bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycogen synthase kinase‐3β in patients with bipolar I disorder: results from a prospective study
Authors: Jacoby Anne S , Munkholm Klaus , Vinberg Maj , Joaquim Helena GP , Talib Leda L , Gattaz Wagner F , Kessing Lars V
Published: June 2016

Objectives

The enzyme glycogen synthase kinase‐3β (GSK3β) is involved in the mechanisms of action of lithium and may play a role in relation to affective states in bipolar disorder. The objectives of the present study were to compare the activity of GSK‐3β (measured as levels of phosphorylated GSK‐3β [p‐GSK‐3β]) between patients with bipolar disorder in the euthymic state and healthy control subjects, and to investigate whether GSK‐3β activity varies with affective states in patients with bipolar I disorder.

Methods

In a prospective 6–12‐month follow‐up study, we investigated state‐specific, intraindividual alterations in the activity of GSK‐3β in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic, depressive and manic states and compared this with repeated measurements in healthy control subjects. Data were analyzed using linear mixed‐effects models.

Results

From baseline to the end of follow‐up, blood samples were drawn from the 60 patients during 181 affective states, comprising 60 manic, 11 mixed, 23 depressive, and 87 states of euthymia. A total of 69 blood samples were drawn from 35 healthy control subjects, with two samples from the same subject taken three months apart. In mixed‐model analysis, p‐GSK‐3β was decreased in the euthymic state of subjects with bipolar disorder compared with healthy control subjects (b=0.63, 95% confidence interval [CI]: 0.42–0.96, P=.03). In addition, p‐GSK‐3β varied with affective states, being increased in depressive (b=1.68, 95% CI: 1.08–2.62, P=.02) and mixed (b=2.07, 95% CI: 1.12–3.84, P=.02) states but not in mania compared with euthymia.

Conclusions

The activity of GSK‐3β is altered in euthymic bipolar disorder compared with healthy control subjects and varies with affective states.
The influence of cooperative relations of small businesses on environmental protection intensity
Authors: Benito‐Hernández Sonia , Platero‐Jaime Manuel , Esteban-Sánchez Pablo
Published: June 2016

This study examines the relationship between cooperative business relations in small businesses (fewer than 50 employees) and environmental protection, one of the most important policies of social responsibility in manufacturing. We reviewed the literature and carried out an empirical study of 930 small manufacturing firms in Spain. Results indicate that small businesses that maintain and improve their cooperative relations through business networking with universities, competitors, suppliers and customers spend more on environmental protection. The managerial, practical, research and policy implications of the obtained research findings are discussed.
Longitudinal Positron Emission Tomography in Preventive Alzheimer's Disease Drug Trials, Critical Barriers from Imaging Science Perspective
Authors: Shokouhi Sepideh , Campbell Desmond , Brill Aaron B. , Gwirtsman Harry E. ,   The Alzheimer's Disease Neuroimaging Initiative
Published: June 2016

Recent Alzheimer's trials have recruited cognitively normal people at risk for Alzheimer's dementia. Due to the lack of clinical symptoms in normal population, conventional clinical outcome measures are not suitable for these early trials. While several groups are developing new composite cognitive tests that could serve as potential outcome measures by detecting subtle cognitive changes in normal people, there is a need for longitudinal brain imaging techniques that can correlate with temporal changes in these new tests and provide additional objective measures of neuropathological changes in brain. Positron emission tomography (PET) is a nuclear medicine imaging procedure based on the measurement of annihilation photons after positron emission from radiolabeled molecules that allow tracking of biological processes in body, including the brain. PET is a well‐established in vivo imaging modality in Alzheimer's disease diagnosis and research due to its capability of detecting abnormalities in three major hallmarks of this disease. These include (1) amyloid beta plaques; (2) neurofibrillary tau tangles and (3) decrease in neuronal activity due to loss of nerve cell connection and death. While semiquantitative PET imaging techniques are commonly used to set discrete cut‐points to stratify abnormal levels of amyloid accumulation and neurodegeneration, they are suboptimal for detecting subtle longitudinal changes. In this study, we have identified and discussed four critical barriers in conventional longitudinal PET imaging that may be particularly relevant for early Alzheimer's disease studies. These include within and across subject heterogeneity of AD‐affected brain regions, PET intensity normalization, neuronal compensations in early disease stages and cerebrovascular amyloid deposition.
Direct modulation of TRPM4 and TRPM3 channels by the phospholipase C inhibitor U73122
Authors: Leitner Michael G , Michel Niklas , Behrendt Marc , Dierich Marlen , Dembla Sandeep , Wilke Bettina U , Konrad Maik , Lindner Moritz , Oberwinkler Johannes , Oliver Dominik
Published: June 2016

Background and Purpose

Signalling through phospholipase C (PLC) controls many cellular processes. Much information on the relevance of this important pathway has been derived from pharmacological inhibition of the enzymatic activity of PLC. We found that the most frequently employed PLC inhibitor, U73122, activates endogenous ionic currents in widely used cell lines. Given the extensive use of U73122 in research, we set out to identify these U73122‐sensitive ion channels.

Experimental Approach

We performed detailed biophysical analysis of the U73122‐induced currents in frequently used cell lines.

