bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective audit of patients referred for further treatment following Mohs surgery for non‐melanoma skin cancer
Authors: Wee Edmund , Goh Michelle S , Estall Vanessa , Tiong Albert , Webb Angela , Mitchell Catherine , Murray William , Tran Phillip , McCormack Christopher J , Henderson Michael , Hiscutt Emma L
Published: January 2018

Background/Objectives

To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

Methods

Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015.

Results

In total, 83 lesions in 82 patients were referred for further management; 52 (62%) were SCC and 80 (96%) were located in the head and neck. Reasons for referral included high‐risk disease for consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection (28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of the 69 referrals received from MMS surgeons included photos or an operative report and diagram.

There was discordance in pathology opinion in 11 (13%) of cases. Histopathology from MMS was reviewed in eight cases and there was discordance with the in‐hospital pathology opinion in six of these. In‐hospital re‐excision was performed in 19 cases and in five of these the pathology report on the paraffin‐sectioned re‐excised tissue was discordant with prior MMS assessment. Significantly, two cases were associated with a misinterpretation of lymphocytic infiltrate as residual disease in patients with chronic lymphocytic leukaemia (CLL).

Conclusion

This study highlights some of the challenges and limitations of MMS. Early referral for multidisciplinary management is recommended when MMS resection margins are inadequate or uncertain, especially for high‐risk SCC. We recommend that referrals be accompanied by histological material, as well as a detailed report with operative photos and diagrams. CLL can pose an intraoperative diagnostic challenge. Discrepancies in the interpretation of MMS slides present an opportunity for improvement, and our findings support the role of ongoing quality assurance programs.
Application of computer‐aided sperm analysis (CASA) for detecting sperm‐immobilizing antibody
Authors: Wakimoto Yu , Fukui Atsushi , Kojima Teruhito , Hasegawa Akiko , Shigeta Minoru , Shibahara Hiroaki
Published: January 2018

Problem

Since the 1970s, anti‐sperm antibodies have been studied as a pathogenic factor contributing to infertility. The complement‐dependent sperm‐immobilization test (SIT) and quantitative SIT have been used as effective tools for detecting anti‐sperm antibodies in clinical settings. These tests have been carried out traditionally by manually counting the number of motile sperm through eye estimation.

Method of study

In this study, we developed a novel method using computer‐aided sperm analysis. The results were compared with those obtained by the traditional method.

Results

The results were identical and 25 of 78 samples tested were positive and 53 samples were negative for sperm‐immobilizing (SI) antibodies based on both methods. For SI‐positive samples, the values of SI50 obtained using the two methods correlated closely with high co‐efficiency.

Conclusion

Using the novel method, manually counting the number of motile spermatozoa becomes unnecessary. The novel method presented here will increase the objectivity and convenience of using the SIT as a clinical indicator.
Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer
Authors: Einhorn L. , Hofstetter G. , Brandt S. , Hainisch E. K. , Fukuda I. , Kusano K. , Scheynius A. , Mittermann I. , Resch‐Marat Y. , Vrtala S. , Valenta R. , Marti E. , Rhyner C. , Crameri R. , Satoh R. , Teshima R. , Tanaka A. , Sato H. , Matsuda H. , Pali‐Schöll I. , Jensen‐Jarolim E.
Published: January 2018

Background

Companion animals are also affected by IgE‐mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles.

Methods

Custom‐designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic.

Results

Horses showed individual IgE‐binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S‐albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet.

Conclusion

In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen‐specific preventive and therapeutic concepts.
Intraoperative adverse events associated with extremely preterm cesarean deliveries
Authors: Bertholdt Charline , Menard Sophie , Delorme Pierre , Lamau Marie‐Charlotte , Goffinet François , Le Ray Camille
Published: January 2018

Introduction

At the same time as survival is increasing among premature babies born before 26 weeks of gestation, the rates of cesarean deliveries before 26 weeks is also rising. Our purpose was to compare the frequency of intraoperative adverse events during cesarean deliveries in two gestational age groups: 24–25 weeks and 26–27 weeks.

Material and methods

This single‐center retrospective cohort study included all women with cesarean deliveries performed before 28+0 weeks from 2007 through 2015. It compared the frequency of intraoperative adverse events between two groups: those at 24–25 weeks of gestation and at 26–27 weeks. Intraoperative adverse events were a classical incision, transplacental incision, difficulty in fetal extraction (explicitly mentioned in the surgical report), postpartum hemorrhage (≥500 mL of blood loss), and injury to internal organs. A composite outcome including at least one of these events enabled us to analyze the risk factors for intraoperative adverse events with univariate and multivariable analysis. Stratified analyses by the indication for the cesarean were performed.

