bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of care of superficial soft tissue sarcomas: it is not always just a lump
Authors: Tan Mark Ting Le , Thompson Stephen R. , Schipp Diane , Bae Susie , Crowe Philip J.
Published: January 2018

Aim

Superficial soft tissue sarcomas (S‐STS) are generally considered low‐risk tumors and have an excellent prognosis when treated with appropriate surgery and adjuvant therapy. However, they are often misdiagnosed then mistreated, leading to significant morbidity. This study aims to examine the patterns of care and outcomes of patients with S‐STS, comparing those initially managed through sarcoma units versus elsewhere.

Methods

Patients with S‐STS from Prince of Wales Hospital in NSW (1995–2013) and Peter MacCallum Cancer Centre in Victoria (2009–2013) were identified from a national sarcoma database. Baseline variables, treatment and disease outcomes were recorded. Statistical tests performed included univariate and multivariate analyses, chi‐square tests, as well as the Kaplan–Meier method for 5‐year local recurrence and survival rates.

Results

Eighty‐nine patients were identified, with 35% initially managed at a sarcoma unit and 65% elsewhere. Patients initially managed at sarcoma units had larger tumors (>5 cm 39% vs 17%; P  =  0.036) with a trend to higher grade (61% vs 48%; P = 0.39). Patients that were initially managed outside a sarcoma unit more often underwent open surgical biopsies (P < 0.0005), had multiple operations (P < 0.0005) and had higher rates of local recurrences (24% vs 6.5%, P  =  0.038). They also had lower 5‐year local recurrence‐free survival rates (P = 0.022), but had higher metastasis‐free survival (P = 0.014). On multivariate analysis, only larger STS size and male gender predicted for poorer metastasis‐free survival (P = 0.042 and 0.018, respectively).

Conclusion

Patients with S‐STS initially managed outside specialized sarcoma units undergo more operations, with risk of greater morbidity, and have greater risk of local recurrence.
FLT3‐ITD positive acute myeloid leukemia: A retrospective analysis of the role of allogeneic transplant and allelic ratio in patient management
Authors: Taylor Emma , Morris Kirk , Ellis Marc , Marlton Paula , Baveshi Ketan , Clarey Joseph , Irving Ian , Cochrane Tara , Kennedy Glen
Published: January 2018

Aim

FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) positive AML is associated with increased relapse risk and reduced overall survival (OS) compared to non‐FLT3‐mutated AML. The aim of this study was to evaluate the impact of allelic ratio and allogeneic transplant on outcomes in FLT3‐ITD+ AML.

Methods

A retrospective study across five centers in Queensland, Australia, was conducted to examine survival outcomes and impact of FLT3‐ITD allelic ratio and allograft.

Results

Seventy‐one patients were included in the study. OS was significantly better for patients who were able to be allografted in first complete remission (CR1; 50.1 months vs 8.5 months; P = 0.0002). We did not find allelic ratio to be predictive of outcome.

Conclusion

Transplantation in first complete remission is associated with improved outcomes for patients with FLT3+ AML. When feasible transplantation in CR1 is recommended. We do not currently recommend using allelic ratio to stratify risk unless this has been validated by local results.
Pacifier use in newborns: related to socioeconomic status but not to early feeding performance
Authors: Pineda Roberta , Luong Anhthi , Ryckman Justin , Smith Joan
Published: January 2018

Aim

Mothers are often advised not to use pacifiers until breastfeeding has been well‐established. This study determined the infant and social factors that were related to pacifier use during the first few days of life and whether it led to alterations in feeding performance.

Methods

We enroled 51 full‐term infants and their mothers at Barnes‐Jewish Hospital in urban St. Louis, USA, in 2015. Before they were discharged the mothers completed a questionnaire, and infant feeding was assessed using a standardised assessment.

Results

There were 24 (47%) infants who used a pacifier during the first few days of life and seven (29%) of these were exclusively breastfed. Pacifier use was less common among mothers who exclusively breastfed (p = 0.04). Pacifier use was more common among mothers whose income was less than 25 000 US dollars (p = 0.02), who were single (p = 0.002) and who did not have a college education (p = 0.03). No associations between pacifier use and feeding performance were observed.

