for the treatment of AD. A literature search was performed in February 2018 in MEDLINE, EMBASE, and Cochrane databases. Included studies were clinical trials and meta‐analyses on the oral supplementation of vitamins and supplements for the treatment or prevention of AD. The search identified over 300 articles, of which 37 were included for review. Supplementation with vitamins E and D have the most robust evidence for AD symptom management. Probiotics may play a role in the prevention of infantile AD. Fatty acids such as docosahexaenoic acid, sea buckthorn oil, and hempseed oil also have preliminary evidence for use as supplements to decrease AD severity, but randomized controlled trials are needed. Vitamins and supplements may have a role in the management of AD, however, many of the studies reviewed are limited by small sample size. More studies are needed to better inform medical providers and patients about the role of these treatments in the management of AD.
HLA class I allele lineages and haplotype frequencies in Arabs of the United Arab Emirates
Authors: Kulski Jerzy K. , AlSafar Habiba S. , Mawart Aurelie , Henschel Andreas , Tay Guan K.
Published: March 2019

The high degree of polymorphism of the HLA system provides suitable genetic markers to study the diversity and migration of different world populations and is beneficial for forensic identification, anthropology, transplantation and disease associations. Although the United Arab Emirates (UAE) population of about nine million people is heterogeneous, information is limited for the HLA class I allele and haplotype frequencies of the Bedouin ethnic group. We performed low‐resolution PCR‐SSP genotyping of three HLA class I loci at HLA‐A, ‐B and ‐C for 95 unrelated healthy Bedouins from the cities of Al Ain and Abu Dhabi in the UAE. A total of 54 HLA allele lineages were detected; the most frequent low‐resolution allele lineages at each HLA locus were A*02 (0.268), B*51 (0.163) and C*07 (0.216). The inferred estimates for the two most frequent HLA‐A and HLA‐B haplotypes were HLA‐A*02 ~ HLA‐B*50 (0.070) and HLA‐A*02 ~ HLA‐B*51 (0.051), and the most frequent 3‐locus haplotype was HLA‐A*02 ~ HLA‐B*50 ~ HLA‐C*06 (0.068). The HLA allele lineage frequencies of the UAE Arabs were compared to those previously reported for 70 other world populations, and a strong genetic similarity was detected between the UAE Arabs and the Saudi Arabians from the west with evidence of a limited gene flow between the UAE Arabs and Pakistani across the Gulf from the east, and the UAE Arabs and Omani from the south of the Gulf Peninsula.
The effect of LILRB1 but not LILRA3 gene polymorphism in immunopathology of ankylosing spondylitis—A parallel to KIR genes
Authors: Majorczyk Edyta , Wiśniewski Andrzej , Zoń‐Giebel Aleksandra , Chlebicki Arkadiusz , Wiland Piotr , Kuśnierczyk Piotr
Published: March 2019

LILR and KIR receptors recognize HLA‐B27 and may influence immune response in ankylosing spondylitis (AS) development. Purpose of the study was to analyse LILRB1/LILRA3 polymorphisms in AS. We observed a possible protective effect of the T allele of LILRB1 rs1061680:T>C and no association with insertion/deletion polymorphisms of LILRA3 with AS.
Nation, Migration, Identity: Learning from the Cross‐Strait Context
Authors: Momesso Lara , Lee Chun‐yi
Published: March 2019

It has been argued that globalization, with its flexible landscapes of production, consumption and mobility, has favoured the emergence of new forms of belonging that are not necessarily built on such principles of the nation state. In this article, we argue that this process is more likely to happen when movements occur between states that are not in conflictual relations with each other. When the relations between two nations are shaped by conflicts, for instance due to disputes about sovereignty over a territory, nationalism may remain a crucial factor shaping the identification and belonging of those who move between the two territories. In this article, by looking at the case of migrants moving between China and Taiwan, we will shed light on how the issue of “unresolved sovereignty” may eventually lead these actors to reinforce nationalist ideals and identities in their daily narratives, instead of favouring the generation of hybrid identities.
What is new in lipid‐lowering therapies in diabetes?
Authors: Cheung Yee‐Ming , O’Brien Richard , Ekinci Elif I.
Published: March 2019

Diabetes can lead to a myriad of microvascular and macrovascular complications – with the leading cause of mortality in diabetes being cardiovascular disease. Low‐density lipoprotein cholesterol, along with non‐high‐density lipoprotein cholesterol and triglycerides are proven, modifiable risk factors for cardiovascular disease. This article will focus on lipid‐lowering agents in individuals with diabetes. It will summarise relevant changes in the latest guidelines for dyslipidaemia and will also review the mechanisms of action of lipid‐lowering agents along with the latest cardiovascular outcomes data specific to individuals with diabetes. Older agents such as statins, ezetimibe, fibrates and nicotinic acid will be reviewed with a focus on new diabetes‐specific evidence. Similarly, a relatively novel agent proprotein‐convertase subtilisin‐kexin type 9 will be reviewed and details around the Pharmaceutical Benefits Scheme criteria governing its usage in Australia will be reported. Finally, this review will touch on agents still on the horizon such as icosapent ethyl, high‐density lipoprotein mimetics, bempedoic acid, omega‐3 free fatty acids, bromodomain and extra‐terminal protein inhibitors and inclisiran – a long‐acting ribonucleic acid interference agent. In the appropriately selected population of individuals with diabetes, these agents can assist to improve further lipid profile and reduce cardiovascular events.
Association between bruxism and temporomandibular disorders in children: A systematic review and meta‐analysis
Authors: de Oliveira Reis Larissa , Ribeiro Rosangela Almeida , Martins Carolina Castro , Devito Karina Lopes
Published: March 2019

Background

Bruxism in children and its relation to the development of temporomandibular disorders (TMD) has not been clearly determined yet.

