bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal stromal cells from Shwachman‐Diamond syndrome patients fail to recreate a bone marrow niche in vivo and exhibit impaired angiogenesis
Authors: Bardelli Donatella , Dander Erica , Bugarin Cristina , Cappuzzello Claudia , Pievani Alice , Fazio Grazia , Pierani Paolo , Corti Paola , Farruggia Piero , Dufour Carlo , Cesaro Simone , Cipolli Marco , Biondi Andrea , D'Amico Giovanna
Published: May 2018

Shwachman‐Diamond syndrome (SDS) is a rare multi‐organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS‐MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model. We show that the ability of semi‐cartilaginous pellets (SCPs) derived from SDS‐MSCs to generate complete heterotopic ossicles in vivo is severely impaired in comparison with HD‐MSC‐derived SCPs. Specifically, after in vitro angiogenic stimuli, SDS‐MSCs showed a defective ability to form correct networks, capillary tubes and vessels and displayed a marked decrease in VEGFA expression. Altogether, these findings unveil a novel mechanism of SDS‐mediated haematopoietic dysfunction based on hampered ability of SDS‐MSCs to support angiogenesis. Overall, MSCs could represent a new appealing therapeutic target to treat dysfunctional haematopoiesis in paediatric SDS patients.
Salt, inflammation, IL‐17 and hypertension
Authors: Wenzel Ulrich O , Bode Marlies , Kurts Christian , Ehmke Heimo
Published: May 2018

Traditionally, arterial hypertension and subsequent end‐organ damage have been attributed to haemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign microorganisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Over the past few years, important findings have revolutionized hypertension research. Firstly, in 2007, a seminal paper showed that adaptive immunity is involved in the pathogenesis of hypertension. Secondly, salt storage in the skin and its consequences for cardiovascular physiology were discovered. Thirdly, after the discovery that salt promotes the differentiation of CD4+ T cells into TH17 cells, it was demonstrated that salt directly changes several cells of the innate and adaptive immune system and aggravates autoimmune disease but may improve antimicrobial defence. Herein, we will review pathways of activation of immune cells by salt in hypertension as the framework for understanding the multiple roles of salt and immunity in arterial hypertension and autoimmune disease.

Linked Articles

This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation
Authors: Vekariya Mayur K. , Vekariya Rajesh H. , Brahmkshatriya Pathik S. , Shah Nisha K.
Published: May 2018

A series of new pyrimidine‐pyrazole hybrid molecules were designed as inhibitors of cyclin‐dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2‐CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50 < 20 nm); which can be further optimized to have selectivity over other kinase isoforms.
Cyberbullying prevention: Insight and recommendations from youths, parents, and paediatricians
Authors: Mehari K. R. , Moore W. , Waasdorp T. E. , Varney O. , Berg K. , Leff S. S.
Published: May 2018

Background

The purpose of this study was to identify injunctive norms for cyberbullying prevention among youths, parents, and primary care providers, as well as barriers to preventive behaviours.

Methods

Semi‐structured interviews on the topic of cyberbullying were conducted with 29 adolescents, 13 paediatricians, and 15 parents recruited from 3 primary care sites. Transcripts were coded for themes related to various stakeholders' perceived roles in cyberbullying prevention and barriers to preventive behaviours.

Results

Participants reported perceptions that youths should intervene in the moment and get outside help for others. Fear of repercussions emerged as a significant barrier to these behaviours. Participants believed that parents should communicate with their children and monitor and supervise youths' online activities. Barriers included perception of priority and low parental efficacy or naiveté. Participants believed that providers should provide education and resources and ask screening questions; the most frequently identified barrier to those behaviours was the perception of providers' role.

Conclusions

Youths and providers may not be aware of their potential to prevent cyberbullying before it occurs. Educating youths, parents, and providers about cyberbullying prevention is warranted.
Children's experiences with an intervention aimed to prevent further physical abuse
Authors: Thulin Johanna , Kjellgren Cecilia , Nilsson Doris
Published: May 2018

Although many children across cultures are victims of physical abuse, few treatment models target these children and their parents. In Sweden, Combined Parent–Child Cognitive Behavioural Therapy for families at risk for child physical abuse has been successfully used according to pretreatment and posttreatment studies. However, few studies have explored how physically abused children experience treatment. This study includes 20 physically abused children aged 9–17 who completed Combined Parent–Child Cognitive Behavioural Therapy. Children had a positive overall impression of the treatment and highlighted addressing the abuse, as well as processing their experiences as particularly essential. Children described a positive transformation in their family life as a result of treatment, including violence cessation and bonding among family members. Children experienced the intervention as inclusive and child‐friendly. The implications of the promising findings are discussed.
Challenges of operationalizing trauma‐informed practice in child protection services in New Zealand
Authors: Atwool Nicola
Published: May 2018