Results

We compared 74 cesarean deliveries at 24–25 weeks of gestation and 214 at 26–27 weeks. Intraoperative adverse events occurred at higher rates in the 24–25‐week group (63.5 vs. 30.8%, p < 0.001). After adjustment for confounding factors, this group remained at significantly higher risk of intraoperative adverse events [adjusted odds ratio 5.04 (2.67–9.50)], even after stratification by indication for the cesarean.

Conclusion

These results should help obstetricians and women making decisions about cesarean deliveries at these extremely low gestational ages.
Low semen quality and experiences of masculinity and family building
Authors: Sylvest Randi , Fürbringer Jeanette K. , Pinborg Anja , Koert Emily , Bogstad Jeanette , Loessl Kristine , Praetorius Lisbeth , Schmidt Lone
Published: January 2018

Introduction

Infertility is a concern for men and women. There is limited knowledge on how male factor infertility affects the couple in fertility treatment. The aim of this study was to explore how severe male factor infertility affects men's sense of masculinity, the couple's relationship and intentions about family formation.

Material and methods

Semi‐structured qualitative interview study at the Fertility Clinic at Copenhagen University Hospital, Hvidovre, Denmark. Ten men with very poor semen quality initiating fertility treatment were interviewed between November 2014 and May 2015. Data were analyzed using qualitative content analysis.

Results

Three themes were identified: “Threatened masculinity”, “Being the strong one: impact on the couple” and “Consideration of family building options: a chapter not willing to start”. The men felt that they could not fulfill their role as a man. Some couples had conflicts and discussions because the women in general wanted to talk more about infertility than the men. The men focused on having a biological child. They wanted to focus on achieving biological parenthood and postpone consideration of other family building options such as adoption or the use of semen donation in order to become a parent.

Conclusions

The consequence of severe male factor infertility was a threatened sense of masculinity. Fertility specialists and nurses should recognize the impact of male infertility and create space to give their patients an opportunity to verbalize their concerns and questions related to male factor infertility and the different challenges that the couple faces during the fertility treatment.
The Legacy of Early Abuse and Neglect for Social and Academic Competence From Childhood to Adulthood
Authors: Raby K. Lee , Roisman Glenn I. , Labella Madelyn H. , Martin Jodi , Fraley R. Chris , Simpson Jeffry A.
Published: January 2018

This study used data from the Minnesota Longitudinal Study of Risk and Adaptation (N = 267) to investigate whether abuse and neglect experiences during the first 5 years of life have fading or enduring consequences for social and academic competence over the next 3 decades of life. Experiencing early abuse and neglect was consistently associated with more interpersonal problems and lower academic achievement from childhood through adulthood (32–34 years). The predictive significance of early abuse and neglect was not attributable to the stability of developmental competence over time, nor to abuse and neglect occurring later in childhood. Early abuse and neglect had enduring associations with social (but not academic) competence after controlling for potential demographic confounds and early sensitive caregiving.
Delayed initial radioiodine therapy related to incomplete response in low‐ to intermediate‐risk differentiated thyroid cancer
Authors: Li Hui , Zhang Ying‐qiang , Wang Chen , Zhang Xin , Li Xin , Lin Yan‐song
Published: January 2018

Objective

Whether the initiating time of radioiodine (RAI) therapy will affect the clinical outcome in differentiated thyroid cancer (DTC) remains controversial. The objective of this study was to evaluate the impact of RAI therapy initiating time on response to initial therapy in low‐ to intermediate‐risk DTC.

Methods

A total of 235 consecutive patients with low‐ to intermediate‐risk DTC were retrospectively reviewed. According to the time interval between thyroidectomy and RAI therapy, patients were divided into Group 1 (interval < 3 months, n = 187) and Group 2 (interval ≥ 3 months, n = 48). Response to RAI therapy was evaluated as excellent, indeterminate, biochemical incomplete or structural incomplete response (ER, IDR, BIR or SIR) with a median follow‐up of 780 days. The univariate and multivariate analyses were further conducted to identify factors associated with incomplete response (IR, including BIR and SIR).

Results

Response to initial therapy was significantly different between 2 groups (P < .05), after excluding the impact of other risk factors (age, gender, histological type, status of T and N, RAI dose, thyrotropin, stimulated thyroglobulin and follow‐up time). A significantly higher IR rate (18.8% vs 4.3%, P = .001) and a lower ER proportion (62.5% vs 78.1%, P = .027) were observed in Group 2. By univariate analysis, both T status and N status, stimulated thyroglobulin and time interval were significant risk factors for IR (P < .05). Multivariate analysis demonstrated that the time interval was an independent risk factor for IR (P = .008).