Key Results

At concentrations required to inhibit PLC, U73122 modulated the activity of transient receptor potential melastatin (TRPM) channels through covalent modification. U73122 was shown to be a potent agonist of ubiquitously expressed TRPM4 channels and activated endogenous TRPM4 channels in CHO cells independently of PLC and of the downstream second messengers PI(4,5)P2 and Ca2+. U73122 also potentiated Ca2+‐dependent TRPM4 currents in human Jurkat T‐cells, endogenous TRPM4 in HEK293T cells and recombinant human TRPM4. In contrast to TRPM4, TRPM3 channels were inhibited whereas the closely related TRPM5 channels were insensitive to U73122, showing that U73122 exhibits high specificity within the TRPM channel family.

Conclusions and Implications

Given the widespread expression of TRPM4 and TRPM3 channels, these actions of U73122 must be considered when interpreting its effects on cell function. U73122 may also be useful for identifying and characterizing TRPM channels in native tissue, thus facilitating the analysis of their physiology.
Effect of pretreatment with antifungal agents on clinical outcomes in fungal keratitis
Authors: Sun Catherine Q , Prajna N Venkatesh , Krishnan Tiruvengada , Rajaraman Revathi , Srinivasan Muthiah , Raghavan Anita , O'Brien Kieran S , McLeod Stephen D , Acharya Nisha R , Rose‐Nussbaumer Jennifer ,   Mycotic Ulcer Treatment Trial Group
Published: June 2016

Background

To determine if pretreatment with antifungal agents is predictive of worse clinical outcome in a fungal keratitis clinical trial.

Design

Non‐pre‐specified subgroup analysis of a randomized controlled trial in a tertiary hospital.

Participants

Three hundred twenty‐three fungal ulcer cases with an enrolment visual acuity of 20/40 to 20/400.

Methods

The Mycotic Ulcer Treatment Trial I was a randomized, double‐masked trial to determine the optimal treatment for filamentous fungal keratitis at the Aravind Eye Care System, India. Enrolled cases were randomized to receive topical natamycin or voriconazole. Prior antifungal medication use, dose and duration were collected at enrolment. A subgroup analysis was performed to determine if patients using natamycin or azoles at presentation have worse clinical outcomes compared with those who were not pretreated.

Main Outcome Measures

Three‐month visual acuity (primary), 3‐month infiltrate or scar size, corneal perforation and/or transplant and re‐epithelialization time.

Results

Of the 323 patients enrolled, 44% presented on an antifungal agent. Pretreated patients had larger mean baseline infiltrate size (P < 0.001) and epithelial defect size (P = 0.02). Multivariate regression analysis demonstrated that pretreatment was associated with significantly worse 3‐month visual acuity (P = 0.006), larger 3‐month scar size (P < 0.001) and increased odds of corneal perforation and/or transplant (P = 0.001).

Conclusions

Fungal keratitis that is smear‐positive despite being pretreated with appropriate antifungal agents appears to be a risk factor for worse outcomes, likely a result of initial ulcer severity and treatment failure. These patients may benefit from more aggressive multimodal therapy at a tertiary centre.
EF1A1/HSC70 Cooperatively Suppress Brain Endothelial Cell Apoptosis via Regulating JNK Activity
Authors: Liu Ying , Jiang Shu , Yang Peng‐Yuan , Zhang Yue‐Fan , Li Tie‐Jun , Rui Yao‐Cheng
Published: June 2016

Aims

In our previous study, eEF1A1 was identified to be a new target for protecting brain ischemia injury, but the mechanism remains largely unknown. In this study, we screened the downstream cellular protein molecules interacted with eEF1A1 and found mechanism of eEF1A1 in brain ischemia protection.

Methods and results

Through co‐immunoprecipitation and mass spectrometry for searching the interaction of proteins with eEF1A1 in bEnd3 cells, HSC70 was identified to be a binding protein of eEF1A1, which was further validated by Western blot and immunofluorescence. eEF1A1 or HSC70 knockdown, respectively, increased OGD‐induced apoptosis of brain vascular endothelial cells, which was detected by Annexin V‐FITC/PI staining. HSC70 or eEF1A1 knockdown enhances phosphorylated JNK, phosphorylation of c‐JUN (Ser63, Ser73), cleaved caspase‐9, and cleaved caspase‐3 expression, which could be rescued by JNK inhibitor.

Conclusion

In summary, our data suggest that the presence of chaperone forms of interaction between eEF1A1 and HSC70 in brain vascular endothelial cells, eEF1A1 and HSC70 can play a protective role in the process of ischemic stroke by inhibiting the JNK signaling pathway activation.
A systematic review of presacral extramedullary haematopoiesis: a diagnosis to be considered for presacral masses
Authors: Zhou P. P. , Clark E. , Kapadia M. R.
Published: June 2016

Aim

Presacral masses are uncommon and have malignant potential; treatment typically includes surgical excision. However, there are conditions such as extramedullary haematopoiesis (EMH) which are benign. The present study aimed to summarize the presentation of presacral EMH in our institution, to review the literature and to offer management strategies for this rare condition.

Method

The literature was searched for articles related to presacral EMH, and case reports were collected from articles meeting the inclusion criteria. We collected data on patient demographics, diagnostic investigation, management and the results of treatment.