New Zealand is undergoing major change in service delivery to children and families. A new Ministry for Children Oranga Tamariki has been established to oversee 5 work streams, one of which provides intensive intervention with families requiring a statutory response to child protection concerns. The government minister responsible promised that the service would be child‐centred and trauma‐informed. To date, these terms remain undefined, and there is no shared understanding of their meaning. Practice frameworks to support the work of the new ministry are still being developed, creating something of a vacuum in the meantime. The focus of this paper is the challenge of implementing trauma‐informed practice in the child protection service provided by the Intensive Intervention work stream. Limited research or commentary on trauma‐informed practice in this context currently exists. Drawing on the relevant available literature, the concept and its application in child protection social work is explored. An ecological framework is used to discuss the changes needed to achieve this. Particular attention is paid to the impact of historical trauma for indigenous people due to New Zealand's colonial history and their over‐representation in care and protection services.
Organic psychosis: The pathobiology and treatment of delusions
Authors: Joyce Eileen Maria
Published: May 2018

Organic or secondary psychosis can be seen in diverse conditions such as toxic/metabolic disorders, neurodegenerative disease, and stroke. Poststroke psychosis is a rare phenomenon, but its study has significantly contributed to the understanding of delusion formation. The evidence from case studies of patients with focal strokes shows that delusions develop following unilateral damage of the right hemisphere. The majority of patients with right hemisphere stroke do not develop delusions however, and advanced neuroimaging analysis has elucidated why this symptom develops in only a small proportion. Lesions of the right lateral prefrontal cortex or lesions with connectivity to this area correlate with delusional beliefs in this subgroup. Studies of patients with primary psychosis, for example schizophrenia, or under the influence of the psychotogenic drug ketamine, also show abnormal function of this area in relation to the severity of their abnormal beliefs. The conclusion of these studies is that the right lateral prefrontal cortex is 1 hub in a neural network which includes the basal ganglia and limbic system and receives inputs from midbrain dopamine neurones. In patients with schizophrenia, or at risk of psychosis, dopamine is dysregulated and evidence suggests that faulty dopamine signaling is the precursor of delusion formation. It is therefore likely that the mechanism of delusion formation is the same in both primary and secondary psychosis. This is consistent with the mainstay of treatment of both conditions being antipsychotic medication. However, antipsychotic medication in people with cerebrovascular disease should be avoided if at all possible. This is because epidemiological studies have found that antipsychotic use is associated with an increased risk of stroke and will thus compound the possibility of a further cerebrovascular accident.
Change of signs, symptoms and voice quality evaluations throughout a 3‐ to 6‐month empirical treatment for laryngopharyngeal reflux disease
Authors: Lechien J.R. , Finck C. , Khalife M. , Huet K. , Delvaux V. , Picalugga M. , Harmegnies B. , Saussez S.
Published: May 2018

Objective

To assess the usefulness of voice quality measurements as a treatment outcome in patients with laryngopharyngeal reflux (LPR)‐related symptoms.

Design

Prospective uncontrolled multi‐centre study.

Material and methods

A total of 80 clinically diagnosed LPR patients with a reflux finding score (RFS)>7 and a reflux symptom index (RSI)>13 were treated with pantoprazole and diet recommendations during 3 or 6 months, according to their evolution. RSI; RFS; blinded Grade, Roughness, Breathiness, Asthenia, Strain and Instability (GRBASI) and aerodynamic and acoustic measurements were evaluated at baseline, 3 months (n = 80), and 6 months (n = 41) post‐treatment. We conducted a correlation analysis between the adherence to the diet, and the evolution of both signs and symptoms and between videolaryngostroboscopic signs and acoustic measurements.

Results

Reflux symptom index, RFS, perceptual voice quality evaluations (dysphonia, roughness, strain and instability), and aerodynamic and acoustic measurements (ie, percent jitter and percent shimmer) were significantly improved at 3 months post‐treatment but not at 6 months. Percent jitter was the most useful outcome for evaluating the clinical evolution of patients throughout the treatment course. A significant relationship between globus sensation and posterior commissure hypertrophy was documented; both seemed to significantly improve from 3 to 6 months. The correlation analysis revealed correlations between adherence to diet recommendations and the improvement of symptoms and between posterior commissure granulation severity and acoustic measurement impairments.

Conclusion

Voice quality improved in a manner similar to both signs and symptoms throughout a 6‐month empirical treatment with better improvement the 3 first months. Voice quality assessments can be used as indicators of treatment effectiveness in patients with LPR‐related symptoms.
Cochlear implant performance in children deafened by congenital cytomegalovirus—A systematic review
Authors: Kraaijenga V.J.C. , Van Houwelingen F. , Van der Horst S.F. , Visscher J. , Huisman J.M.L. , Hollman E.J. , Stegeman I. , Smit A.L.
Published: May 2018

Background

Congenital cytomegalovirus (cCMV) infection is a major cause of sensorineural hearing loss in children.

Objective of review

The objective of this systematic review was to compare performance in paediatric cochlear implant users with SNHL caused by cCMV compared to non‐cCMV implantees.