Conclusions

Delayed initial RAI therapy (≥3 months after thyroidectomy) related to incomplete response in low‐ to intermediate‐risk DTC.
Incidence and predictors of sudden cardiac death after heart transplantation: A systematic review and meta‐analysis
Authors: Alba Ana C. , Foroutan Farid , Ng Fat Hing Nicholas Kwet Vong , Fan Chun‐Po S. , Manlhiot Cedric , Ross Heather J.
Published: January 2018

Purpose

Sudden cardiac death (SCD) is an important post‐transplant problem being responsible for ~10% of deaths. We conducted a systematic review and meta‐analysis to evaluate incidence and predictors of post‐heart transplant SCD and the use of implantable cardiac defibrillator (ICD).

Methods

Citations were identified in electronic databases and references of included studies. Observational studies on adults reporting on incidence and predictors of post‐transplant SCD and ICD use were selected. We meta‐analyzed SCD in person‐years using random effects models. We qualitatively summarized predictors.

Results

This study includes 55 studies encompassing 47 901 recipients. The pooled incidence rate of SCD was 1.30 per 100 person‐years (95% CI: 1.08‐1.52). Cardiac allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100 patient‐years, 95% CI: 1.46‐3.34). Independent predictors of SCD identified by two moderate‐quality studies were older donor age, younger recipient age, non‐Caucasian race, reduced left ventricular ejection fraction, rejection, infection, and cancer. Authors rarely reported on ICD use.

Conclusion

This meta‐analysis found that post‐transplant SCD risk in heart transplant recipients is higher than that in the general population. CAV was associated with increased SCD risk. Observational studies reporting on absolute risk of SCD are needed to better identify populations at a clinically significant increased risk.
A Preclinical Population Pharmacokinetic Model for Anti‐CD20/CD3 T‐Cell‐Dependent Bispecific Antibodies
Authors: Ferl Gregory Z. , Reyes Arthur , Sun Liping L. , Cheu Melissa , Oldendorp Amy , Ramanujan Saroja , Stefanich Eric G.
Published: January 2018

CD20 is a cell‐surface receptor expressed by healthy and neoplastic B cells and is a well‐established target for biologics used to treat B‐cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti‐CD20/CD3 T‐cell‐dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time‐varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed‐effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time‐varying, linear clearance term (t½ = 1.6 h); and iii) a slowly decaying time‐varying, nonlinear clearance term (t½ = 4.8 days). The two time‐varying drug elimination terms approximately track with time scales of B‐cell depletion and T‐cell migration/expansion within the central blood compartment. The mixed‐effects NHP model was scaled to human and prospective clinical simulations were generated.
Late Cretaceous marine arthropods relied on terrestrial organic matter as a food source: Geochemical evidence from the Coon Creek Lagerstätte in the Mississippi Embayment
Authors: Vrazo M. B. , Diefendorf A. F. , Crowley B. E. , Czaja A. D.
Published: January 2018

The Upper Cretaceous Coon Creek Lagerstätte of Tennessee, USA, is known for its extremely well‐preserved mollusks and decapod crustaceans. However, the depositional environment of this unit, particularly its distance to the shoreline, has long been equivocal. To better constrain the coastal proximity of the Coon Creek Formation, we carried out a multiproxy geochemical analysis of fossil decapod (crab, mud shrimp) cuticle and associated sediment from the type section. Elemental analysis and Raman spectroscopy confirmed the presence of kerogenized carbon in the crabs and mud shrimp; carbon isotope (δ13C) analysis of bulk decapod cuticle yielded similar mean δ13C values for both taxa (−25.1‰ and −26‰, respectively). Sedimentary biomarkers were composed of n‐alkanes from C16 to C36, with the short‐chain n‐alkanes dominating, as well as other biomarkers (pristane, phytane, hopanes). Raman spectra and biomarker thermal maturity indices suggest that the Coon Creek Formation sediments are immature, which supports retention of unaltered, biogenic isotopic signals in the fossil organic carbon remains. Using our isotopic results and published calcium carbonate δ13C values, we modeled carbon isotope values of carbon sources in the Coon Creek Formation, including potential marine (phytoplankton) and terrestrial (plant) dietary sources. Coon Creek Formation decapod δ13C values fall closer to those estimated for terrigenous plants than marine phytoplankton, indicating that these organisms were feeding primarily on terrigenous organic matter. From this model, we infer that the Coon Creek Formation experienced significant terrigenous organic matter input via a freshwater source and thus was deposited in a shallow, nearshore marine environment proximal to the shoreline. This study helps refine the paleoecology of nearshore settings in the Mississippi Embayment during the global climatic shift in the late Campanian–early Maastrichtian and demonstrates for the first time that organic δ13C signatures in exceptionally preserved fossil marine arthropods are a viable proxy for use in paleoenvironmental reconstructions.
Highly dynamic wintering strategies in migratory geese: Coping with environmental change
Authors: Clausen Kevin K. , Madsen Jesper , Cottaar Fred , Kuijken Eckhart , Verscheure Christine
Published: January 2018