Conclusion

While lower socioeconomic status was related to pacifier use, feeding performance in the first few days of life was no different between those infants who did and did not use pacifiers after a full‐term birth.
Higher Ca2+‐sensitivity of arterial contraction in 1‐week‐old rats is due to a greater Rho‐kinase activity
Authors: Mochalov S. V. , Tarasova N. V. , Kudryashova T. V. , Gaynullina D. K. , Kalenchuk V. U. , Borovik A. S. , Vorotnikov A. V. , Tarasova O. S. , Schubert R.
Published: January 2018

Aim

During early post‐natal development, arterial contraction depends less on Ca2+‐signalling pathways but more on changes in Ca2+‐sensitivity compared to adult animals. Whether this difference is related to Rho‐kinase, one of the major players affecting Ca2+‐sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho‐kinase critically contributes to the higher Ca2+‐sensitivity of contraction in intact arteries of 1‐week‐old rats.

Methods

We studied 1‐week‐old, 4‐ to 5‐week‐old and 10‐ to 12‐week‐old rats performing isometric myography, Ca2+‐fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia.

Results

In 10‐ to 12‐week‐old rats, methoxamine (MX) produced vasoconstriction associated with an increase in [Ca2+]i and Ca2+‐sensitivity. In contrast, in 1‐week‐old rats these contractions were accompanied only by an increase in Ca2+‐sensitivity. All MX‐induced effects were reduced by the Rho‐kinase inhibitor Y‐27632; this reduction was complete only in 1‐week‐old rats. The Rho‐kinase specific site Thr855 on MYPT1 was increasingly phosphorylated by MX in vessels of 1‐week‐old, but not 10‐ to 12‐week‐old rats; this effect was also inhibited completely by Y‐27632. The Rho‐kinase inhibitor fasudil in a dose not affecting the pressor response to MX in 4‐ to 5‐week‐old rats reduced it considerably in 1‐week‐old rats.

Conclusion

Our results suggest that the higher Ca2+‐sensitivity of arterial contraction in 1‐week‐old compared to 10‐ to 12‐week‐old rats is due to a greater Rho‐kinase activity. Constitutively active Rho‐kinase contributes to MX‐induced contraction in 10‐ to 12‐week‐old rats. In 1‐week‐old rats, additional Rho‐kinase activation is involved. This remodelling of the Rho‐kinase pathway is associated with its increased contribution to adrenergic arterial pressure responses.
Mobile phones, gender‐based violence, and distrust in state services: Case studies from Solomon Islands and Papua New Guinea
Authors: Hobbis Stephanie Ketterer
Published: January 2018

This paper examines the potential benefits and pitfalls of mobile phones for accessing social services, particularly in response to gender‐based violence, in Solomon Islands and Papua New Guinea. Drawing on 13 months of ethnographic field research, I show how mobile phones increase rather than decrease perceived distances between social service providers and those they intend to serve. Mobile phones exaggerate the visibility of the shortcomings of the Solomon Islands and Papua New Guinea states and solidify an already entrenched distrust in the state and state services. This distrust is accentuated in experiences with mobile phone‐based mediations of gender‐based violence. Despite the positive influences of mobile phones, they are also recognised as conduits of violence. As such, mobile phones are not only morally ambivalent technologies but also, at times, actively disliked and their use discouraged. This challenges the optimism that surrounds many information and communication technologies for development (ICT4D) projects. When assessing the potentials, successes, and failures of ICT4D programmes, there is a need to pay more attention to the consequences of ‘negative’ or ‘unreliable’ usages of mobile phones as relational technologies.
Glutathione‐PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first‐in‐human study
Authors: Kanhai K. M. S. , Zuiker R. G. J. A. , Stavrakaki I. , Gladdines W. , Gaillard P. J. , Klaassen E. S. , Groeneveld G. J.
Published: January 2018

Aims

Intravenous high‐dose free methylprednisolone (MP) hemisuccinate is the primary treatment for an acute relapse in relapsing–remitting multiple sclerosis. However, it is inconvenient and its side effects are undesirable. Both dose and dosing frequency can be reduced by incorporating free MP in glutathione‐PEGylated liposomes, creating a slow‐release formulation with reduced toxicity and prolonged peripheral efficacy. This first‐in‐human study was designed to assess the safety, pharmacokinetics and pharmacodynamics of glutathione‐PEGylated liposomes containing MP (2B3–201).