Type of review

Systematic review

Search strategy

PubMed, EMBASE and the Cochrane databases were searched from inception up to 15 May 2017 for children, cochlear implant, performance and their synonyms.

Evaluation methods

Titles, abstracts and full texts were screened for eligibility. Directness of evidence and risk of bias were assessed. From the included studies, study characteristics and outcome data (speech perception, speech production, receptive language and auditory performance of cCMV groups and non‐cCMV groups) were extracted.

Results

A total of 5280 unique articles were screened of which 28 were eligible for critical appraisal. After critical appraisal, 12 studies remained for data extraction. Seven of 12 studies showed worse performance after cochlear implantation in cCMV children compared to non‐cCMV children. Worse performance in cCMV children was attributed to cCMV‐related comorbidities in six of these studies. Available data on asymptomatic cCMV children compared to non‐cCMV children did not reveal an unfavourable effect on cochlear implant performance.

Conclusions

The available evidence reveals that cCMV children often have worse cochlear implant performance compared to non‐cCMV children, which can be attributed to cCMV related comorbidities. We urge physicians to take into account the cCMV related comorbidities in the counselling of paediatric CI users deafened by cCMV.
Management of early pouch‐related septic complications in ulcerative colitis: a systematic review
Authors: Worley G. H. T. , Segal J. P. , Warusavitarne J. , Clark S. K. , Faiz O. D.
Published: May 2018

Aim

It is well established that ileo‐anal pouch‐related septic complications (PRSC) increase the risk of pouch failure. There are a number of publications that describe the management of earlyPRSCin ulcerative colitis (UC) in small series. This article aims to systematically review and summarize the relevant current data on this subject and provide an algorithm for the management of earlyPRSC.

Method

A systematic review was undertaken in accordance withPRISMAguidelines. Studies published between 2000 and 2017 describing the clinical management ofPRSCin patients withUCwithin 30 days of primary ileo‐anal pouch surgery were included. A qualitative analysis was undertaken due to the heterogeneity and quality of studies included.

Results

A total of 1157 abstracts and 266 full text articles were screened. Twelve studies were included for analysis involving a total of 207 patients. The studies described a range of techniques including image‐guided, endoscopic, surgical and endocavitational vacuum methods. Based on the evidence from these studies, an algorithm was created to guide the management of earlyPRSC.

Conclusion

The results of this review suggest that although successful salvage of earlyPRSCis improving there is little information available relating to methods of salvage and outcomes. Novel techniques may offer an increased chance of salvage but comparative studies with longer follow‐up are required.
Further options for treating lipids in people with diabetes: targeting LDL‐cholesterol and beyond
Authors: Wierzbicki A. S.
Published: May 2018

Diabetes is associated with increased cardiovascular disease (CVD) risk. Previous studies with statins have established that a 1 mmol/l reduction in LDL‐cholesterol reduces CVD events by 21% over 5 years in people with diabetes. More recently, trials in people with acute coronary syndromes showed that ezetimibe reduced CVD events by 6% at 5 years and achieved a LDL‐cholesterol of 1.6 mmol/l with better results in people with Type 2 diabetes. Several novel lipid‐lowering therapies have recently been developed. Most data have been accumulated with proprotein convertase subtilisin kexin‐9 (PCSK‐9) inhibitors, which reduce LDL‐cholesterol by 50–55%. A large CVD outcome trial with evolocumab, in which 40% of participants had diabetes, achieved a LDL‐cholesterol of 0.8 mmol/l and showed a consistent 20% relative risk reduction within 2 years, including in people with diabetes. Trials to increase HDL‐cholesterol using cholesterol ester transfer protein (CETP) inhibitors have generally underwhelmed. Although anacetrapib reduced coronary ischaemic events by 7% in a population with chronic CVD, more expansive CVD endpoints were not improved. The complex nature of CETP inhibitor trial outcomes means that these compounds are not being developed further. Trials targeting inflammation‐associated lipids have been generally unsuccessful but recent data on the interleukin‐1B receptor antagonist canakinumab have shown a reduction in acute coronary intervention, validating this target although at the cost of increased infections. The ability to achieve low LDL‐cholesterol with off‐patent medications and the costs of novel therapies will confine the use of novel agents to subgroups of people at highest risk of CVD.
The effects of gestational diabetes mellitus on fetal growth and neonatal birth measures in an African cohort
Authors: Macaulay S. , Munthali R. J. , Dunger D. B. , Norris S. A.
Published: May 2018

Aim

Fetal exposure to gestational diabetes mellitus (GDM) is said to alter fetal growth and increase the risk of macrosomia. However, little research on GDM exists in African populations. This study aimed to assess longitudinal fetal growth and neonatal birth measures among Black African babies exposed to GDM.

Methods

Pregnant women (Soweto, South Africa) enrolled into a cohort study were followed up with repeated fetal ultrasounds. At 24–28 weeks’ gestation a 2‐h 75 g oral glucose tolerance test was performed and GDM was diagnosed using the World Health Organization's 2013 criteria. Neonatal birth measures were assessed.