Results

Thirty‐nine patients were included in the systematic review. Initial imaging included computed tomography (CT), magnetic resonance imaging (MRI) or ultrasound (US) suggestive of EMH. Some patients then underwent a technetium scan (n = 7, 18%), biopsy of the presacral lesion (n = 27, 69%) or excision of the entire mass (n = 3, 8%). All patients who underwent technetium scan were confirmed to have EMH, demonstrating enhancement similar to bone marrow. Patients who underwent technetium scan and presacral mass biopsy had concordant results confirming presacral EMH (n = 5, 13%). Data on management were available for 35/39 (90%) with most patients followed by clinical observation (n = 20, 51%). Symptomatic patients were treated with radiotherapy (15%), surgical excision (15%) or hydroxyurea (5%) and blood transfusions (10%). Most (81%, n = 17/21) patients whose outcome was reported remained asymptomatic or experienced pain relief.

Conclusion

Although uncommon, EMH should be considered in the differential diagnosis of a presacral mass. Presacral EMH is a benign condition that can be suspected on CT or MRI and confirmed with technetium scan. Patients may not necessarily need to undergo biopsy to confirm haematopoietic elements. Unlike other presacral masses, patients diagnosed with presacral EMH can be managed by observation. If symptomatic, radiotherapy or surgical excision may be offered.
Meta‐analysis and systematic review of procalcitonin‐guided treatment in acute exacerbation of chronic obstructive pulmonary disease
Authors: Lin Changyang , Pang Qiyuan
Published: June 2016

Introduction

To evaluate the method of procalcitonin (PCT)‐guided treatment on antibiotics in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

Database including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trails were searched to find relevant trails. Randomized and quasi‐randomized trials of PCT‐guided treatment in adult patients with AECOPD were included. Effects on primary outcome (i.e., antibiotic prescriptions, mortality, and clinical success) were accessed in this meta‐analysis.

Results

Four trials involving 679 patients were included. PCT‐guided treatment significantly reduced antibiotic use (OR 0.26, 95% CI 0.14–0.50, P < 0.0001) in comparison to standard treatment, without increasing clinical failure (OR 1.10, 95% CI 0.70–1.74, P = 0.68; I2 = 0%) and mortality (OR 0.86, 95% CI 0.44–1.68, P = 0.66). The rate of readmission and exacerbation at follow‐up period was similar in both groups.

Conclusion

Results from this meta‐analysis suggest PCT‐guided treatment can safely reduce antibiotic overuse in patients with AECOPD.
Oki stent application in different indications: Six cases
Authors: Özgül Mehmet Akif , Çetinkaya Erdoğan , Çörtük Mustafa , Tanrıverdi Elif , Yıldırım Binnaz Zeynep , Balci Merih Kalamanoğlu , Issaka Adamu , Özgül Güler
Published: June 2016

Introduction

We have used Oki stents for a number of different indications. After discovering that there are limited reports in the literature on these stents, we were motivated to share our experiences in Oki stenting.

Objectives

While there is vast knowledge on double Y‐stents, the Oki stent is a relatively recent development in pulmonology. Here, we demonstrate that stenting of the right secondary carina using an Oki stent should be considered for obstructions in this region.

Methods

We placed 13 mm × 10 mm × 9 mm Oki stents in six patients under general anesthesia via rigid bronchoscopy.

Results

Three cases were post‐transplant patients with malacia, stenosis, and bronchopleural fistula. One case had an airway obstruction due to malignant disease, another case had a right aortic arc and aberrant left subclavian artery anomaly, and the final case had bronchopleural fistula. No serious complications were observed during stent placement.

Conclusions

Oki stents can safely be used for many clinical conditions. Patients benefit greatly from stenting; however, two of our cases died due to infection, and one case died due to malignancy.
Substance use disorders comorbid with mood and anxiety disorders in the Australian general population
Authors: Prior Katrina , Mills Katherine , Ross Joanne , Teesson Maree
Published: June 2016

Introduction and Aims

Substance use disorders (SUDs) are common and frequently co‐occur with mood and anxiety disorders. This paper provides a detailed analysis of patterns, prevalence and correlates of mood and anxiety disorders among those with a (i) pure SUD; (ii) SUD plus a mood or anxiety disorder (SUDs + 1); and (iii) SUD plus a mood and anxiety disorder (SUDs + 2).

Design and Methods

Data came from the 2007 National Survey of Mental Health and Wellbeing; a nationally representative household survey of 8841 Australians aged 16–85 years.

Results

The 12‐month prevalence of SUDs was 5.1%. Of those with a 12‐month SUD, 65% met the criteria for pure SUDs, 19% for SUDs + 1 and 16% for SUDs + 2. Major depression was the most common mood disorder in both comorbid groups. One‐third of SUDs + 1 experienced social phobia, while over half of SUDs + 2 experienced generalised anxiety disorder. Compared with pure SUDs, SUDs + 1 experienced two times more and SUDs + 2 experienced over four times more days out of role in the preceding 30 days. Both comorbid groups were more likely to experience severe levels of impairment. SUDs + 2 were over 18 times more likely to experience suicidal thoughts in the same year. SUDs + 1 were over three times and SUDs + 2 were over 10 times more likely to have had one or more consultations with a health professional in the previous year.

Discussions and Conclusions

These findings highlight the complexities inherent with responding to and treating multiple comorbidities among substance users and emphasise the need for coordinated, cohesive responses from drug and alcohol treatment services.[Prior K, Mills K, Ross J, Teesson M. Substance use disorders comorbid with mood and anxiety disorders in the Australian general population. Drug Alcohol Rev 2017;36:317–324]
MRIclassification system (MRICS) for children with cerebral palsy: development, reliability, and recommendations
Authors: Himmelmann Kate , Horber Veronka , De La Cruz Javier , Horridge Karen , Mejaski‐Bosnjak Vlatka , Hollody Katalin , Krägeloh‐Mann Ingeborg ,   the SCPE Working Group
Published: June 2016

Aim

To develop and evaluate a classification system for magnetic resonance imaging (MRI) findings of children with cerebral palsy (CP) that can be used inCPregisters.