Methods

The first part was a double‐blind, three‐way cross over study in 18 healthy male subjects, receiving ascending doses of 2B3–201, active comparator (free MP) or placebo. Part 2 of the study was an open‐label infusion of 2B3–201 (different doses), exploring pretreatment with antihistamines and different infusion schedules in another 18 healthy male subjects, and a cross‐over study in six healthy female subjects. MP plasma concentrations, lymphocyte counts, adrenocorticotropic hormone, osteocalcin and fasting glucose were determined. Safety and tolerability profiles were assessed based on adverse events, safety measurements and central nervous system tests.

Results

The most frequent recorded AE related to 2B3–201 was an infusion related reaction (89%). 2B3–201 was shown to have a plasma half‐life between 24 and 37 h and caused a prolonged decrease in the lymphocyte count, adrenocorticotropic hormone and osteocalcin, and a rise in fasting glucose.

Conclusion

2B3–201 is considered safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events. In addition, 2B3–201 shows a long plasma half‐life and prolonged immunosuppressive effects.
Active retreat of a Late Weichselian marine‐terminating glacier: an example from Melasveit, western Iceland
Authors: Sigfúsdóttir Thorbjörg , Benediktsson Ívar Örn , Phillips Emrys
Published: January 2018

Large and complete glaciotectonic sequences formed by marine‐terminating glaciers are rarely observed on land, hampering our understanding of the behaviour of such glaciers and the processes operating at their margins. During the Late Weichselian in western Iceland, an actively retreating marine‐terminating glacier resulted in the large‐scale deformation of a sequence of glaciomarine sediments. Due to isostatic rebound since the deglaciation, these formations are now exposed in the coastal cliffs of Belgsholt and Melabakkar‐Ásbakkar in the Melasveit district, and provide a detailed record of past glacier dynamics and the inter‐relationships between glaciotectonic and sedimentary processes at the margin of this marine‐terminating glacier. A comprehensive study of the sedimentology and glaciotectonic architecture of the coastal cliffs reveals a series of subaquatic moraines formed by a glacier advancing from Borgarfjörður to the north of the study area. Analyses of the style of deformation within each of the moraines demonstrate that they were primarily built up by ice‐marginal/proglacial thrusting and folding of marine sediments, as well as deposition and subsequent deformation of ice‐marginal subaquatic fans. The largest of the moraines exposed in the Melabakkar‐Ásbakkar section is over 1.5 km wide and 30 m high and indicates the maximum extent of the Borgarfjörður glacier. Generally, the other moraines in the series become progressively younger towards the north, each designating an advance or stillstand position as the glacier oscillated during its overall northward retreat. During this active retreat, glaciomarine sediments rapidly accumulated in front of the glacier providing material for new moraines. As the glacier finally receded from the area, the depressions between the moraines were infilled by continued glaciomarine sedimentation. This study highlights the dynamics of marine‐terminating glaciers and may have implications for the interpretation of their sedimentological and geomorphological records.
Bullying, mental health and friendship in Australian primary school children
Authors: Bayer Jordana K. , Mundy Lisa , Stokes Isobel , Hearps Stephen , Allen Nicholas , Patton George
Published: January 2018

Background

Frequent bullying predicts adolescent mental health problems, particularly depression. This population‐based study with young Australian primary school children aimed to determine the frequency and mental health correlates of bullying, and whether friendship could be protective.

Method

Participants were a population‐based sample of 1221 children aged 8–9 years attending 43 primary schools in metropolitan Melbourne, Australia. Children were taking part in the Childhood to Adolescence Transition Study. Children completed online questionnaires at school to measure peer relations and emotional well‐being. Parents reported on their child's mental health in questionnaires sent to the home.