Results

The study involved 741 women; 83 (11.2%) with GDM and 658 (88.8%) without. A total of 4040 fetal ultrasounds were performed. GDM exposure was associated with an increase in fetal growth measures, especially abdominal circumference, which was already seen at 16–18 weeks’ gestation. Male fetuses in particular, showed a significant association between GDM exposure and increased abdominal circumference (P = 0.009). Most women with GDM (66.3%) received management; all received diet therapy and 32.7% were prescribed medication. There was no difference in birth measures between the GDM‐exposed and unexposed neonates.

Conclusion

Repeated ultrasound measures identified the effects of GDM as early as 16–18 weeks’ gestation, well before a diagnosis of GDM would usually be made. Sex differences in fetal growth were observed, with GDM‐exposed male fetuses being more affected with larger abdominal circumferences than females. A low rate of macrosomia was observed compared with historical GDM populations.
Empagliflozin as add‐on to linagliptin in a fixed‐dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a 52‐week, randomized, placebo‐controlled trial
Authors: Kawamori Ryuzo , Haneda Masakazu , Suzaki Keiko , Cheng Gang , Shiki Kosuke , Miyamoto Yuki , Solimando Fernando , Lee Christopher , Lee Jisoo , George Jyothis
Published: May 2018

Aims

This double‐blind, randomized, placebo‐controlled trial (ClinicalTrials.gov NCT02453555) evaluated the efficacy and safety of empagliflozin (Empa) 10 or 25 mg as add‐on to linagliptin (Lina) 5 mg (fixed‐dose combination, Empa/Lina 10/5 or 25/5) in insufficiently controlled Japanese type 2 diabetes patients.

Methods

The trial (40 sites; May 2015‐March 2017) involved screening 433 adults (≥20 years) who were treatment‐naive or were using one oral antidiabetic drug for ≥12 weeks, which was discontinued at enrolment. Patients with HbA1c 7.5%‐10.0% after ≥16 weeks of using Lina (pre‐enrolment or during a 16‐week, open‐label period) and 2 weeks of using placebo (Plc) for Empa/Lina 10/5, plus Lina, were randomized (2:1) to once‐daily Empa/Lina 10/5 (n = 182) or Plc/Lina 10/5 (n = 93) for 24 weeks. Patients with HbA1c ≥ 7.0% at Week 24 received Empa/Lina up‐titrated to 25/5 (n = 126) or the corresponding placebo (n = 80), per randomization, from Week 28; 172 Empa/Lina and 84 Plc/Lina patients completed 52 weeks.

Results

Change from baseline in HbA1c was greater (P < .0001) with Empa/Lina than with Plc/Lina at Week 24 (primary outcome, −0.93% vs 0.21%; adjusted mean difference, −1.14%) and Week 52 (−1.16% vs 0.06%; adjusted mean difference, −1.22%). More patients with HbA1c < 7.0% and greater decreases in fasting plasma glucose, body weight and systolic blood pressure were seen in the Empa/Lina group than in the Plc/Lina group. Empa/Lina was well tolerated. The adverse events that were more frequent with Empa/Lina were known empagliflozin‐associated events (eg, increased urination, increased blood ketones). There were no adjudication‐confirmed diabetic ketoacidosis events or lower limb amputations.

Conclusions

These results support the notion that empagliflozin‐linagliptin in fixed‐dose combination is a therapeutic option for Japanese patients with type 2 diabetes.
Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials
Authors: Ahrén Bo , Atkin Stephen L. , Charpentier Guillaume , Warren Mark L. , Wilding John P. H. , Birch Sune , Holst Anders Gaarsdal , Leiter Lawrence A.
Published: May 2018

Aims

To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once‐weekly glucagon‐like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3‐6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contributing factors to weight loss are not established.

Materials and Methods

Subjects with inadequately controlled type 2 diabetes (drug‐naïve or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. Change from baseline in body weight was assessed within each trial and subgroup. A mediation analysis separated weight loss into direct or indirect (mediated by nausea or vomiting) effects.

Results

Clinically relevant weight‐loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects).

Conclusions

In SUSTAIN 1 to 5, semaglutide‐induced weight loss was consistently greater versus comparators, regardless of baseline BMI. The contribution of nausea or vomiting to this weight loss was minor.
The “isohydric trap”: A proposed feedback between water shortage, stomatal regulation, and nutrient acquisition drives differential growth and survival of European pines under climatic dryness
Authors: Salazar‐Tortosa Diego , Castro Jorge , Villar‐Salvador Pedro , Viñegla Benjamín , Matías Luis , Michelsen Anders , Rubio de Casas Rafael , Querejeta José I.
Published: May 2018