Method

The classification system was based on pathogenic patterns occurring in different periods of brain development. TheMRIclassification system (MRICS) consists of five main groups: maldevelopments, predominant white matter injury, predominant grey matter injury, miscellaneous, and normal findings. A detailed manual for the descriptions of these patterns was developed, including test cases (http://scpe.edu.eacd.org/scpe/reference-and-training-manual/rtm.php). A literature review was performed andMRICSwas compared with other classification systems. An exercise was carried out to check applicability and interrater reliability. Professionals working with children withCPor inCPregisters were invited to participate in the exercise and chose to classify either 18MRIs orMRIreports of children withCP.

Results

Classification systems in the literature were compatible withMRICSand harmonization possible. Interrater reliability was found to be good overall (k=0.69; 0.54–0.82) among the 41 participants and very good (k=0.81; 0.74–0.92) using the classification based on imaging reports.

Interpretation

Surveillance of Cerebral Palsy in Europe (SCPE) proposes theMRICSas a reliable tool. Together with its manual it is simple to apply forCPregisters.
International Technology Spillovers and Growth over the Past 142 Years: The Role of Genetic Proximity
Authors: Madsen Jakob B. , Farhadi Minoo
Published: June 2016

This paper suggests genetic proximity, in addition to geographic proximity and imports, as a factor facilitating international knowledge transmission, where knowledge is measured as the stock of knowledge as well as research intensity to allow for the possibility that international knowledge spillovers have permanent productivity growth effects. Using data for 31 countries with diverse development paths over the period 1870–2011, the results show that genetic proximity and imports are important in facilitating knowledge transmission, and that knowledge spillovers have permanent growth effects.
Virulence of Bursaphelenchus mucronatus to pine seedlings and trees under field cownditions
Authors: Zhou L. F. , Chen F. M. , Wang J. C. , Pan H. Y. , Ye J. R.
Published: June 2016

Bursaphelenchus mucronatus is a parasitic nematode of pine that is widely distributed in the natural pine forests of Asia and Europe. It has a very similar morphology and biology to that of Bursaphelenchus xylophilus, the causal agent of pine wilt disease, but has generally been considered to be non‐pathogenic to pine. However, in some provinces of China, B. mucronatus has been isolated from dead pine trees rather than B. xylophilus. Previous studies have shown that B. mucronatus can induce the death of pine seedlings under glasshouse conditions. To investigate the virulence of B. mucronatus, 2‐year‐old seedlings of Pinus massoniana and Pinus elliottii were inoculated with one of six isolates of B. mucronatus under field conditions in April 2014 and their condition was monitored over a year. The virulence of the six B. mucronatus isolates differed on the three host species: P. elliottii seedling mortality ranged from zero to six of the 18 inoculated seedlings, whereas P. massoniana seedling mortality ranged from four to 12 of the 18 inoculated seedlings. Three B. mucronatus isolates that appeared to cause different levels of mortality among the seedlings were used to inoculate 12‐year‐old Pinus thunbergii trees in August 2014. The trees were monitored for a year, during which time between 4 and 12 of the 18 inoculated trees in each treatment wilted and died. The average monthly temperature during the test period appeared to be similar to that of the historical average in the test areas; however, both study sites experienced above‐average rainfall. This study demonstrated that B. mucronatus has potential virulence on pine trees and provided experimental evidence that high temperatures or drought stress is not essential for the virulence of B. mucronatus.
Growth rate evolution in improved environments under Prodigal Son dynamics
Authors: Collins Sinéad
Published: June 2016

I use an individual‐based model to investigate the evolution of cell division rates in asexual populations under chronic environmental enrichment. I show that maintaining increased growth rates over hundreds of generations following environmental improvement can be limited by increases in cellular damage associated with more rapid reproduction. In the absence of further evolution to either increase damage tolerance or decrease the cost of repair or rate of damage, environmental improvement does not reliably lead to long‐term increases in reproductive rate in microbes. Here, more rapid cell division rates also increases damage, leading to selection for damage avoidance or repair, and a subsequent decrease in population growth, which I call Prodigal Son dynamics, because the consequences of ‘living fast’ force a return to ancestral growth rates. Understanding the conditions under which environmental enrichment is expected to sustainably increase cell division rates is important in applications that require rapid cell division (e.g. biofuel reactors) or seek to avoid the emergence of rapid cell division rates (controlling biofouling).
Comprehensive characterization of ligand‐induced plasticity changes in a dimeric enzyme
Authors: Baettig Oliver M. , Shi Kun , Yachnin Brahm J. , Burk David L. , Berghuis Albert M.
Published: June 2016

An enzyme's inherent structural plasticity is frequently associated with substrate binding, yet detailed structural characterization of flexible proteins remains challenging. This study employs complementary biophysical methods to characterize the partially unfolded structure of substrate‐free AAC(6′)‐Ii, an N‐acetyltransferase of the GCN5‐related N‐acetyltransferase (GNAT) superfamily implicated in conferring broad‐spectrum aminoglycoside resistance on Enterococcus faecium. The X‐ray crystal structure of AAC(6′)‐Ii is analyzed to identify relative motions of the structural elements that constitute the dimeric enzyme. Comparison with the previously elucidated crystal structure of AAC(6′)‐Ii with acetyl coenzyme A (AcCoA) reveals conformational changes that occur upon substrate binding. Our understanding of the enzyme's structural plasticity is further refined with small‐angle X‐ray scattering and circular dichroism analyses, which together reveal how flexible structural elements impact dimerization and substrate binding. These results clarify the extent of unfolding that AAC(6′)‐Ii undergoes in the absence of AcCoA and provide a structural connection to previously observed allosteric cooperativity of this enzyme.