Results

One in three children (29.2%) reported experiencing frequent bullying, defined as at least once a week. This included physical bullying alone (13.8%), verbal bullying alone (22.7%) and the combination (7.4%). Children who reported being frequently bullied self‐reported higher internalising symptoms compared with children who did not report frequent bullying (M (SD) 1.6 (0.9) vs. 1.1 (0.8), p < .001). This difference was confirmed by parents' reports of their child's internalising symptoms (M (SD) 2.4 (2.3) vs. 2.1 (2.0), p = .026, respectively). Amongst children who reported frequent bullying, those with a group of friends had better emotional well‐being.

Conclusions

A substantial proportion of children report experiencing bullying on a weekly basis early in primary school. Given the prevalence of bullying in primary school and its relationship to children's mental health, we recommend effective school‐wide antibullying programmes. Further research can explore whether intervention to foster a group of friends around bullied children can improve their emotional well‐being.
Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia
Authors: Liu Xiangqiang , Wang Yafang , Sun Li , Min Jie , Liu Jiaming , Chen Di , Zhang Hongbo , Zhang Hongwei , Zhang Helong , Zhou Yongan , Liu Lili
Published: January 2018

Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known whether long, noncoding RNAs (lncRNAs) are involved in the contribution of hypoxia to GC metastasis. In the present study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia‐induced GC cell metastasis. Furthermore, BC005927 is frequently upregulated in GC samples and increased BC005927 expression was correlated with a higher tumor‐node‐metastasis stage. GC patients with higher BC005927 expression had poorer prognoses than those with lower expression. Additional experiments showed that BC005927 expression is induced by hypoxia inducible factor‐1 alpha (HIF‐1α); ChIP assay and luciferase reporter assays confirmed that this lncRNA is a direct transcriptional target of HIF‐1α. Next, we found that EPHB4, a metastasis‐related gene, is regulated by BC005927 and that the expression of EPHB4 was positively correlated with that of BC005927 in the clinical GC samples assessed. Intriguingly, EPHB4 expression was also increased under hypoxia, and its upregulation by BC005927 resulted in hypoxia‐induced GC cell metastasis. These results advance the current understanding of the role of BC005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.
Step‐down of inhaled corticosteroids in non‐eosinophilic asthma: A prospective trial in real life
Authors: Demarche S. , Schleich F. , Henket M. , Paulus V. , Louis R. , Van Hees T.
Published: January 2018

Background

While non‐eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICSs), studies assessing a step‐down of ICS in this specific population are currently lacking.

Objectives

To assess the proportion of non‐eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS.

Methods

This prospective study was completed by 36 non‐eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/μL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver‐operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials.gov, number NCT02169323.

Results

In 14 patients (39%), ICSs were completely withdrawn, and in 10 further patients (28%), ICS were stepped‐down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62‐0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61‐0.93]). After the first step‐down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72‐0.99]).

Conclusions & Clinical Relevance

Withdrawing or reducing the dose of ICS is feasible in two‐thirds of non‐eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS.
Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease‐activated receptor 2 (PAR2)
Authors: Khedr M. E. M. S. , Abdelmotelb A. M. , Pender S. L. F. , Zhou X. , Walls A. F.
Published: January 2018

Background

Tryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2.

Objectives

To investigate the contribution of PAR2 in the pro‐inflammatory actions mediated by tryptase in a mice model.

Methods

We have injected recombinant human βII‐tryptase into the peritoneum of PAR2‐deficient and wild‐type C57BL/6 mice. After 6, 12 and 24 hours, mice were killed, peritoneal lavage performed and inflammatory changes investigated.

Results

Tryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2‐deficient and wild‐type mice. Heat inactivation of tryptase or pre‐incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL‐NH2). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase‐induced MMP2 and MMP9. At 24 hours after tryptase injection, there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat‐inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase‐induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2‐deficient and wild‐type mice.

Conclusions

Our findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Although these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2.
Obese asthmatics are characterized by altered adipose tissue macrophage activation
Authors: Periyalil H. A. , Wood L. G. , Wright T. A. , Karihaloo C. , Starkey M. R. , Miu A. S. , Baines K. J. , Hansbro P. M. , Gibson P. G.
Published: January 2018

Background

Adipose tissue‐derived inflammation is linked to obesity‐related comorbidities. This study aimed to quantify and immuno‐phenotype adipose tissue macrophages (ATMs) from obese asthmatics and obese non‐asthmatics and to examine associations between adipose tissue, systemic and airway inflammation.