Climatic dryness imposes limitations on vascular plant growth by reducing stomatal conductance, thereby decreasing CO2 uptake and transpiration. Given that transpiration‐driven water flow is required for nutrient uptake, climatic stress‐induced nutrient deficit could be a key mechanism for decreased plant performance under prolonged drought. We propose the existence of an “isohydric trap,” a dryness‐induced detrimental feedback leading to nutrient deficit and stoichiometry imbalance in strict isohydric species. We tested this framework in a common garden experiment with 840 individuals of four ecologically contrasting European pines (Pinus halepensis, P. nigra, P. sylvestris, and P. uncinata) at a site with high temperature and low soil water availability. We measured growth, survival, photochemical efficiency, stem water potentials, leaf isotopic composition (δ13C, δ18O), and nutrient concentrations (C, N, P, K, Zn, Cu). After 2 years, the Mediterranean species Pinus halepensis showed lower δ18O and higher δ13C values than the other species, indicating higher time‐integrated transpiration and water‐use efficiency (WUE), along with lower predawn and midday water potentials, higher photochemical efficiency, higher leaf P, and K concentrations, more balanced N:P and N:K ratios, and much greater dry‐biomass (up to 63‐fold) and survival (100%). Conversely, the more mesic mountain pine species showed higher leaf δ18O and lower δ13C, indicating lower transpiration and WUE, higher water potentials, severe P and K deficiencies and N:P and N:K imbalances, and poorer photochemical efficiency, growth, and survival. These results support our hypothesis that vascular plant species with tight stomatal regulation of transpiration can become trapped in a feedback cycle of nutrient deficit and imbalance that exacerbates the detrimental impacts of climatic dryness on performance. This overlooked feedback mechanism may hamper the ability of isohydric species to respond to ongoing global change, by aggravating the interactive impacts of stoichiometric imbalance and water stress caused by anthropogenic N deposition and hotter droughts, respectively.
CD109 deficiency induces osteopenia with an osteoporosis‐like phenotype in vivo
Authors: Mii Shinji , Hoshino Akiyoshi , Enomoto Atsushi , Murakumo Yoshiki , Ito Masako , Yamaguchi Akira , Takahashi Masahide
Published: May 2018

Osteoporosis is a global public health problem that is increasing along with an aging population. A major determinant of osteoporosis is high bone turnover, which results from osteoclast activation. CD109 is a glycosylphosphatidylinositol‐anchored glycoprotein, a deficiency that leads to a psoriasis‐like skin inflammation in mice. Although the expression of CD109 has been reported in mouse pre‐osteoclast cells, its function in osteoclasts in vivo remains largely unknown. To investigate the physiological role of CD109 in bone metabolism, we analyzed bones from wild‐type and CD109‐deficient adult mice. Micro‐computed tomography analysis of the femur (thigh bone) showed that bone volume was lower in CD109‐deficient mice than in wild‐type mice. Bone histomorphometric analysis showed not only a reduction in bone volume but also an increase in bone turnover in CD109‐deficient mice as compared with wild‐type mice. Additionally, we measured serum levels of several markers of bone turnover and found a significant increase in the N‐terminal telopeptide of type I collagen, a bone resorption marker, as well as alkaline phosphatase, a bone formation marker, in CD109‐deficient mice. These results indicate that CD109 deficiency induces a high‐turnover, osteoporosis‐like phenotype, which suggests that CD109 plays a role in bone metabolism in vivo.
Conceptions of kingship in high‐medieval Germany in historiographical perspective
Authors: Dale Johanna
Published: May 2018

Historians of medieval kingship have been influenced by a teleology that sees the development of the secular modern state as inevitable. Therefore, the desacralisation of kingship is considered a key moment on the path to modern state formation. In Germany, the moment of desacralisation has traditionally been identified in 1077, when king Henry IV submitted to Pope Gregory VII at Canossa. Thereafter, the spell of Ottonian sacral kingship was punctured, and Henry's twelfth‐century successors were forced to look to Roman law and the support of the princes for legitimation. In this essay, we first examine the historiography of this traditional three‐phase paradigm, before introducing some recent scholarship that challenges the paradigm and criticises the universal explanatory power of the demise of sacral kingship as a catch‐all reason for change, at the expense of complex political, social, and economic factors.
Flying insect abundance declines with increasing road traffic
Authors: Martin Amanda E. , Graham Shannon L. , Henry Melissa , Pervin Erik , Fahrig Lenore
Published: May 2018

One potentially important but underappreciated threat to insects is road mortality. Road kill studies clearly show that insects are killed on roads, leading to the hypothesis that road mortality causes declines in local insect population sizes.

In this study we used custom‐made sticky traps attached to a vehicle to target diurnal flying insects that interact with roads, sampling along 10 high‐traffic and 10 low‐traffic rural roads in southeastern Ontario, Canada. We used a paired sampling design to control for potentially confounding differences in the road characteristics (e.g. road width) and surrounding land covers (e.g. housing density) between high‐traffic and low‐traffic roads. We then used these data to test the prediction that fewer flying insects collide with vehicles, per vehicle (i.e. insect abundance is lower), on high‐traffic than low‐traffic roads.