Aim

The objective of this systematic review was to evaluate the possible association between bruxism and TMD in children.

Design

Seven databases were searched, and 497 articles were assessed. Methodological quality was assessed through Newcastle‐Ottawa Scale. The meta‐analysis was performed with the articles in which extraction of data was possible and the summary effect measure through odds ratio (OR) and respective 95% confidence intervals (CIs). Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence.

Results

Ten cross‐sectional studies were included in the systematic review. Of these, 8 showed a statistically significant association between bruxism and TMD. Seven studies however presented a high risk of bias. The meta‐analysis was performed with 3 articles and obtained an OR of 2.97 (95% CI ranging from 1.72‐5.15), indicating that children with bruxism are 2.97 times more likely to present TMD, with very low level of certainty defined by GRADE.

Conclusions

Although the studies showed high risk of bias, the qualitative analysis of individual studies showed that the children with bruxism have greater chance of developing TMD.
Effect of a relaxation training exercise on behaviour, anxiety, and pain during buccal infiltration anaesthesia in children: Randomized clinical trial
Authors: Sridhar Sowmya , Suprabha Baranya Shrikrishna , Shenoy Ramya , Shwetha Kunnumal Thekkeveetil , Rao Arathi
Published: March 2019

Background

Cognitive behavioural techniques can decrease procedural pain and anxiety in children. Bubble breath exercise, a play therapy technique, may be used as a relaxation strategy to manage anxiety and pain. The objective of the study was to evaluate the effect of bubble breath exercise on dental anxiety, dental behaviour, and pain intensity during buccal infiltration of local anaesthetic in children.

Study Design

This randomized controlled trial involved 66 children aged 7‐11 years, randomly allocated to two groups: Group 1 (control) and Group 2 (intervention group). Group 2 was trained in bubble breath exercise. The reaction during buccal infiltration anaesthesia was recorded in terms of behaviour (Frankl's behaviour rating scale), anxiety (Facial Image Scale and pulse rate), and pain perception (Wong‐Baker FACES pain rating scale and the Faces, Leg, Activity, Cry, and Consolability scale).

Results

The bubble breath exercise significantly reduced the pain perceived, as measured by both the Wong‐Baker FACES pain rating scale (P < 0.001) and the FLACC scale (P < 0.001). There was no statistically significant difference in dental anxiety and behaviour among the groups.

Conclusion

Use of bubble breath exercise may be beneficial in decreasing the pain perceived during maxillary buccal infiltration anaesthesia in 7‐ to 11‐year‐old children.
An ERNSGA‐III algorithm for the production and distribution planning problem in the multiagent supply chain
Authors: Gharaei Ali , Jolai Fariborz
Published: March 2019

Nowadays, new issues have been emerged in industry by increasing the supply chain boundaries, especially when some supply chain members seek their own interests. In the literature, this case is referred to as a multiagent problem in which each agent has his/her own set of jobs and objectives. Here, an integrated production scheduling and distribution problem in a multisite supply chain is investigated from the three‐agent perspective of the manufacturer, distributor, and customer. Due to the complexity of the problem, a novel evolutionary‐based reference point determination of the third version of the non‐dominated sorting genetic algorithm (ERNSGA‐III) is proposed. In this algorithm, some modifications to the classic version of NSGA‐III have been made and a novel reference point determination method based on Bees algorithm is used in the selection operation. Some statistical tests are performed to compare the proposed algorithm with three other algorithms in the literature. The results show that the proposed algorithm is more effective than other algorithms.
Optimization of departure runway scheduling incorporating arrival crossings
Authors: Ma Ji , Sbihi Mohammed , Delahaye Daniel
Published: March 2019

The runway is a key airport resource and an efficient runway operation is critical to enhance the airport efficiency and to reduce delays. This paper addresses the problem of scheduling aircraft departures incorporating arrival crossings. Constraints for wake turbulence separations, flight time window restrictions, and holding queue capacity at runway threshold are explicitly considered. We present two integer linear programming models and a simulated annealing (SA) algorithm. Comparison tests are conducted for the south side of Paris Charles De Gaulle Airport and show that the three proposed methods can significantly improve the solutions based on the simple first‐come‐first‐served rule. Moreover, SA has sufficiently small computation time for real‐time deployment.
The sporadic nature of Legionella pneumophila, Legionella pneumophila Sg1 and Mycobacterium avium occurrence within residences and office buildings across 36 states in the United States
Authors: Donohue M.J. , King D. , Pfaller S. , Mistry J.H.
Published: March 2019

Aim

Premise plumbing may disseminate the bacteria Legionella pneumophila and Mycobacterium avium, the causative agents for legionellosis and pulmonary nontuberculous mycobacterium disease respectively.