Database

Structural data are available in the PDB database under the accession number 5E96.
First documented pest outbreak of the herbivorous springtailSminthurus viridis(Collembola) in Europe
Authors: Crotty F. V. , Fychan R. , Benefer C. M. , Allen D. , Shaw P. , Marley C. L.
Published: June 2016

Sminthurus viridis(Collembola: Sminthuridae) is a native of grasslands across Europe and feeds preferentially on clover (Trifoliumspp.) and lucerne (Medicago sativa), although its abundance does not normally reach damaging pest levels (as occurs in Australasia). This research note describes the first quantitative assessment of a pest outbreak of this springtail in Europe, which occurred within an existing experiment investigating the effects of cultivation practices on forage establishment. Using sticky traps to assess the incidence ofS. viridis,we found a significant outbreak consisting of catches that were 10‐fold greater than background levels in nearby undamaged fields. Within the experimental area, lucerne established by direct drilling with herbicide had the highest incidence (105 (± 4·9) individuals per trap) compared to other treatments [79 (± 3·9)]. Results are discussed in terms of how cultivation practice may have imbalanced the ecosystem; for example, herbicide use may have diminished potential refugia for predators during forage establishment. This paper highlights the potential of a currently innocuous, widely established invertebrate to become present at damaging levels in agricultural crops.
Efficacy and safety of pegylated full‐length recombinant factor VIII with extended half‐life for perioperative haemostasis in haemophilia A patients
Authors: Brand B. , Gruppo R. , Wynn T. T. , Griskevicius L. , Lopez Fernandez M. F. , Chapman M. , Dvorak T. , Pavlova B. G. , Abbuehl B. E.
Published: June 2016

Introduction

BAX 855 is a pegylated full‐length recombinant factor VIII (rFVIII) with an extended half‐life, built on a licensed rFVIII (ADVATE®). BAX 855 demonstrated efficacy and safety in prophylaxis and the treatment of bleeding episodes in previously treated patients (PTPs) with severe haemophilia A.

Aim

This phase 3 surgery study evaluates the haemostatic efficacy and safety of BAX 855 for perioperative haemostasis in PTPs with severe haemophilia A undergoing surgery.

Methods

Elective procedures were prospectively classified as major or minor. The dose and frequency of BAX 855 administered perioperatively were to be guided by each patient's pharmacokinetic profile for major procedures or BAX 855 incremental recovery for minor procedures. Haemostatic efficacy was evaluated using a predefined scale. Blood loss was compared to the expected average and maximum blood loss predicted preoperatively.

Results

A total of 15 male patients (aged 19–52 years) underwent 15 procedures (11 major and four minor). The overall intra‐ and perioperative haemostatic efficacy of BAX 855 was ‘excellent’ in all 15 subjects (100%). Postoperatively, evaluated at postoperative Day 1, all treatments were ‘excellent’ except for one minor (dental) procedure which was rated ‘good’. No related adverse events, allergic reactions, thrombotic events, nor signs of immunogenicity in terms of induction of binding antibodies to FVIII, PEG or PEG‐VIII, or FVIII inhibitors were observed.

Conclusion

These results demonstrate that BAX 855 is safe and haemostatically effective in patients with severe haemophilia A undergoing surgery.
Volkmann's ischemic contracture: An unusual complication of arterio‐venous fistula
Authors: Jaryal Ajay , Vikrant Sanjay , Thakur Preyander
Published: June 2016

Native arterio‐venous fistulae (AVF) are vascular access of first choice for chronic hemodialysis. However, AVF are also associated with many adverse events like: primary or secondary failure, infection, lymphedema, stenosis, thrombosis, and ischemia of distal extremities. The most common ischemia related complications of AVF are: ischemic neuropathy and steal syndrome with its consequences like pain and peripheral necrosis. Ischemic muscle contracture is a rare complication of AVF. Herein, we are reporting a case of Volkmann's ischemic contracture developing after creation of brachiocephalic AVF.
“It is amazing how complete is the delusion that beauty is goodness”: expectancies associated with tween makeup ownership
Authors: Thyne Maree , Robertson Kirsten , Thomas Tabitha , Ingram Mikaela
Published: June 2016