We found significantly fewer insects at the high‐traffic roads than at the low‐traffic roads as predicted. There was a 23.5% decline in the number of insects/km/vehicle on high‐traffic relative to low‐traffic roads.

Given the high rates of insect mortality observed in previous studies, it is likely that road mortality contributes to these observed negative effects of traffic intensity. Thus the growing global road network is a concern for conservationists and land managers, not only because insect population declines contribute to the ongoing global losses of biodiversity but also because insects play a vital role in food webs and provide important ecosystem services.
Detection of an avian lineage influenza A(H7N2) virus in air and surface samples at a New York City feline quarantine facility
Authors: Blachere Francoise M. , Lindsley William G. , Weber Angela M. , Beezhold Donald H. , Thewlis Robert E. , Mead Kenneth R. , Noti John D.
Published: May 2018

Background

In December 2016, an outbreak of low pathogenicity avian influenza (LPAI) A(H7N2) occurred in cats at a New York City animal shelter and quickly spread to other shelters in New York and Pennsylvania. The A(H7N2) virus also spread to an attending veterinarian. In response, 500 cats were transferred from these shelters to a temporary quarantine facility for continued monitoring and treatment.

Objectives

The objective of this study was to assess the occupational risk of A(H7N2) exposure among emergency response workers at the feline quarantine facility.

Methods

Aerosol and surface samples were collected from inside and outside the isolation zones of the quarantine facility. Samples were screened for A(H7N2) by quantitative RT‐PCR and analyzed in embryonated chicken eggs for infectious virus.

Results

H7N2 virus was detected by RT‐PCR in 28 of 29 aerosol samples collected in the high‐risk isolation (hot) zone with 70.9% on particles with aerodynamic diameters >4 μm, 27.7% in 1‐4 μm, and 1.4% in <1 μm. Seventeen of 22 surface samples from the high‐risk isolation zone were also H7N2 positive with an average M1 copy number of 1.3 × 103. Passage of aerosol and surface samples in eggs confirmed that infectious virus was present throughout the high‐risk zones in the quarantine facility.

Conclusions

By measuring particle size, distribution, and infectivity, our study suggests that the A(H7N2) virus had the potential to spread by airborne transmission and/or direct contact with viral‐laden fomites. These results warranted continued A(H7N2) surveillance and transmission‐based precautions during the treatment and care of infected cats.
Standing on shaky ground and living in the now: How resource amount and stability influence time perspectives
Authors: Gore Jonathan S.
Published: May 2018

Time perspective predicts multiple health, antisocial, and prosocial outcomes, but the factors that explain it are rarely examined. Two studies examined the unique influences of resource amount and stability on time perspective. In both studies, participants (n = 300 college students for Study 1, 167 working adults for Study 2) reported the amount and stability of their income, and their time perspectives. The instability of financial and social resources was associated with present‐fatalistic perspective. The stability of personal resources was associated with future‐planful perspective. Implications for developmental and cognitive theories of risky behavior are discussed.
Blood pressure measurement techniques: Assessing performance in outpatient settings of a tertiary‐level hospital in Rwanda
Authors: Kabakambira Jean Damascene , Niyonsenga Zachee , Hategeka Marthe , Igiraneza Grace , Benurugo Genevieve , Lucero‐Prisno III Don Eliseo , Hategeka Celestin
Published: May 2018

Cardiovascular diseases (CVD) are the leading cause of mortality globally. Hypertension is a known modifiable risk factor for CVD. Diagnosis and management of hypertension hinges upon accurate blood pressure (BP) measurement. In this study, we assessed performance to recommended guidelines for BP measurement in Rwanda. In 2017, a cross‐sectional study investigating performance on 11 techniques recommended for BP measurement was undertaken across outpatient settings of 3 departments at the University Teaching Hospital of Kigali, Rwanda. Performance was checked by an inside observer. The study enrolled 164 patients. The overall mean performance on the 11 BP measurement techniques was 5.69 (±1.02) out of the 11 possible points. There was no significant difference in performance across departments (P = .28). The findings suggest that performance on currently recommended guidelines for BP measurement is not optimal. Going forward, it is important to implement interventions that will enhance performance given that diagnosis and management of hypertension depend upon accurate BP measurement.
Evaluation of the influence of implant placement timing on the esthetic outcomes of single tooth implant treatment in the anterior maxilla: A retrospective study
Authors: Arora Himanshu , Ivanovski Saso
Published: May 2018

Objectives

The purpose of this retrospective study was to investigate the influence of implant placement timing on the esthetic outcomes for single implants in the anterior maxilla.

Materials and methods

One hundred and ten patients (48 males; 62 females) who received a single‐tooth implant after extraction either immediately (Type 1); after 4–8 weeks (Type 2); after 8–16 weeks (Type 3); or more than 16 weeks (Type 4) were evaluated in terms of esthetic outcomes after a mean post‐placement interval of 26.3 months (range 12–116). Esthetic outcomes were measured using the Pink and White Esthetic Score (PES; WES). Stepwise regression analysis was performed to analyze the effect of timing of placement, as well as patient demographics and other clinical parameters on the esthetic outcomes.