When and where to move is a fundamental decision to migratory birds, and the fitness‐related costs and benefits of migratory choices make them subject to strong selective forces. Site use and migration routes are outcomes of opportunities in the surrounding landscape, and the optimal migration strategy may be conservative or explorative depending on the variability in the environment occupied by the species. This study applies 25 years of resighting data to examine development in winter migration strategy of pink‐footed geese divided among Denmark, the Netherlands and Belgium, and analyse potential drivers of strategy change as well as individuals’ likelihood to break with migratory tradition. Contrary with the general notion that geese are highly traditional in their winter site use, our results reveal that winter migration strategy is highly dynamic in this species, with an average annual probability of changing strategy of 54%. Strategy was not related to hunting pressure or winter temperature, but could be partly explained by a tracking of food resources in a landscape of rapid land use changes. The probability of individuals changing strategy from year to year varied considerably between birds, and was partly related to sex and age, with young males being the most likely to change. The annual probability of changing wintering strategy increased substantially from ≈40% to ≈60% during the study period, indicating an increasingly explorative behaviour. Our findings demonstrate that individual winter strategies are very flexible and able to change over time, suggesting that phenotypic plasticity and cultural transmission are important drivers of strategy choice in this species. Growing benefits from exploratory behaviours, including the ability to track rapid land use changes, may ultimately result in increased resilience to global change.
Leveraging symbolic capital: the use of blat networks across transnational spaces
Authors: RODGERS PETER , VERSHININA NATALIA , WILLIAMS COLIN C. , THEODORAKOPOULOS NICK
Published: January 2018

In this article, we contribute to debates on how social networks sustain migrants' entrepreneurial activities. By reporting on 31 interviews with Eastern European migrants in the UK, we provide a critical lens on the tendency to assume that migrants have ready‐made social networks in the host country embedded in co‐ethnic communities. We extend this limited perspective by demonstrating how Eastern European migrants working in the UK transform blat social networks, formulated in the cultural and political contours of Soviet society, in their everyday lived experiences. Our findings highlight not only the monetarization of such networks but also the continuing embedded nature of trust existing within these networks, which cut across transnational spaces. We show how forms of social capital based on Russian language use and legacies of a shared Soviet past, are just as important as the role of ‘co‐ethnics’ and ‘co‐migrants’ in facilitating business development. In doing so, we present a more nuanced understanding of the role that symbolic capital plays in migrant entrepreneurial journeys and its multifaceted nature.
National audit of perinatal HIV infections in the UK, 2006–2013: what lessons can be learnt?
Authors: Peters H , Thorne C , Tookey PA , Byrne L
Published: January 2018

Objectives

The aim of the study was to investigate circumstances surrounding perinatal transmissions of HIV (PHIVs) in the UK.

Methods

The National Study of HIV in Pregnancy and Childhood conducts comprehensive surveillance of all pregnancies in women diagnosed with HIV infection and their infants in the UK; reports of all HIV‐diagnosed children are also sought, regardless of country of birth. Children with PHIV born in 2006–2013 and reported by 2014 were included in an audit, with additional data collection via telephone interviews with clinicians involved in each case. Contributing factors for each transmission were identified, and cases described according to main likely contributing factor, by maternal diagnosis timing.

Results

A total of 108 PHIVs were identified. Of the 41 (38%) infants whose mothers were diagnosed before delivery, it is probable that most were infected in utero, around 20% intrapartum and 20% through breastfeeding. Timing of transmission was unknown for most children of undiagnosed mothers. For infants born to diagnosed women, the most common contributing factors for transmission were difficulties with engagement and/or antiretroviral therapy (ART) adherence in pregnancy (14 of 41) and late antenatal booking (nine of 41); for the 67 children with undiagnosed mothers, these were decline of HIV testing (28 of 67) and seroconversion (23 of 67). Adverse social circumstances around the time of pregnancy were reported for 53% of women, including uncertain immigration status, housing problems and intimate partner violence. Eight children died, all born to undiagnosed mothers.