Marketing messages socialize individuals into believing that (amongst other practices) consuming cosmetics is the key to beauty and such messages are now being targeted directly to pre‐adolescents. Research shows marketing portrayals of beauty ideals are associated with body disillusionment; however, there is a lack of knowledge on how 'tweens’ enculturation of the necessity to consume beauty products influences their personal development and perspectives of others. The present study examines tweens perceptions of girls who own makeup; 111 girls between 6 and 12 years drew and described a child who owned makeup and a child who did not own makeup, resulting in 222 drawings. The drawings and descriptive words were coded inductively using emerging themes and differences between the two drawings were analysed using SPSS and chi‐square analysis. Findings revealed girls who owned makeup were perceived to be more attractive, happy, and popular than girls who did not wear makeup, however, they were also perceived to be “nastier” than girls who did not own makeup. The findings revealed tweens are enculturated into contemporary beauty ideals and hold strong stereotypes regarding owning makeup. Interpreted through the lens of sociocultural theory and the Halo Effect, findings are discussed in terms of how such ideals shape tweens expectations of others and ultimately may shape their own personal behaviour with regards to social interactions, roles and activities engaged in. We argue that the beauty ideal stereotypes associated with tween cosmetic ownership may be in reality, less than ideal.
Anti‐acetylcholinesterase, antidiabetic, anti‐inflammatory, antityrosinase and antixanthine oxidase activities of Moroccan propolis
Authors: El‐Guendouz Soukaina , Aazza Smail , Lyoussi Badiaâ , Antunes Maria D. , Faleiro Maria L. , Miguel Maria G.
Published: June 2016

Biological properties of Moroccan propolis have been scarcely studied. In the present work, the total phenols and flavonoids from 21 samples of propolis collected in different places of Morocco or 3 supplied in the market were determined, as well as the in vitro capacity for inhibiting the activities of acetylcholinesterase, α‐glucosidase, α‐amylase, lipoxygenase, tyrosinase, xanthine oxidase and hyaluronidase. The results showed that samples 1 (region Fez‐Boulemane, Sefrou city) (IC50 = 0.065, 0.006, 0.020, 0.050, 0.014 mg mL−1) and 23 (marketed) (IC50 = 0.018, 0.002, 0.046, 0.037, 0.008 mg mL−1) had the best in vitro capacity for inhibiting the α‐amylase, α‐glucosidase, lipoxygenase, tyrosinase and xanthine oxidase activities, respectively. A negative correlation between IC50 values and concentration of phenols, flavones and flavanones was found. These activities corresponded to the generally higher amounts of phenols and flavonoids. In the same region, propolis samples have dissimilar phenol content and enzyme inhibitory activities.
How do community pharmacists conceptualise and operationalise self-care support of long-term conditions (LTCs)? An English cross-sectional survey
Authors: Ogunbayo Oladapo J , Schafheutle Ellen I , Cutts Christopher , Noyce Peter R
Published: June 2016

Objectives

To explore community pharmacists' contributions to self-care support of long-term conditions by; investigating their conceptual understanding of self-care principles; identifying self-care support activities they considered important and their engagement in them; and examining barriers and enablers.

Methods

A questionnaire was developed using existing literature and qualitative interviews, piloted and distributed online to a random sample of 10 000 community pharmacists in England between August and November 2014. The questionnaire contained sections addressing the above objectives. Data were analysed using descriptive statistics; free text comments were analysed using content analysis.

Key findings

A total of 609 responses were received; 334 completed all sections of the survey. Responses to statements exploring conceptual understanding showed that respondents were more likely to agree with self-care principles about patients taking responsibility and being more actively involved in their health and care; they agreed less with self-care principles promoting patient autonomy and independence. Respondents considered medicines-related self-care support activities as a lead role for community pharmacy, which they said they engaged in regularly. Whilst many agreed that other self-care support activities such as supporting self-monitoring and collaborative care planning were important, they indicated only limited engagement. Respondents identified access to patient records and availability of private consultation rooms as their main barriers and enablers, respectively; working relationship with GPs and skill-mix in community pharmacy were viewed as both barriers and enablers.

Conclusions

Community pharmacists in this study conceptualised and operationalised self-care support of long-term conditions (LTCs) from a narrow, medicines-focussed perspective, rather than from a multifaceted, patient-focussed perspective. A concerted and coherent strategy that builds on the strengths, and tackles the identified barriers is needed if community pharmacy is to improve contributions to self-care support of LTCs.
Regulating for decent work experience: Meeting the challenge of the rise of the intern
Authors: OWENS Rosemary , STEWART Andrew
Published: June 2016

An important (if under‐researched) feature of modern labour markets has been the growth of unpaid “internships” and other forms of “work experience”. These arrangements may reflect an understandable desire by jobseekers to gain a foothold in highly competitive job markets. But they can open up the possibility of exploitation, as businesses and non‐profit organizations replace what might previously have been paid entry‐level jobs, and may reduce social mobility. Reviewing the legal and policy responses of selected developed countries, the authors seek to lay the foundation for a more effective response to what has become a clear challenge to the objective of securing decent work.
High‐density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation
Authors: Thacker Seth G. , Zarzour Abdalrahman , Chen Ye , Alcicek Mustafa S. , Freeman Lita A. , Sviridov Dennis O. , Demosky Stephen J. , Remaley Alan T.
Published: June 2016

Interleukin‐1β (IL‐1β), a potent pro‐inflammatory cytokine, has been implicated in many diseases, including atherosclerosis. Activation of IL‐1β is controlled by a multi‐protein complex, the inflammasome. The exact initiating event in atherosclerosis is unknown, but recent work has demonstrated that cholesterol crystals (CC) may promote atherosclerosis development by activation of the inflammasome. High‐density lipoprotein (HDL) has consistently been shown to be anti‐atherogenic and to have anti‐inflammatory effects, but its mechanism of action is unclear. We demonstrate here that HDL is able to suppress IL‐1β secretion in response to cholesterol crystals in THP‐1 cells and in human‐monocyte‐derived macrophages. HDL is able to blunt inflammatory monocyte cell recruitment in vivo following intraperitoneal CC injection in mice. HDL appears to modulate inflammasome activation in several ways. It reduces the loss of lysosomal membrane integrity following the phagocytosis of CC, but the major mechanism for the suppression of inflammasome activation by HDL is decreased expression of pro‐IL‐1β and NLRP3, and reducing caspase‐1 activation. In summary, we have described a novel anti‐inflammatory effect of HDL, namely its ability to suppress inflammasome activation by CC by modulating the expression of several key components of the inflammasome.
Exposing information sharing as strategic behavior: power as responsibility and “Trust” buttons
Authors: Bălău Nicoleta , Utz Sonja
Published: June 2016