Results

No statistically significantly differences in PES were found between the various treatment modalities with Type 1 implants (n = 33) scoring 10.58 ± 1.65 (median: 11), followed by 10.36 ± 2.09 (median: 10.5), 9.68 ± 2.43 (median: 10), and 9.63 ± 2.21 (median: 10) for Type 2 (n = 14), Type 3 (n = 19), and Type 4 (n = 44), respectively. For immediate implants, a trend towards better esthetic outcomes was observed when implant placement was done flaplessly in cases with intact buccal bone (Type 1A, median PES 11) as compared to cases with partial/complete missing buccal plates where a flap was raised (Type 1B, median PES 10). Overall, the only parameter that influenced esthetic outcomes (as measured by PES) was gender, with females having significantly superior results. The median WES was 8 and 96% of the crowns were deemed esthetically acceptable, with crowns placed by specialist prosthodontists yielding higher scores than those placed by general practitioners.

Conclusions

Single tooth implants in the anterior maxilla showed satisfactory outcomes when measured with objective esthetic criteria. Timing of implant placement did not significantly influence the esthetic outcomes, although a trend towards better outcomes was seen with immediate implant placement as observed by higher median PES values.

CLINICAL SIGNIFICANCE

Single tooth implant placement in the anterior maxilla is a predictable treatment modality for achieving acceptable esthetic outcomes regardless of the timing of placement.
Adhesive/silane application effects on bond strength durability to a lithium disilicate ceramic
Authors: Romanini‐Junior Jose C. , Kumagai Rose Y. , Ortega Luiz F. , Rodrigues Jose A. , Cassoni Alessandra , Hirata Ronaldo , Reis Andre F.
Published: May 2018

Objective

To test the effects of different adhesive protocols and silane application on the adhesive durability to a Lithium Disilicate reinforced glass ceramic.

Methods

Forty disks of 13 mm diameter (E.max Press) were used. After etching with 9.5% HF for 20 seconds, disks were randomly assigned into 4 groups according to the adhesive/silane protocol: silane application only (SIL); silane application followed by adhesive (SILXP—XP Bond); silane‐containing adhesive (SBU—ScotchBond Universal); silane application followed by silane‐containing adhesive (SILSBU). Four resin composite cylinders of 1‐mm diameter and 3‐mm height were made on each ceramic disk and tested in shear. Specimens were stored in water for 24 hours or 12 months prior to testing. Results were statistically analyzed by two‐way ANOVA and Tukey test.

Results

After 24 hours, the highest SBS values were observed for SILXP and SILSBU. However, after 12 months, SILXP and SILSBU presented a significant reduction in SBS, while the highest SBS were observed for SIL. For SBU, no significant reduction in SBS was observed, however, it showed the lowest SBS after 12 months.

Conclusions

Regardless of the presence of silane in the composition of SBU, previous silane application is still recommended prior to cementation of Lithium Disilicate.

Clinical Significance

The application of silane as a separate step is recommended prior to cementation of Lithium Disilicate reinforced glass‐ceramic, independent of the presence of silane within the universal adhesive solution.
Accuracy of pan‐European coastal flood mapping
Authors: Paprotny D. , Morales‐Nápoles O. , Vousdoukas M. I. , Jonkman S. N. , Nikulin G.
Published: May 2018

Coastal flood maps covering the whole European continent have become available in recent years. However, their ability to complement or replace high‐resolution local flood maps was not investigated so far. In this paper we compare pan‐European estimates of extreme sea levels and coastal flood extents at given return periods with observations and high‐resolution reference maps. The analysis is done for two pan‐European assessments and one global study. We find that whereas the models have good accuracy in estimating storm surge heights, large disparities exist between the large‐scale flood maps and four local maps of flood extents from England, the Netherlands, Poland, and France. Moreover, the accuracy of the underlying digital elevation model and assumptions about flood protection existing in a given area influence significantly the results. In addition, the first pan‐European projection of temporal trends in the size of flood zones is presented, with and without assuming flood protection levels.
Platinum‐resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine
Authors: Komiyama Shinichi , Kugimiya Tsuyoki , Takeya Chiaki , Takahashi Rena , Kubushiro Kaneyuki
Published: May 2018

Platinum‐resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long‐term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77‐year‐old woman with high‐grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin. In 2014, recurrence was detected again, but CR was achieved by third‐line combination therapy with gemcitabine, carboplatin and bevacizumab. In 2015, the third recurrence was found during bevacizumab maintenance therapy. Fourth‐line treatment was initiated with BEV + GEM, which has maintained stable disease for 29 months. This is the first report about marked prolongation of survival by BEV + GEM in a patient with platinum‐resistant recurrent ovarian cancer.
Cortical Thickness Estimations of FreeSurfer and the CAT12 Toolbox in Patients with Alzheimer's Disease and Healthy Controls
Authors: Seiger Rene , Ganger Sebastian , Kranz Georg S. , Hahn Andreas , Lanzenberger Rupert
Published: May 2018

BACKGROUND AND PURPOSE

Automated cortical thickness (CT) measurements are often used to assess gray matter changes in the healthy and diseased human brain. The FreeSurfer software is frequently applied for this type of analysis. The computational anatomy toolbox (CAT12) for SPM, which offers a fast and easy‐to‐use alternative approach, was recently made available.