Methods and Results

Using quantitative PCR, the occurrence and persistence of L. pneumophila, L. pneumophila serogroup (Sg)1 and M. avium were evaluated in drinking water samples from 108 cold water taps (residences: n = 43) and (office buildings: n = 65). Mycobacterium avium, L. pneumophila and L. pneumophila Sg1 were detected 45, 41 and 25% of all structures respectively. Two occurrence patterns were evaluated: sporadic (a single detection from the three samplings) and persistent (detections in two or more of the three samples).

Conclusions

The micro-organism's occurrence was largely sporadic. Office buildings were prone to microbial persistence independent of building age and square footage. Microbial persistence at residences was observed in those older than 40 years for L. pneumophila and was rarely observed for M. avium. The microbial occurrence was evenly distributed between structure types but there were differences in density and persistence.

Significance of and Impact of the Study

The study is important because residences are often suspected to be the source when a case of disease is reported. These data demonstrate that this may not be the case for a sporadic incidence.
Extra‐pair offspring are less heterozygous than within‐pair offspring in American redstarts Setophaga ruticilla
Authors: Hajdasz Adrianne , McKellar Ann E. , Ratcliffe Laurene M. , Boag Peter T. , Marra Peter P. , Reudink Matthew W.
Published: March 2019

The vast majority of bird species are socially monogamous; however, extra‐pair paternity is nearly ubiquitous and a number of theories have been proposed to explain the prevalence of this mixed mating strategy. Here, we test the genetic compatibility hypothesis – the idea that females seek extra‐pair copulations with males whose genes are more compatible with her own. For this study, we examined eight years of paternity data (2004–2011) from a Nearctic‐Neotropical migratory bird, the American redstart Setophaga ruticilla, breeding in southeastern Ontario, Canada. We predicted that females paired with genetically similar males (higher relatedness) would be more likely to produce extra‐pair offspring and that extra‐pair offspring would have higher levels of heterozygosity than within‐pair offspring. Alternatively, because this population experiences high levels of immigration, females may produce extra‐pair offspring with more genetically similar males because of the potential for outbreeding depression. Using five highly variable microsatellite markers, we examined patterns of relatedness among social pairs as well as measures of offspring heterozygosity. In contrast to our predictions, we found no difference in relatedness between social pairs where the females produced extra‐pair offspring and social pairs where the females produced only within‐pair offspring. However, extra‐pair offspring were significantly less heterozygous than within‐pair offspring. Together, these findings suggest that females a) are not engaging in extra‐pair fertilizations based on relatedness to their social mate and b) appear to be mating with extra‐pair males that are more genetically similar to themselves. We suggest there may be benefits for females to mate with genetically similar extra‐pair males in highly outbred populations with high rates of immigration, such as for maintaining co‐adapted gene complexes or genes coding for local adaptations.
Reticulate evolution in nuclear Middle America causes discordance in the phylogeny of palm‐pitvipers (Viperidae: Bothriechis)
Authors: Mason Andrew J. , Grazziotin Felipe G. , Zaher Hussam , Lemmon Alan R. , Moriarty Lemmon Emily , Parkinson Christopher L.
Published: March 2019

Aim

A number of processes can lead to weak or conflicting phylogenetic signals, especially in geographically dynamic regions where unstable landscapes and climates promote complex evolutionary histories. The Middle American pitviper genus Bothriechis has a complex biogeographic distribution and previous phylogenetic analyses have recovered conflicting topologies based on the data type used. Here, we tested whether historic conflicts in the phylogeny were the result of reticulate evolution and whether the inferred biogeographic history of the group would enable contact among reticulate lineages.

Location

Middle America.

Taxon

Palm‐pitvipers (genus Bothriechis).

Methods

We generated a phylogenomic dataset using an anchored phylogenomics approach and inferred a genomics‐based species tree and mitochondrial tree to assess incongruence among datasets. We then generated a dated phylogeny and conducted ancestral area reconstruction to examine the biogeographic history surrounding the diversification of these species. We additionally tested whether the discordance among trees is better explained by lineage sorting or reticulate evolution by testing models of reticulate evolution inferred through multiple methods.

Results

We found strong support for discordance in the phylogeny of Bothriechis and corresponding evidence for reticulate evolution among lineages with incongruent placement. Ancestral area reconstruction placed these taxa in adjacent regions during the time period when reticulation was projected to take place and suggested a biogeographic history heavily influenced by vicariant processes.