Conclusions

Priority areas requiring improvement include reducing incident infections, improving ART adherence and facilitating better engagement in care, with attention to addressing the health inequalities and adverse social situations faced by these women.
Treatment with low doses of aspirin during chronic phase of experimental Chagas’ disease increases oesophageal nitrergic neuronal subpopulation in mice
Authors: Massocatto Cristina Lorena , Martins Moreira Neide , Muniz Eliane , Marques de Araújo Silvana , Pinge‐filho Phileno , Rossi Robson Marcelo , de Almeida Araújo Eduardo José , de Mello Gonçales Sant'ana Débora
Published: January 2018

Patients with Chagas’ disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas’ disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas’ disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas’ disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology.
MAIT cells and viruses
Authors: Ussher James E , Willberg Christian B , Klenerman Paul
Published: January 2018

Mucosal associated invariant T cells (MAIT cells) bear a T cell receptor (TCR) that specifically targets microbially derived metabolites. Functionally, they respond to bacteria and yeasts, which possess the riboflavin pathway, essential for production of such metabolites and which are presented on MR1. Viruses cannot generate these ligands, so a priori, they should not be recognized by MAIT cells and indeed this is true when considering recognition through the TCR. However, MAIT cells are distinctive in another respect, since they respond quite sensitively to non‐TCR signals, especially in the form of inflammatory cytokines. Thus, a number of groups have shown that virus infection can be “sensed” by MAIT cells and a functional response invoked. Since MAIT cells are abundant in humans, especially in tissues such as the liver, the question has arisen as to whether this TCR‐independent MAIT cell triggering by viruses plays any role in vivo. In this review, we will discuss the evidence for this phenomenon and some common features which emerge across different recent studies in this area.
Fathers’ experiences with their preterm babies admitted to neonatal intensive care unit: A multi‐method study
Authors: Stefana Alberto , Padovani Ezio Maria , Biban Paolo , Lavelli Manuela
Published: January 2018

Aim

The aim of this study was to investigate fathers’ emotional experiences of their infant's preterm birth and subsequent stay in neonatal intensive care unit.

Background

When a baby is born preterm, there is also the premature interruption of the process of preparation for fatherhood. As a result, the impact on fathers of the preterm birth can bring negative consequences for the development of father–infant relationship.

Design

A multi‐method approach was used which included ethnographic observation, semi‐structured interviews with fathers, a self‐report questionnaire and clinical information between September 2015–March 2017.

Method

Data were analysed using a mixed‐method: a thematic analysis of data from the interviews and quantitative analyses to detect possible clusters of fathers’ emotional experiences and associations between clusters and fathers’ and/or infants’ characteristics.

Results

Two clusters were identified. The “fathers‐of‐preterm‐infants” touched their baby as soon as they were given the opportunity and without fear that they would harm their infant. They were struck by their baby's physical appearance. In contrast, the “preterm fathers” preferred not to touch their baby when first given the chance, for fear of breaking/damaging/infecting her/him. They were struck both by the baby's physical appearance and by the technology/equipment around her/him and were afraid that their infant would die. All the “fathers‐of‐preterm‐infants”, but only just over half of the “preterm fathers”, were actively engaged in their infant's care. Clusters were associated with the infant's gestational age.

Conclusion

Fathers of preterm infants should receive personalized support specifically addressed to them and based on the infant's gestational age.
Histiocytosis – cutaneous manifestations of hematopoietic neoplasm and non‐neoplastic histiocytic proliferations
Authors: Luder C.M. , Nordmann T.M. , Ramelyte E. , Mühleisen B. , Kerl K. , Guenova E. , Dummer R.
Published: January 2018

Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions, while in others, the skin is rarely involved. Here, we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai–Dorfman disease (RDD) and related histiocytoses (R group) according to the current classification. Characteristic clinical presentations noted were a rust‐brown colour or xanthomatous aspect in many cases of histiocytoses. Histological criteria for differentiation are described. Immunohistochemistry shows positivity for S100 and CD1a in Langerhans‐cell histiocytoses (LHCH) of the L group, while CD68 positivity with S100 and CD1a negativity are typical in histiocytoses of the C group of cutaneous and mucocutaneous histiocytoses. RDD in the R group shows positivity for S100 and CD68, while CD1a is negative. We further review the pathogenesis of LHCH based on insights on the central role of the mitogen‐activated protein (MAPK) kinase pathway. Common mutations in various histiocytic populations of diverse ontogeny and at different stages of differentiation may be responsible for the diverse clinical picture of this neoplastic entity. For histiocytoses of the C group and R group, a reactive origin is discussed with the exception of the disseminated form of juvenile xanthogranuloma. We suggest exploring the role of an origin from skin residing histiocytes for the isolated cutaneous manifestation in some types. With regard to therapeutic options, skin‐directed therapies are the first choice in limited disease, while systemic chemotherapy has traditionally been used in extensive disease. In Langerhans‐cell histiocytoses and related entities, therapy by BRAF inhibition has led to a breakthrough especially in patients with an activation of the MAPK pathway.
Efficacy and toxicity of praziquantel in helminth‐infected barbel (Barbus barbus L.)
Authors: Zuskova E , Piackova V , Machova J , Chupani L , Steinbach C , Stara A , Velisek J
Published: January 2018