Methods

Visceral (VAT) adipose tissue and subcutaneous (SAT) adipose tissue were collected from obese adults undergoing bariatric surgery and processed to obtain the stromovascular fraction. Pro‐inflammatory (M1) and anti‐inflammatory (M2) macrophages were quantified by flow cytometry. Cytospins of induced sputum were stained for differential cell counts. Plasma C‐reactive protein (CRP) and CD163 were measured by ELISA.

Results

VAT contained a higher number of ATMs compared to SAT. A higher percentage of M1 ATMs was observed in VAT of obese asthmatics compared to obese non‐asthmatics. The M1:M2 ratio in VAT was negatively associated with FEV1%. Sputum macrophage count was correlated positively with M1 ATMs and negatively with M2 ATMs in VAT. In obese asthmatics, CRP was positively associated with M1:M2 ratio in VAT. There were no associations with CD163. An elevated ratio of M1:M2 ATMs was observed in VAT of obese asthmatics with increased disease severity.

Conclusions and Clinical Relevance

Visceral inflammation with increased pro‐inflammatory macrophages (M1) occurs in obese asthma and may be a determinant of systemic inflammation and asthma severity.
Epigenetic changes and their implications in autoimmune hepatitis
Authors: Czaja Albert J.
Published: January 2018

Background

The genetic risk of autoimmune hepatitis is insufficient to explain the observed risk, and epigenetic changes may explain disparities in disease occurrence in different populations within and between countries. The goal of this review was to examine how epigenetic changes induced by the environment or inherited as a phenotypic trait may affect autoimmune hepatitis and be amenable to therapeutic intervention.

Materials and methods

Pertinent abstracts were identified in PubMed by multiple search terms. The number of abstracts reviewed was 1689, and the number of full‐length articles reviewed exceeded 150.

Results

Activation of pro‐inflammatory genes in autoimmune disease is associated with hypomethylation of deoxyribonucleic acid and modification of histones within chromatin. Organ‐specific microribonucleic acids can silence genes by marking messenger ribonucleic acids for degradation, and they can promote inflammatory activity or immunosuppression. High circulating levels of the microribonucleic acids 21 and 122 have been demonstrated in autoimmune hepatitis, and they may increase production of pro‐inflammatory cytokines. Microribonucleic acids are also essential for maintaining regulatory T cells. Drugs, pollutants, infections, diet and ageing can induce inheritable epigenetic changes favouring autoimmunity. Reversal is feasible by manipulating enzymes, transcription factors, gene‐silencing molecules and toxic exposures or by administering methyl donors and correcting vitamin D deficiency. Gene targets, site specificity, efficacy and consequences are uncertain.

Conclusions

Potentially reversible epigenetic changes may affect the occurrence and outcome of autoimmune hepatitis, and investigations are warranted to determine the nature of these changes, key genomic targets, and feasible interventions and their consequences.
Within‐diet variation in rates of macronutrient consumption and reproduction does not accompany changes in lifespan in Drosophila melanogaster
Authors: Semaniuk Uliana , Feden'ko Khrystyna , Yurkevych Ihor S. , Storey Kenneth B. , Simpson Stephen J. , Lushchak Oleh
Published: January 2018