Main conclusions

Reticulation among geographically proximate lineages has driven apparent genomic discordance in Bothriechis and is responsible for historical incongruence in the phylogeny. Inference of the order of events suggests that reticulation among nuclear Middle American taxa occurred during a time of geologic upheaval, promoting lineage divergence and secondary contact. Reticulate evolution and similar processes can have substantial impacts on the evolutionary trajectory of taxa and are important to explicitly test for in biogeographically complex regions.
PMEPA1 induces EMT via a non‐canonical TGF‐β signalling in colorectal cancer
Authors: Zhang Lei , Wang Xue , Lai Chong , Zhang Honghe , Lai Maode
Published: March 2019

Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression. Metastasis is the main factor leading to cancer progression and poor prognosis, and at the beginning of metastasis, epithelial‐to‐mesenchymal transition (EMT) is a crucial activation. However, the relationship between PMEPA1 and EMT in colorectal cancer metastasis is still poorly understood. In this study, we first testified that PMEPA1 expresses higher in tumour than normal tissue in Gene Expression Omnibus database, in the Cancer Genome Atlas (TCGA) as well as in the clinical data we collected. Moreover, the higher expression was associated with poor prognosis. We furthermore demonstrated PMEPA1 promotes colorectal cancer metastasis and EMT in vivo and in vitro. We found that PMEPA1 activates the bone morphogenetic proteins (BMP) signalling of TGF‐β signalling resulting in promoting EMT and accelerating the proliferation and metastasis of colorectal cancer.
Conditioned media from dental pulp stem cells improved diabetic polyneuropathy through anti‐inflammatory, neuroprotective and angiogenic actions: Cell‐free regenerative medicine for diabetic polyneuropathy
Authors: Makino Eriko , Nakamura Nobuhisa , Miyabe Megumi , Ito Mizuho , Kanada Saki , Hata Masaki , Saiki Tomokazu , Sango Kazunori , Kamiya Hideki , Nakamura Jiro , Miyazawa Ken , Goto Shigemi , Matsubara Tatsuaki , Naruse Keiko
Published: March 2019

Aims/Introduction

Dental pulp stem cells (DPSCs) can be easily obtained from teeth for general orthodontic reasons. We have previously reported the therapeutic effects of DPSC transplantation for diabetic polyneuropathy. As abundant secretomes from DPSCs are considered to play a central role in the improvement of diabetic polyneuropathy, we investigated whether direct injection of DPSC‐conditioned media (DPSC‐CM) into hindlimb skeletal muscles ameliorates diabetic polyneuropathy in diabetic rats.

Materials and Methods

DPSCs were isolated from the dental pulp of Sprague–Dawley rats. Eight weeks after the induction of diabetes, DPSC‐CM was injected into the unilateral hindlimb skeletal muscles in both normal and diabetic rats. The effects of DPSC‐CM on diabetic polyneuropathy were assessed 4 weeks after DPSC‐CM injection. To confirm the angiogenic effect of DPSC‐CM, the effect of DPSC‐CM on cultured human umbilical vascular endothelial cell proliferation was investigated.

Results

The administration of DPSC‐CM into the hindlimb skeletal muscles significantly ameliorated sciatic motor/sensory nerve conduction velocity, sciatic nerve blood flow and intraepidermal nerve fiber density in the footpads of diabetic rats. We also showed that DPSC‐CM injection significantly increased the capillary density of the skeletal muscles, and suppressed pro‐inflammatory reactions in the sciatic nerves of diabetic rats. Furthermore, an in vitro study showed that DPSC‐CM significantly increased the proliferation of umbilical vascular endothelial cells.

Conclusions

We showed that DPSC‐CM injection into hindlimb skeletal muscles has a therapeutic effect on diabetic polyneuropathy through neuroprotective, angiogenic and anti‐inflammatory actions. DPSC‐CM could be a novel cell‐free regenerative medicine treatment for diabetic polyneuropathy.
Alopecia areata: a long‐term follow‐up study of 104 patients
Authors: Lyakhovitsky A. , Aronovich A. , Gilboa S. , Baum S. , Barzilai A.
Published: March 2019

Background

Alopecia areata (AA) is a common autoimmune disease that considerably affects the quality of life. Although several studies have investigated the epidemiology, clinical characteristics and treatment of AA, limited recent data are available regarding its long‐term course.

Objectives

To evaluate the long‐term course of AA in different age groups.

Methods

A retrospective evaluation of patients who were newly diagnosed with AA from 2008 to 2011 and had at least 7 years of follow‐up. Data regarding the initial episode, treatment given, disease‐free interval and relapses were analysed.

Results

A total of 104 cases were analysed: 31 childhood‐onset, 63 adult‐onset and 10 late‐onset. At first episode, 88.5% of patients had mild, 3.8% moderate and 7.7% severe AA. Full or significant re‐growth was observed in 74%, 94% and 100% of childhood‐onset, adult‐onset and late‐onset AA patients, respectively. There was no re‐growth in 13%, 3% and 0% of childhood‐onset, adult‐onset and late‐onset patients, respectively. The duration of the initial episode and the disease‐free interval negatively correlated with age. Systemic steroids were the most effective treatment for the primary episode. The frequency of relapses was high overall (52%, 44% and 30% in childhood‐onset, adult‐onset and late‐onset, respectively), but significantly declined over time with a majority (79%) occurring within the first 4 years. The disease‐free interval and relapse rate were not correlated with gender, disease severity at onset or treatment given.