This study evaluated efficacy and toxicity of the pyrazinoisoquinoline anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of Diplostomum spathaceum and adult Pomphorhynchus laevis, and assessed antioxidant biomarkers and the lipid peroxidation response in juvenile barbel post‐treatment. The estimated 96‐hr LC50 of PZQ was 28.6 mg/L. For evaluation of efficacy, barbel naturally infected with D. spathaceum were exposed to a 10 and 20 mg/L PZQ 4‐day bath treatment. Both concentrations were 100% effective against D. spathaceum and significantly (p < .01) affected the activity of catalase, superoxide dismutase, glutathione reductase and glutathione‐S‐transferase as well as levels of reduced glutathione in liver and muscle. The efficacy of orally administered PZQ was assessed in adult barbel naturally infected with P. laevis. Fish were administered 10, 30 and 50 mg/kg of body weight and examined via gut dissection after 6 days. The 50 mg/kg dose significantly decreased the intensity of infection. Praziquantel is a feasible bath treatment for barbel infected with D. spathaceum and has potential for oral treatment of broodfish infected with P. laevis.
Inflammatory biomarkers and intellectual disability in patients with Down syndrome
Authors: Manti S. , Cutrupi M. C. , Cuppari C. , Ferro E. , Dipasquale V. , Di Rosa G. , Chimenz R. , La Rosa M. A. , Valenti A. , Salpietro V.
Published: January 2018

Background

Intellectual disability (ID) is part of the Down syndrome (DS) phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals with DS is not yet fully understood, with many research hypotheses still unproven. Basing on previous studies (which suggested a possible role of altered inflammatory response in DS‐related ID), we assessed the serum levels of a number of inflammatory biomarkers [serum amyloid A (SAA), C‐reactive protein (C‐RP), high mobility group box‐1 (HMGB1)] in a cohort of individuals with DS and healthy controls.

Methods

In total, 24 children diagnosed with DS and 12 healthy controls were enrolled, and all underwent detailed cognitive assessment. Also, serum SAA, C‐RP and HMGB1 levels were measured in all recruited subjects and correlated to the severity of ID in the DS group.

Results

Serum SAA, C‐RP and HMGB1 values were found to be significantly higher in the DS group compared with the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively correlated with C‐RP and SAA in the DS group but not in the healthy controls. Only serum C‐RP levels resulted inversely correlated (P < 0.01) with intelligence quotient (IQ); conversely, significant statistical correlations between serum SAA levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05).

Conclusions

The levels of the determined markers were higher in DS individuals compared with (cognitively) healthy subjects, and CRP showed a negative correlation with IQ in children with DS.
Genetic removal of eIF2α kinase PERK in mice enables hippocampal L‐LTP independent of mTORC1 activity
Authors: Zimmermann Helena R. , Yang Wenzhong , Beckelman Brenna C. , Kasica Nicole P. , Zhou Xueyan , Galli Lucas Dufresne , Ryazanov Alexey G. , Ma Tao
Published: January 2018

Characterization of the molecular signaling pathways underlying protein synthesis‐dependent forms of synaptic plasticity, such as late long‐term potentiation (L‐LTP), can provide insights not only into memory expression/maintenance under physiological conditions but also potential mechanisms associated with the pathogenesis of memory disorders. Here, we report in mice that L‐LTP failure induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) inhibitor rapamycin is reversed by brain‐specific genetic deletion of PKR‐like ER kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2α (eIF2α). In contrast, genetic removal of general control non‐derepressible‐2, GCN2 (GCN2 KO), another eIF2α kinase, or treatment of hippocampal slices with the PERK inhibitor GSK2606414, does not rescue rapamycin‐induced L‐LTP failure, suggesting mechanisms independent of eIF2α phosphorylation. Moreover, we demonstrate that phosphorylation of eukaryotic elongation factor 2 (eEF2) is significantly decreased in PERK KO mice but unaltered in GCN2 KO mice or slices treated with the PERK inhibitor. Reduction in eEF2 phosphorylation results in increased general protein synthesis, and thus could contribute to the mTORC1‐independent L‐LTP in PERK KO mice. We further performed experiments on mutant mice with genetic removal of eEF2K (eEF2K KO), the only known kinase for eEF2, and found that L‐LTP in eEF2K KO mice is insensitive to rapamycin. These data, for the first time, connect reduction in PERK activity with the regulation of translation elongation in enabling L‐LTP independent of mTORC1. Thus, our findings indicate previously unrecognized levels of complexity in the regulation of protein synthesis‐dependent synaptic plasticity.

image

Read the Editorial Highlight for this article on page 119.