Interventions such as caloric or dietary restriction extend lifespan in organisms spanning from yeast to primates. Despite its positive influence on longevity, dietary restriction has been found to negatively affect reproduction. Many studies have reported negative correlations between lifespan and reproductive characteristics (such as mating rate, fecundity, reproductive period, and others). Such correlation gives the appearance of a resource‐based trade‐off between these two life‐history traits. Here, we have used nutritional geometry to confirm previous findings in flies that dietary macronutrient balance (protein‐to‐carbohydrate ratio, P:C) impacts both lifespan and reproduction, such that across a series of diets differing in P:C, maximum lifespan was observed at a lower P:C (1:8) than that which supported highest fecundity (1:1.5). We have then addressed the question whether variation among Drosophila melanogasterMeigen (Diptera: Drosophilidae) fruit flies in food intake and egg production within a single dietary treatment is negatively associated with within‐diet variation in lifespan, as might be expected under a resource‐based trade‐off. There was no such association between intake rate, egg production, and longevity. We noted that the smaller sample sizes and smaller inter‐individual variance apparent within — as compared to across — diet treatments may have weakened any signature of a trade‐off between lifespan and reproduction. Thus, we conclude that, whereas dietary macronutrient ratio is a primary determinant of both reproduction and longevity, neither eating less nor laying fewer eggs per se predicted lifespan. This supports the view that there is not a simple quantitative resource‐based trade‐off between lifespan and reproduction, but rather these represent life‐history traits with qualitatively different nutritional optima.
RBMX is a component of the centromere noncoding RNP complex involved in cohesion regulation
Authors: Cho Yukiko , Ideue Takashi , Nagayama Megumi , Araki Norie , Tani Tokio
Published: January 2018

Satellite I RNA, a noncoding (nc)RNA transcribed from repetitive regions in human centromeres, binds to Aurora kinase B and forms a ncRNP complex required for chromosome segregation. To examine its function in this process, we purified satellite I ncRNP complex from nuclear extracts prepared from asynchronized or mitotic (M) phase‐arrested HeLa cells and then carried out LC/MS to identify proteins bound to satellite I RNA. RBMX (RNA‐binding motif protein, X‐linked), which was isolated from M phase‐arrested cells, was selected for further characterization. We found that RBMX associates with satellite I RNA only during M phase. Knockdown of RBMX induced premature separation of sister chromatid cohesion and abnormal nuclear division. Likewise, knockdown of satellite I RNA also caused premature separation of sister chromatids during M phase. The amounts of RBMX and Sororin, a cohesion regulator, were reduced in satellite I RNA‐depleted cells. These results suggest that satellite I RNA plays a role in stabilizing RBMX and Sororin in the ncRNP complex to maintain proper sister chromatid cohesion.
Ambulatory blood pressure in the dash diet trial: Effects of race and albuminuria
Authors: Tyson Crystal C. , Barnhart Huiman , Sapp Shelly , Poon Victor , Lin Pao‐Hwa , Svetkey Laura P.
Published: January 2018

We evaluated whether low‐grade albuminuria or black race modulates ambulatory blood pressure (BP) or nocturnal BP response to the DASH diet. Among 202 adults enrolled in the DASH multicenter trial who were fed the DASH or control diet for 8 weeks, reductions in 24‐hour daytime and nighttime SBP and DBP were significantly larger for DASH compared to control. Median changes in nocturnal BP dipping were not significant. Compared to urine albumin excretion of <7 mg/d, ≥7 mg/d was associated with larger significant median reductions in 24‐hour SBP (−7.3 vs −3.1 mm Hg), all measures of DBP (24‐hour: −5.9 vs −1.8 mm Hg; daytime: −9.9 vs −4.0 mm Hg; nighttime −9.0 vs −2.0 mm Hg), and with increased nocturnal SBP dipping (2.3% vs −0.5%). Black race was associated with larger median reduction in 24‐hour SBP only (−5.5 vs −2.4 mm Hg). This analysis suggests greater effect of DASH on ambulatory BP in the presence of low‐grade albuminuria.
Human‐simulation‐based learning to prevent medication error: A systematic review
Authors: Sarfati Laura , Ranchon Florence , Vantard Nicolas , Schwiertz Vérane , Larbre Virginie , Parat Stéphanie , Faudel Amélie , Rioufol Catherine
Published: January 2018

Rationale, aims and objectives

In the past 2 decades, there has been an increasing interest in simulation‐based learning programs to prevent medication error (ME). To improve knowledge, skills, and attitudes in prescribers, nurses, and pharmaceutical staff, these methods enable training without directly involving patients. However, best practices for simulation for healthcare providers are as yet undefined. By analysing the current state of experience in the field, the present review aims to assess whether human simulation in healthcare helps to reduce ME.