Conclusions

The prevalence of severe disease, duration of an initial episode and the rate of relapses decreased with an older age at onset. In addition, the outcome and the disease‐free interval improved with age at onset. The frequency of relapses declined over time and most appear early on. The current treatment modalities do not seem to influence the long‐term outcome.
Influence of Multimorbidity on Burden and Appropriateness of Implantable Cardioverter‐Defibrillator Therapies
Authors: Hajduk Alexandra M. , Gurwitz Jerry H. , Tabada Grace , Masoudi Frederick A. , Magid David J. , Greenlee Robert T. , Sung Sue Hee , Cassidy‐Bushrow Andrea E. , Liu Taylor I. , Reynolds Kristi , Smith David H. , Fiocchi Frances , Goldberg Robert , Gill Thomas M. , Gupta Nigel , Peterson Pamela N. , Schuger Claudio , Vidaillet Humberto , Hammill Stephen C. , Allore Heather , Go Alan S. ,   for the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators
Published: March 2019

OBJECTIVE

To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies.

DESIGN

Retrospective cohort study.

SETTING

Seven US healthcare delivery systems.

PARTICIPANTS

Adults with left ventricular systolic dysfunction receiving an implantable cardioverter‐defibrillator (ICD) for primary prevention.

MEASUREMENTS

Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0‐3, 4‐5, 6‐7 and 8‐16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy.

RESULTS

Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4‐8), with 98% having at least two comorbidities. During a mean 2.2 years of follow‐up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14‐3.31] for 4‐5 comorbidities; HR = 2.25 [95% CI = 1.25‐4.05] for 6‐7 comorbidities; and HR = 2.91 [95% CI = 1.54‐5.50] for 8‐16 comorbidities). Participants with 8‐16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43‐3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67‐6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07‐2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies.

CONCLUSIONS

In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation.
Traumatic Experiences and the Midwifery Profession: A Cross‐Sectional Study Among Dutch Midwives
Authors: Kerkman Tessa , Dijksman Lea M. , Baas Melanie A.M. , Evers Ruth , van Pampus Maria G. , Stramrood Claire A.I.
Published: March 2019

Introduction

Traumatic events that occur in a clinical setting can have long‐lasting adverse effects on persons who are affected, including health care providers. This study investigated the prevalence of work‐related traumatic events, posttraumatic stress disorder (PTSD), anxiety, and depression among Dutch midwives. Additionally, differences between midwives working in primary care (independently assisting births at home and in birthing centers) and midwives working in secondary or tertiary care (hospital setting) were examined. Finally, this study investigated the support midwives would like to receive after experiencing a work‐related adverse event.

Methods

A descriptive, cross‐sectional online survey of Dutch midwives was conducted. The respondents completed a questionnaire about demographic and work‐related events, as well as the Trauma Screening Questionnaire and the Hospital Anxiety and Depression Scale.

Results

The estimated response rate was 23%, with 691 questionnaires eligible for analysis. Thirteen percent of respondents reported having experienced at least one work‐related traumatic event. Among these, 17% screened positive for PTSD, revealing an estimated PTSD prevalence of 2% among Dutch midwives. Clinically relevant anxiety symptoms were reported by 14% of the respondents, significantly more often among midwives working in primary care (P = .014). Depressive symptoms were reported by 7% of the respondents. The desired strategies to cope with an adverse event were peer support by direct colleagues (79%), professional support from a coach or psychologist (30%), multidisciplinary peer support (28%), and support from midwives who are not direct coworkers (17%).

Discussion

Dutch midwives are at risk of experiencing work‐related stressful or traumatic events that might lead to PTSD, anxiety, or depression. Midwives working in primary care reported higher levels of anxiety compared with their colleagues working in a clinical setting (secondary or tertiary care). Most midwives preferred peer support with direct colleagues after an adverse event, and some could have profited from easier access to seeking professional help. It could be speculated that midwives would benefit from increased awareness about work‐related traumatic events as well as implementation of standardized guidelines regarding support after a traumatic event.
Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists
Authors: Bonaventura A. , Carbone S. , Dixon D. L. , Abbate A. , Montecucco F.
Published: March 2019

Patients with type 2 diabetes mellitus (T2D) present an increased risk for cardiovascular (CV) complications. In addition to improvement in glycaemic control, glucose‐lowering therapies, such as glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐dependent glucose cotransporter (SGLT)‐2 inhibitors, have been shown to significantly reduce CV events. In 2008, the US Food and Drug Administration mandated that all new glucose‐lowering drugs undergo CV outcomes trials (CVOTs) to determine their CV safety. These trials have largely demonstrated no major CV safety concerns. Most notably, the GLP‐1RAs and SGLT‐2 inhibitors have been found to be not only safe, but also cardioprotective compared to placebo. The SGLT‐2 inhibitors have opened a new perspective for clinicians treating patients with T2D and established CV disease in light of their ‘pleiotropic’ effects, specifically on heart failure, while GLP‐1RAs seem to present more favourable effects on atherosclerotic events. In this review, we discuss the role of GLP‐1RAs and SGLT‐2 inhibitors to reduce CV risk in T2D patients and suggest an individualized therapeutic approach in this population based on the presence of metabolic and CV comorbidities.
School Personnel's Bystander Action in Situations of Teen Relationship Abuse and Sexual Assault: Prevalence and Correlates
Authors: Edwards Katie M. , Sessarego Stephanie N. , Banyard Victoria L. , Rizzo Andrew J. , Mitchell Kimberly J.
Published: March 2019

BACKGROUND

Relationship abuse (RA) and sexual assault (SA) are major problems among high school students, and school personnel are an important part of preventing RA and SA among youth. Therefore, we examined the rates and correlates of bystander intentions among school personnel in situations of RA and SA.