Online platforms' success depends on individual's information sharing (IS). However, previous research showed that “knowledge is power” is a default‐perception in organizations and that individuals share relatively unimportant information while keeping the important private information for themselves. Trust has also been identified as important enabler of IS. We examined the role of power construed as responsibility for others' outcomes and of a “Trust” button, a theory‐inspired technological feature, using a 2(Power construals: opportunity vs. responsibility) × 2(Buttons: “Like” vs. “Like‐or‐Trust”) × 2(Information sharedness as within‐subjects factor; public, private) design. Findings showed that construing power as responsibility and “Trust” button's presence increased the sharing of private information; clicking behavior yielded insights into the underlying mechanisms. Theoretical and practical implications are discussed.
Enhancing interest in science: exemplars as cues to communal affordances of science
Authors: Clark Emily K. , Fuesting Melissa A. , Diekman Amanda B.
Published: June 2016

A deterrent to recruiting students into STEM pathways is the stereotype that STEM fields do not afford communal goals to work with or help others. We investigate the challenges to cueing communal opportunities in science via brief exposure to scientist exemplars. Both male and female scientists depicted as engaged in communal work increased beliefs that science afforded communal goals and positivity toward science careers (Study 1). Without the direct performance of communal activities, communal affordances were cued only when a female scientist was prototypic of her gender category and respondents were highly communally oriented (Study 2). To change stereotypes that science does not involve communal goals, both female and male scientists can highlight communal aspects of their work.
Clinical efficacy of coronally advanced flap with or without connective tissue graft for the treatment of multiple adjacent gingival recessions in the aesthetic area: a randomized controlled clinical trial
Authors: Cairo Francesco , Cortellini Pierpaolo , Pilloni Andrea , Nieri Michele , Cincinelli Sandro , Amunni Franco , Pagavino Gabriella , Tonetti Maurizio S.
Published: June 2016

Background

The aim of this study was to assess the clinical efficacy of coronally advanced flap (CAF) with or without connective tissue graft (CTG) for the treatment of multiple adjacent gingival recessions in the upper arch.

Material and Methods

Thirty‐two patients with a total of 74 gingival recessions were randomly allocated to the two groups. Outcome measures, collected by a blind examiner, included complete root coverage (CRC), recession reduction (RecRed), keratinized tissue (KT) gain, increase in gingival thickness (GT), patient satisfaction and root coverage esthetic score (RES).

Results

An interaction between treatment and baseline GT was detected. At 1 year, CAF + CTG resulted in better outcomes in terms of CRC (p = 0.0016) and RecRed (p < 0.0001) than CAF alone at sites with thin gingiva (thickness ≤ 0.8 mm). No difference was found between CAF alone and CAF + CTG at sites with thick gingiva (>0.8 mm). CAF resulted in higher aesthetic scores (RES) than CAF + CTG at sites with thick gingiva. CAF + CTG was associated with greater KT gain (p < 0.0001) and greater post‐operative morbidity (p < 0.0001).

Conclusion

Connective tissue graft under CAF results in increased probability of CRC only at sites with thin baseline gingiva. CAF alone is associated with similar clinical outcomes and better aesthetics at sites with thick baseline gingiva.
Neovahlkampfia nana n. sp. Reinforcing an Underrepresented Subclade of Tetramitia, Heterolobosea
Authors: Tyml Tomáš , Lares‐Jiménez Luis F. , Kostka Martin , Dyková Iva
Published: June 2016

The study provides robust genetic evidence that a newly isolated naked ameba with morphological and ultrastructural features indicative of Heterolobosea is a new species. Neovahlkampfia nana n. sp. associates with the yet underrepresented subclade of Tetramitia I. Considerable differences found in 18S rRNA gene sequences of individual molecular clones derived from DNA of five clonal cultures, using a low fidelity DNA polymerase, raised the issue of intragenomic sequence variation, a phenomenon that has not been previously studied in Heterolobosea. However, as proved using a higher fidelity DNA polymerase, the sequence variability observed was introduced by PCR mediated by the low fidelity polymerase and fixed by molecular cloning. This points to the potentially dubious validity of some current nominal species of Heterolobosea that differ from one another in just one or two base positions.
Predator recognition learning in rainbow dartersEtheostoma caeruleum: specific learning and neophobia
Authors: Abudayah W. H. , Mathis A.
Published: June 2016