Cover Image for this issue: doi: 10.1111/jnc.14185.
Efficacy of photodynamic therapy in the treatment of symptomatic oral lichen planus: A systematic review
Authors: Al‐Maweri Sadeq Ali , Ashraf Sajna , Kalakonda Butchibabu , Halboub Esam , Petro Waleed , AlAizari Nader Ahmed
Published: January 2018

Background

The aim of this study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of symptomatic oral lichen planus (OLP).

Materials and Methods

PubMed/MEDLINE, Scopus, and ISI Web of knowledge were searched until July 2017, using the following keywords: OLP, erosive lichen planus, lichen planus, and PDT.

Results

Five clinical studies were included. The risk of bias was considered high in 4 studies and moderate in 1 study. The efficacy of PDT was compared with topical corticosteroids in all included studies. Laser wavelengths, duration of irradiation, and power density ranged between 420‐660 nm, 30 seconds to 10 minutes, and 10‐500 mW/cm2, respectively. All studies reported PDT to be effective in the management of symptomatic OLP. Two studies reported PDT to be as effective as corticosteroids, 1 study reported a better efficacy of PDT compared to corticosteroids, whereas 2 studies found PDT to be inferior to corticosteroids.

Conclusions

The limited available evidence suggests that PDT is an effective treatment option for the management of OLP. However, due to the limited number of studies included in this review and heterogeneity among these studies, more well‐designed clinical trials with adequate sample sizes are highly warranted.
Transcriptome analysis identifies candidate genes associated with melanin and toxin biosynthesis and pathogenicity of the maize pathogen, Curvularia lunata
Authors: Gao Jin‐Xin , Chen Jie
Published: January 2018

In our previous study, we have successfully cloned and deleted the pks18 gene, which is involved in 1,8‐dihydroxynaphthalene melanin and methyl 5‐(hydroxymethyl) furan‐2‐carboxylate toxin production and in the pathogenicity of Curvularia lunata. Moreover, we hypothesized that other genes may also be related to the melanin and toxin production, or pathogenicity. In this study, a transcriptome approach based on the RNA‐Seq technique was used to identify specific genes associated with pks18 expression in pks18 deletion mutant ∆PKS18 and wild‐type CX‐3. A total of 137 overexpressed and 221 underexpressed genes were successfully identified in ∆PKS18. The NADPH–cytochrome P450 reductase gene CL00874, alcohol dehydrogenase gene CL02247 and L‐lactate dehydrogenase gene CL08767 may be required for the production of melanin and toxin. 1,4‐Beta‐D‐glucan cellobiohydrolase gene CL04068, ribonuclease III gene CL00399, salicylate hydroxylase gene CL00458 and tri14‐like protein gene CL00462 may contribute to the pathogenicity of C. lunata. Alternative splicing (AS) analysis revealed that over 76.15% of AS events involve the intron retention. This comprehensive transcriptomic analysis provides a key resource for understanding the molecular basis of melanin and toxin formation and for further elucidating the pathogenicity of C. lunata.
A distinct group of north European Aedes vexans as determined by mitochondrial and nuclear markers
Authors: Lilja T. , Troell K. , Kirik H. , Lindström A.
Published: January 2018

The floodwater mosquito Aedes (Aedimorphus) vexans (Meigen, 1830) (Diptera: Culicidae) is common in several areas of Sweden and is predicted to become more abundant in the wake of expected changes in precipitation and temperature caused by climate change. As well as being a nuisance, Ae. vexans can act as a vector of over 30 viruses. In the event of an outbreak of disease caused by a vector‐borne virus, knowledge of the distribution, population structure and intermixing of populations from different locations will help direct resources to target locations to prevent spread of the pathogen. The present study analysed individual Ae. vexans from eight locations throughout Sweden. Based on the mitochondrial cytochrome oxidase I (COI) marker, a subset of the analysed mosquitoes cluster apart from the other samples. Similarly, two nuclear loci were sequenced and the same phylogenetic structure observed. These results indicate that this group represents a reproductively isolated population among Ae. vexans. Comparisons with COI sequences held in the Barcode of Life Database (BoLD) for Ae. vexans from around the world show that specimens collected in Belgium and Estonia group together with the Swedish group, suggesting that this genotype is present throughout northern Europe. These results suggest there is a cryptic taxonomic unit related to Ae. vexans in northern Europe.
Collaborative child home injury prevention in Thailand: An action research study
Authors: Machin Alison I. , Ngamsuoy Amornrat , Pearson Pauline
Published: January 2018