METHODS

In this study, we compared region of interest (ROI)‐wise CT estimations of the surface‐based FreeSurfer 6 (FS6) software and the volume‐based CAT12 toolbox for SPM using 44 elderly healthy female control subjects (HC). In addition, these 44 HCs from the cross‐sectional analysis and 34 age‐ and sex‐matched patients with Alzheimer's disease (AD) were used to assess the potential of detecting group differences for each method. Finally, a test‐retest analysis was conducted using 19 HC subjects. All data were taken from the OASIS database and MRI scans were recorded at 1.5 Tesla.

RESULTS

A strong correlation was observed between both methods in terms of ROI mean CT estimates (R2 = .83). However, CAT12 delivered significantly higher CT estimations in 32 of the 34 ROIs, indicating a systematic difference between both approaches. Furthermore, both methods were able to reliably detect atrophic brain areas in AD subjects, with the highest decreases in temporal areas. Finally, FS6 as well as CAT12 showed excellent test‐retest variability scores.

CONCLUSION

Although CT estimations were systematically higher for CAT12, this study provides evidence that this new toolbox delivers accurate and robust CT estimates and can be considered a fast and reliable alternative to FreeSurfer.
Prevalence of subclinical hypothyroidism in obese children or adolescents and association between thyroid hormone and the components of metabolic syndrome
Authors: Jin Hye Young
Published: May 2018

Aim

Subclinical hypothyroidism is defined as elevated thyroid‐stimulating hormone (TSH) levels with the normal concentrations of thyroxine (T4) or free thyroxine (fT4), and its clinical significance is unclear. The purpose of this study is to investigate the prevalence of subclinical hypothyroidism in children and adolescents and determine the relationship between lipid profiles, insulin resistance and thyroid hormones.

Methods

A retrospective, cross‐sectional study was performed using data from a subset of the KNHANES VI. The subjects whose ages were in the range of 10–19 years were enrolled when their thyroid function tests were available (n = 1104), and their laboratory and anthropometric data were analysed.

Results

Subclinical hypothyroidism was more commonly identified in the obese group (27 of 111) compared to the other groups (127 of 993) (24.3 vs. 12.8%, P = 0.002). Total cholesterol and triglyceride levels were higher in a group with subclinical hypothyroidism. Body mass index (BMI) was positively correlated with serum concentrations of the TSH and negatively correlated with serum concentrations of fT4 after adjusting for age. The concentrations of total cholesterol and triglyceride were positively correlated with the TSH concentrations following adjustment for age and BMI standard deviation scores. The fT4 concentrations were negatively linked with total cholesterol after adjusting for age and BMI standard deviation scores. No significant correlation was found between insulin resistance index and TSH and fT4.

Conclusions

Subclinical hypothyroidism was common in the obese group, and the concentrations of TSH were linked with the lipid profile. Subclinical hypothyroidism in obese children or adolescents should be closely monitored while also evaluating metabolic risk factors.
Lotteries and Lindahl prices in public good provision
Authors: Franke Jörg , Leininger Wolfgang
Published: May 2018

Lotteries are traditional instruments for fundraising in general. Morgan has shown that they can also be very effective in the provision of a public good. However, a fair lottery can only enhance provision but never result in the efficient amount. Franke and Leininger show how—by borrowing from optimal contest theory—biased lotteries can provide the efficient amount of the public good. This paper aligns this result with standard public good theory, in particular the classic notion of Lindahl pricing. It shows that biased lotteries can—implicitly—implement Lindahl pricing of the public good in noncooperative Nash equilibrium.
Ineffectiveness of saxagliptin as a neuroprotective drug in 6-OHDA-lesioned rats
Authors: Turnes Joelle de Melo , Bassani Taysa Bervian , Souza Leonardo C , Vital Maria A B F
Published: May 2018

Objectives

To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats.

Methods

Male Wistar rats (weighing 280–300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days. The motor function was evaluated using the open field and rotarod (RT) tests. In addition, cognition was assessed with the novel object recognition test (ORT). After the evaluation of the behavioural tests, the animals were transcardially perfused to perform immunohistochemistry staining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc).

Key findings

Saxagliptin impaired the memory of animals in the sham group.

Conclusions

Saxagliptin treatment did not exhibit neuroprotection and it did not improve the cognitive and motor deficits in the 6-OHDA model of PD. Interestingly, when saxagliptin was administered to the sham animals, a cognitive decline was observed. Therefore, this drug should be investigated as a possible treatment for PTSD.