METHODS

School personnel (N = 1150) from 25 high schools in New England completed surveys that assessed their RA and SA knowledge, perceptions of school climate specific to RA and SA, and RA and SA bystander efficacy and bystander intentions.

RESULTS

Across each type of bystander behavior measured, the vast majority of school personnel reported intentions to intervene. In the multilevel regression analyses, both proactive and reactive bystander intentions were related to higher levels of RA and SA bystander efficacy and perceptions of a more positive school climate and lower levels of RA and SA barriers to intervene.

CONCLUSIONS

These data support the utility of school‐based interventions that seek to improve school climate and teach school personnel skills that enhance bystander efficacy and reduce bystander barriers in student situations of RA and SA. Although they would need to be evaluated, such interventions could promote positive bystander action among school personnel and untimely contribute to reductions in RA and SA among high school youth.
Angiopoietin‐like 4 production upon treatment with hypoxia and L‐mimosine in periodontal fibroblasts
Authors: Janjić Klara , Schellner Alwina , Engenhart Alexander , Kernstock Kurt , Schädl Barbara , Moritz Andreas , Agis Hermann
Published: March 2019

Background and objective

A key factor in the modulation of angiogenesis as well as in bone resorption is angiopoietin‐like 4. However, the role of angiopoietin‐like 4 in periodontal tissue is unknown. Here, we hypothesized that hypoxia and the hypoxia mimetic agent L‐mimosine can induce the production of angiopoietin‐like 4 in periodontal fibroblasts.

Methods

Human periodontal ligament fibroblasts (PDLF) were cultured in monolayer and spheroid cultures. The cultures were incubated in the presence of hypoxia or L‐mimosine. Angiopoietin‐like 4 mRNA and protein levels were measured by qPCR and ELISA, respectively. Also, the impact of Lipopolysaccharides of E. coli and P. gingivalis, interleukin (IL)‐1β and tumor necrosis factor (TNF)α was evaluated. Furthermore, we tested dependency on hypoxia‐inducible factor (HIF)‐1 activity by Western blotting for HIF‐1 and inhibitor studies with echinomycin. Potential autocrine effects were assessed by exposure of PDLF to recombinant angiopoietin‐like 4 in full length, C‐terminal and N‐terminal fragments. The impact on viability, DNA synthesis, alkaline phosphatase, and matrix mineralization was evaluated.

Results

Both hypoxia and L‐mimosine elevated angiopoietin‐like 4 mRNA and protein levels in monolayer cultures of PDLF. HIF‐1 was elevated after both hypoxia and L‐mimosine treatment. LPS, IL‐1β, and TNFα did not modulate angiopoietin‐like 4 levels significantly. Addition of echinomycin in the cultures inhibited the production of angiopoietin‐like 4. In spheroid cultures of PDLF, the increase did not reach the level of significance at mRNA and protein levels. Angiopoietin‐like 4 in full length, C‐terminal, and N‐terminal fragments did not modulate viability, DNA synthesis, alkaline phosphatase, and matrix mineralization.

Conclusion

Overall, we found that hypoxia and the hypoxia mimetic agent L‐mimosine can stimulate angiopoietin‐like 4 production in monolayer cultures of PDLF. This increase depends on HIF‐1 activity. Future studies will reveal how the modulation of angiopoietin‐like 4 in the periodontium contributes to periodontal disease and regeneration.
A comparison of the rates of postoperative complications between dogs undergoing laparoscopic and open ovariectomy
Authors: Charlesworth T. M. , Sanchez F. T.
Published: March 2019

Objectives

To investigate whether dogs undergoing laparoscopic ovariectomy might have a lower overall and wound‐healing complication rate than those undergoing an open surgical approach.

Materials and Methods

A retrospective study of dogs that underwent laparascopic or open surgical ovariectomy between January 1, 2013 and January 1, 2018 by the same team of similarly experienced surgeons using standard practice anaesthetic, theatre and perioperative protocols. General complications were described and graded using the Clavien‐Dindo system. Complication rates were compared between the two groups of dogs. Wound complications were further subdivided using the U.S. Centers for Disease Control guidelines.

Results

According to the Clavien‐Dindo system, 46 of 106 (44%) dogs undergoing open ovariectomy developed a complication. Thirty dogs (28.3%) had wound healing complications, the majority of which were minor and self‐limiting. Superficial site infections occurred in 50 (5%) cases and deep surgical site infections in one dog (1%). Incisional herniation occurred in four (4%) cases. Thirty‐one (20%) of 154 dogs undergoing laparoscopic ovariectomy developed a complication. Seventeen (11%) developed wound healing complications, most of which were minor; five (3%) developed superficial surgical site infections and none had deep surgical site infections. Incisional herniation occurred in none of the laparoscopic cases.