This study investigated whether rainbow dartersEtheostoma caeruleumcan learn to recognize unfamiliar predators through the process of classical conditioning.Etheostoma caeruleumwere conditioned by exposing them simultaneously to their chemical alarm cues (a known fright stimulus) and either chemical cues from larval ringed salamandersAmbystoma annulatum(unfamiliar predator) or to a blank water cue (control). Conditioning could result in either specific learning of theA. annulatumcue or increased wariness in response to any novel cue (neophobia). To distinguish between these possibilities,E. caeruleumin both groups were exposed to eitherA. annulatumcues alone or to chemical cues from western rat snakesPantherophis obsoletus(novel cue) 2 days after conditioning. Treatment (A. annulatum‐conditioned)E. caeruleum,but not controlE. caeruleum, showed a fright response when they were exposed to both the conditioned (A. annulatum) and novel (P. obsoletus) cues, indicating increased sensitivity to new stimuli. WhenE. caeruleumwere retested after an additional 32 days, however, the fright response occurred only following exposure to the conditioned (A. annulatum) stimulus, indicating that specific learning of theA. annulatumcue had been retained whereas the neophobia to novel stimuli was temporary.
Utilization of 3D printing for an intravital microscopy platform to study the intestinal microcirculation
Authors: BURKOVSKIY I. , LEHMANN C. , JIANG C. , ZHOU J.
Published: June 2016

Intravital microscopy of the intestine is a sophisticated technique that allows qualitative and quantitative in vivo observation of dynamic cellular interactions and blood flow at a high resolution. Physiological conditions of the animal and in particular of the observed organ, such as temperature and moisture are crucial for intravital imaging. Often, the microscopy stage with the animal or the organ of interest imposes limitations on how well the animal can be maintained. In addition, the access for additional oxygen supply or drug administration during the procedure is rather restricted. To address these limitations, we developed a novel intravital microscopy platform, allowing us to have improved access to the animal during the intravital microscopy procedure, as well as improved microenvironmental maintenance. The production process of this prototype platform is based on 3D printing of device parts in a single‐step process. The simplicity of production and the advantages of this versatile and customizable design are shown and discussed in this paper. Our design potentially represents a major step forward in facilitating intestinal intravital imaging using fluorescent microscopy.
Activity and circadian rhythm influence synaptic Shank3 protein levels in mice
Authors: Sarowar Tasnuva , Chhabra Resham , Vilella Antonietta , Boeckers Tobias M. , Zoli Michele , Grabrucker Andreas M.
Published: June 2016

Various recent studies revealed that the proteins of the Shank family act as major scaffold organizing elements in the post‐synaptic density of excitatory synapses and that their expression level is able to influence synapse formation, maturation and ultimately brain plasticity. An imbalance in Shank3 protein levels has been associated with a variety of neuropsychological and neurodegenerative disorders including autism spectrum disorders and Phelan–McDermid syndrome. Given that sleep disorders and low melatonin levels are frequently observed in autism spectrum disorders, and that circadian rhythms may be able to modulate Shank3 signaling and thereby synaptic function, here, we performed in vivo studies on CBA mice using protein biochemistry to investigate the synaptic expression levels of Shank3α during the day in different brain regions. Our results show that synaptic Shank3 protein concentrations exhibit minor oscillations during the day in hippocampal and striatal brain regions that correlate with changes in serum melatonin levels. Furthermore, as circadian rhythms are tightly connected to activity levels in mice, we increased physical activity using running wheels. The expression of Shank3α increases rapidly by induced activity in thalamus and cortex, but decreases in striatum, superimposing the circadian rhythms of different brain regions. We conclude that synaptic Shank3 proteins build highly dynamic platforms that are modulated by the light:dark cycles but even more so driven by activity.

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Using wild‐type CBA mice, we show that Shank3 is a highly dynamic and activity‐regulated protein at synapses. In the hippocampus, changes in synaptic Shank3 levels are influenced by circadian rhythm/melatonin concentration, while running activity increases and decreases levels of Shank3 in the cortex and striatum respectively.
Subanesthetic doses of ketamine stabilize the fusion pore in a narrow flickering state in astrocytes
Authors: Lasič Eva , Rituper Boštjan , Jorgačevski Jernej , Kreft Marko , Stenovec Matjaž , Zorec Robert
Published: June 2016

Ketamine is an anesthetic that exhibits analgesic, psychotomimetic, and rapid antidepressant effects that are of particular neuropharmacological interest. Recent studies revealed astrocytic Ca2+ signaling and regulated exocytosis as ketamine‐targeted processes. Thus high‐resolution cell‐attached membrane capacitance measurements were performed to examine the influence of ketamine on individual vesicle interactions with the plasma membrane in cultured rat astrocytes. Ketamine evoked long‐lasting bursts of repetitive opening and closing of the fusion pore that were both time‐ and concentration‐dependent. Moreover, acute application and subanesthetic doses of ketamine elicited a significant increase in the occurrence of bursts that were characterized by a decreased fusion pore conductance, indicating that the fusion pore was stabilized in a narrow configuration. The time‐ and concentration‐dependent increase in burst occurrence was correlated with a decrease in full fission events. This study has demonstrated a novel effect of ketamine manifested as stabilization of a fusion pore incapable of transiting to full vesicle fission, suggestive of an inhibitory effect on vesicle retrieval. This until now unrecognized effect of ketamine on the vesicle fusion pore might play a role in astroglial release and (re)uptake of molecules, modulating synaptic activity.

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This study demonstrates a novel effect of ketamine on the fusion pore. High‐resolution cell‐attached membrane capacitance measurements revealed that ketamine evokes long‐lasting flickering of a narrow fusion pore that is incapable of transiting to full fission. Astrocytic vesicle fusion/retrieval modified by subanesthetic ketamine doses most likely affects gliotransmission and indicates a non‐neuronal mechanism of ketamine action that may contribute to its behavioral effects.