Child home accidental injury is a global health issue, and promoting child safety is a pediatric nursing challenge worldwide. Planning child home accidental injury prevention requires understanding of factors influencing parents’ behavior. Evidence suggests that participatory health promotion positively influences behavior; however, research on Thai parents is limited. This qualitative, action research study aimed to understand Thai parents’ experiences of participating in a collaborative child home accidental injury prevention program and its influence on their behavior. Eight parental mother/father couples from one Thai province consented to participate, providing a wide range of data via in‐depth individual interviews and self‐assessment questionnaires. Thematic analysis of interview transcripts yielded three themes: collaborative learning, parental behavior change, and reflective learning extends beyond families. Participants reported that workshop participation improved their child home accidental injury‐prevention behavior. The present study can inform pediatric nursing, child health‐care practice, and child health policy in Thailand and beyond.
Is overweight/obesity a risk factor for periodontitis in young adults and adolescents?: a systematic review
Authors: Khan S. , Barrington G. , Bettiol S. , Barnett T. , Crocombe L.
Published: January 2018

Background

Obesity in young adults and adolescents is associated with chronic co‐morbidities. This project investigated whether being overweight or obese is a risk factor for periodontitis in adolescents (13–17 years) and young adults (18–34 years).

Methods

A search of 12 databases was conducted using Medical Subject Headings/Index and Emtree terms. Based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses, articles published between 2003 and 2016 were screened that reported periodontal and anthropometric measures. The Newcastle‐Ottawa Scale was used to appraise the quality of studies.

Results

Of 25 eligible studies from 12 countries, 17 showed an association between obesity and periodontitis (odds ratios ranged from 1.1 to 4.5). The obesity indicators of body mass index, waist circumference, waist‐hip ratio and body fat percentage were significantly associated with measures of periodontitis of bleeding on probing, plaque index, probing depths, clinical attachment loss, calculus, oral hygiene index and community periodontal index. Two prospective cohort studies in the review showed no significant association between obesity and periodontitis, but these studies had limitations of study design and used inappropriate epidemiological diagnostic measures of periodontitis.

Conclusion

There was evidence to suggest that obesity is associated with periodontitis in adolescents and young adults.

Systematic Review Registration: PROSPERO Registration Number: CRD42016046507
Technical note: A clinical skills teaching‐aid for paediatric minor oral surgery
Authors: Foley J.I. , McDonald A.
Published: January 2018

Aim

To describe the preparation of a cost‐effective teaching model for paediatric minor surgical procedures.

Material and methods

A surgical simulator for paediatric minor oral surgery for supernumerary‐/canine removal, incisor‐/canine exposure and bonding was created using an impression of a KaVo model in to which Formula Dentsone was poured following the positioning of plastic teeth in to ectopic positions. To simulate soft tissue, a layer of Dentsply Aquasil™ Ultra Monophase Smart Wetting® Impression Material of medium‐body consistency was injected around the gingival margins of the teeth and over the labial/buccal stone and palatal regions.

Results

The cost/model for the surgical simulator approximated €10, a considerable saving on the commercially available products.

Conclusions

Such a surgical simulator can be readily constructed by institutional Laboratory Services to provide a relatively inexpensive teaching aid for paediatric minor oral surgical procedures.
Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS)
Authors: Lee J. Y. , Kim M. , Yang H.‐K. , Kim H. M. , Cho J. , Kim Y.‐M. , Lim I. S. , Cheong H.‐K. , Kim H. S. , Sohn I. , Kim J. , Ahn K.
Published: January 2018

Background

We have developed the Atopic Dermatitis Symptom Score (ADSS) by which patients or parents can easily assess and record AD symptoms on a daily basis in a smartphone application. The aim of this study was to evaluate the reliability and validity of the ADSS.

Methods

We enrolled 307 children and adolescents with AD. Parents or caregivers were asked to record daily symptoms of the patients (itching, sleep disturbance, erythema, dryness, oozing, and edema) using a scale of 0‐4. Statistical analyses consisted of the test‐retest reliability, concurrent validity, minimal clinically important difference (MCID), responsiveness, floor or ceiling effects, and screening accuracy. Receiver‐operating characteristic analyses were conducted to evaluate the ADSS cutoff point for predicting severe AD (SCORing AD [SCORAD] ≥40).

Results

Test‐retest reliability between daytime and night‐time ADSS was good (intraclass correlation coefficient, 0.82 [95% CI: 0.70‐0.90]). An increase in ADSS was significantly associated with an increase in SCORAD (r = 0.64, P < .0001) (concurrent validity). The MCID was 4.1 points for the ADSS. There was a significant association between changes in ADSS and SCORAD (r = 0.56, P < .0001), indicating good responsiveness. At the optimal ADSS cutoff value of 7.0, sensitivity, specificity, and positive and negative predictive values were 88.4%, 78.6%, 21.1%, and 99.1%, respectively (screening accuracy).

Conclusions

The ADSS can be a useful tool for self‐assessment of skin symptoms in children with AD.