Clinical Significance

The rates of overall and wound healing complications were lower for the laparascopic group than the open surgical group in this non‐randomised study. Laparoscopy might be considered preferable for ovariectomy in dogs but confirmation requires a randomised trial.
Sex allocation plasticity on a transcriptome scale: Socially sensitive gene expression in a simultaneous hermaphrodite
Authors: Ramm Steven A. , Lengerer Birgit , Arbore Roberto , Pjeta Robert , Wunderer Julia , Giannakara Athina , Berezikov Eugene , Ladurner Peter , Schärer Lukas
Published: March 2019

Phenotypic plasticity can enable organisms to produce optimal phenotypes in multiple environments. A crucial life history trait that is often highly plastic is sex allocation, which in simultaneous hermaphrodites describes the relative investment into the male versus female sex functions. Theory predicts—and morphological evidence supports—that greater investment into the male function is favoured with increasing group size, due to the increasing importance of sperm competition for male reproductive success. Here, we performed a genome‐wide gene expression assay to test for such sex allocation plasticity in a model simultaneous hermaphrodite, the free‐living flatworm Macrostomum lignano. Based on RNA‐Seq data from 16 biological replicates spanning four different group size treatments, we demonstrate that at least 10% of the >75,000 investigated transcripts in M. lignano are differentially expressed according to the social environment, rising to >30% of putative gonad‐specific transcripts (spermatogenesis and oogenesis candidates) and tail‐specific transcripts (seminal fluid candidates). This transcriptional response closely corresponds to the expected shift away from female and towards male reproductive investment with increasing sperm competition level. Using whole‐mount in situ hybridization, we then confirm that many plastic transcripts exhibit the expected organ‐specific expression, and RNA interference of selected testis‐ and ovary‐specific candidates establishes that these indeed function in gametogenesis pathways. We conclude that a large proportion of sex‐specific transcripts in M. lignano are differentially expressed according to the prevailing ecological conditions and that these are functionally relevant to key reproductive phenotypes. Our study thus begins to bridge organismal and molecular perspectives on sex allocation plasticity.
Higher glutathione demand may be necessary for assisting haemodialysis patients to cope with increased oxidative stress
Authors: Yeh En‐Ling , Chen Cheng‐Hsu , Huang Shih‐Chien , Huang Yi‐Chia
Published: March 2019

Aim

The removal of cysteine during a dialysis procedure may affect glutathione (GSH) concentration, allowing haemodialysis (HD) patients to become more susceptible to oxidative damage. This study was performed to determine whether the change of GSH/glutathione disulfide (GSSG) redox state and GSH redox potential were linked with the change of cysteine or oxidative stress in patients receiving HD treatment.

Methods

Sixty‐seven HD patients who had received regular HD treatment were recruited. Plasma GSH, GSSG, cysteine and malondialdehyde (MDA) were measured at both pre‐ and post‐HD.

Results

Plasma cysteine, GSH and GSSG levels significantly decreased after the completion of HD, compared to the levels at pre‐HD. Plasma MDA concentration, GSH/GSSG ratio and GSH redox potential remained constant during the dialysis session. Plasma GSH and GSSG were positively associated with plasma MDA at post‐HD, while GSH redox potential was negatively associated with plasma MDA at post‐HD. However, plasma GSH, GSSG, GSH/GSSG ratio and GSH redox potential were not associated with plasma cysteine at either pre‐ or post‐HD.

Conclusion

The GSH and GSSG levels were significantly utilized during a HD session, and their levels were significantly associated with increased oxidative stress. HD patients may require higher GSH demands to cope with increased oxidative stress during an HD session.
Clinical features and outcomes of kidney transplant recipients with focal segmental glomerulosclerosis recurrence
Authors: Mansur Juliana B , Sandes‐Freitas Tainá V , Kirsztajn Gianna M , Cristelli Marina P , Mata Gustavo F , de Paula Mayara I , Grenzi Patricia C , Martins Suelen B S , Felipe Claudia R , Tedesco‐Silva Hélio , Pestana José O M
Published: March 2019

Aim

Focal segmental glomerulosclerosis recurs in up to 30% and up to 80% of adult and pediatric kidney transplant recipients, respectively. There is no standard of care treatment. The purpose of this study was to evaluate clinical characteristics, treatments and outcomes of patients with focal segmental glomerulosclerosis recurrence (FSGSr).

Methods

This was a retrospective single‐center cohort study including FSGSr patients treated with plasmapheresis (PP) and combinations of high dose steroids, cyclosporine and rituximab.

Results

Among 61 patients included in this analysis the median time to diagnosis was 19 days. The incidence of first biopsy‐confirmed FSGSr was 18% reaching 52.4% with follow‐up biopsies. During PP treatment 54% of the patients developed infectious complications. PP was discontinued in 37% of patients due to treatment failure (no remission or graft loss) and in 26% due to an adverse event. All patients who discontinued PP due to adverse event did not show clinical response or lost the allograft. The incidence of acute rejection was 34.4%. The incidences of partial and complete remissions were 16.4% and 27.8%, respectively. Overall 6‐years patient and graft survivals were 90.7% and 64.5%, respectively.

Conclusion

This analysis confirms the low, variable and unpredictable rate of FSGSr remission, inconsistencies among available therapeutic options and its high rate of adverse events, and the negative impact on graft survival.
Allopolyploidy in the Wintergreen Group of tribe Gaultherieae (Ericaceae) inferred from low‐copy nuclear genes
Authors: Lu Lu , Fritsch Peter W. , Bush Catherine M. , Wang Hong , Kron Kathleen A. , Li De‐Zhu
Published: March 2019

DNA sequence data from the low‐copy nuclear geneswaxy(GBSSI) andleafywere compared with plastid and ITS sequence data from prior studies to reconstruct phylogenetic relationships in the Wintergreen Group of tribe Gaultherieae (Ericaceae). We conducted phylogenetic analysis with 102 species that includes representatives of all 15 major clades previously identified within the Wintergreen Group and that together span its circum‐Pacific distribution. Results yielded two distinct homeologous copies ofwaxyfor two of the clades, each in widely separated parts of the tree. It also yielded two copies ofleafyfor one of the clades; only one copy ofleafywas found for the other clade, but it was placed in the same major clade as itswaxycounterpart and well away from its placement in a prior plastid analysis. A combined four‐locus (waxy,leafy, ITS and plastid data) phylogenetic analysis of all available relevant data placed the copies of each of the clades in two distinct positions in the phylogeny with strong overall statistical support. In combination with evidence from morphology, reproductive biology and cytology, the results suggest that these clades arose through allopolyploid hybridization between lineages deep in the phylogeny but relatively close geographically. This finding confirms previous assumptions that hybridization has played an important role in the evolution of the Gaultherieae.
Leaf mechanical strength and photosynthetic capacity vary independently across 57 subtropical forest species with contrasting light requirements
Authors: He Pengcheng , Wright Ian J. , Zhu Shidan , Onoda Yusuke , Liu Hui , Li Ronghua , Liu Xiaorong , Hua Lei , Oyanoghafo Osazee O. , Ye Qing
Published: March 2019

Leaf mechanical strength and photosynthetic capacity are critical plant life‐history traits associated with tolerance and growth under various biotic and abiotic stresses. In principle, higher mechanical resistance achieved via higher relative allocation to cell walls should slow photosynthetic rates. However, interspecific relationships among these two leaf functions have not been reported.

We measured leaf traits of 57 dominant woody species in a subtropical evergreen forest in China, focusing especially on photosynthetic rates, mechanical properties, and leaf lifespan (LLS). These species were assigned to two ecological strategy groups: shade‐tolerant species and light‐demanding species.

On average, shade‐tolerant species had longer LLS, higher leaf mechanical strength but lower photosynthetic rates, and exhibited longer LLS for a given leaf mass per area (LMA) or mechanical strength than light‐demanding species. Depending on the traits and the basis of expression (per area or per mass), leaf mechanical resistance and photosynthetic capacity were either deemed unrelated, or only weakly negatively correlated.

We found only weak support for the proposed trade‐off between leaf biomechanics and photosynthesis among co‐occurring woody species. This suggests there is considerable flexibility in these properties, and the observed relationships may result more so from trait coordination than any physically or physiologically enforced trade‐off.
CITED2 mediates the cross‐talk between mechanical loading and IL‐4 to promote chondroprotection
Authors: He Zhiyong , Leong Daniel J. , Xu Lin , Hardin John A. , Majeska Robert J. , Schaffler Mitchell B. , Thi Mia M. , Yang Liu , Goldring Mary B. , Cobelli Neil J. , Sun Hui B.
Published: March 2019

Osteoarthritis (OA) pathogenesis is mediated largely through the actions of proteolytic enzymes such as matrix metalloproteinase (MMP) 13. The transcriptional regulator CITED2, which suppresses the expression of MMP13 in chondrocytes, is induced by interleukin (IL)‐4 in T cells and macrophages, and by moderate mechanical loading in chondrocytes. We tested the hypothesis that CITED2 mediates cross‐talk between IL‐4 signaling and mechanical loading‐induced pathways that result in chondroprotection, at least in part, by downregulating MMP13. IL‐4 induced CITED2 gene expression in human chondrocytes in a dose‐ and time‐dependent manner through JAK/STAT signaling. Mechanical loading combined with IL‐4 resulted in additive effects on inducing CITED2 expression and downregulating of MMP13 in human chondrocytes in vitro. In vivo, IL‐4 gene knockout (KO) mice exhibited reduced basal levels of CITED2 expression in chondrocytes. While moderate treadmill running induced CITED2 expression and reduced MMP13 expression in wild‐type mice, these effects were blunted (for CITED2) or abolished (for MMP13) in chondrocytes of IL‐4 gene KO mice. Moreover, intra‐articular injections of mouse recombinant IL‐4 combined with regular cage activity mitigated post‐traumatic OA to a greater degree compared to immobilized mice treated with IL‐4 alone. These data suggest that using moderate loading to enhance IL‐4 may be a potential therapeutic strategy for chondroprotection in OA.