Methods

A systematic review was conducted on Medline from 2000 to June 2015, associating the terms “Patient Simulation,” “Medication Errors,” and “Simulation Healthcare.” Reports of technology‐based simulation were excluded, to focus exclusively on human simulation in nontechnical skills learning.

Results

Twenty‐one studies assessing simulation‐based learning programs were selected, focusing on pharmacy, medicine or nursing students, or concerning programs aimed at reducing administration or preparation errors, managing crises, or learning communication skills for healthcare professionals.

The studies varied in design, methodology, and assessment criteria. Few demonstrated that simulation was more effective than didactic learning in reducing ME. This review highlights a lack of long‐term assessment and real‐life extrapolation, with limited scenarios and participant samples. These various experiences, however, help in identifying the key elements required for an effective human simulation‐based learning program for ME prevention: ie, scenario design, debriefing, and perception assessment. The performance of these programs depends on their ability to reflect reality and on professional guidance.

Conclusion

Properly regulated simulation is a good way to train staff in events that happen only exceptionally, as well as in standard daily activities. By integrating human factors, simulation seems to be effective in preventing iatrogenic risk related to ME, if the program is well designed.
Reflectance difference microscopy for nanometre thickness microstructure measurements
Authors: HU C. , HUO S. , SHEN W. , LI Y. , HU X.
Published: January 2018

The discontinuity of medium at the boundary produces optically anisotropic response which makes reflectance difference microscopy (RDM) a potential method for nanometre‐thickness microstructure measurements. Here, we present the methodology of RDM for the edge measurement of ultrathin microstructure. The RD signal of microstructure's boundary is mathematically deduced according to boundary condition and polarization optics theory. A normal‐incidence RDM setup was built simply with one linear polarizer, one liquid crystal variable retarder and one 5 × objective. Then, the performance of the developed setup was identified using homogenous reflection mirror and high quality linear polarizer. For demonstration, microstructures array with 100 nm step height was measured. The results show that the RD signal is sensitive to the edge and its sign reflects the change direction of the edge. Furthermore, a height sensitivity of better than 10 nm and a spatial resolution of ∼3 m offer this technique a good candidate for characterizing ultrathin microstructures.
Itraconazole induced hypertension and hypokalemia: Mechanistic evaluation
Authors: Hoffmann Wesley J. , McHardy Ian , Thompson George R.
Published: January 2018

We describe a case of apparent mineralocorticoid excess (hypertension, hypokalemia, metabolic alkalosis and low plasma renin activity) secondary to itraconazole therapy. Inhibition of 11β‐hydroxysteroid dehydrogenase 2 was demonstrated, and withholding itraconazole led to resolution of adverse effects that did not recur with voriconazole. This report adds to a growing body of evidence linking apparent mineralocorticoid excess with certain triazoles.
Diagnostic patterns and delays in autoimmune blistering diseases of the mouth: A cross‐sectional study
Authors: Hassona Y , Cirillo N , Taimeh D , Al Khawaldeh H , Sawair F
Published: January 2018

Objectives

To describe the natural history and factors influencing diagnostic delays among patients with autoimmune blistering diseases of the mouth.

Materials and Methods

In this cross‐sectional study, 27 newly diagnosed patients were interviewed, and professional and patient delays were calculated. Disease extent and severity scores were determined using Saraswat scoring system.

Results

Twenty‐seven patients were interviewed and examined. Patient delay was significantly longer in patients who had desquamative gingivitis as initial presentation, in those who tried to use home remedies and over the counter medications, and in patients with less severe disease. Most patients (n = 21 [77.7%]) made more than one consultation, and the mean time needed to reach a definitive diagnosis (i.e. professional delay) was 83.2 ± 21.4 days (range from 21 to 130 days). Professional delay was significantly correlated with the number of previous consultations (r = .78) and was significantly longer in patients who had desquamative gingivitis as initial presentation.

Conclusion

Diagnosis of oral blistering diseases is often delayed. Diagnostic delay is more common in patients presenting with desquamative gingivitis and those with less severe disease. Improving patients and healthcare professionals’ awareness about oral blistering diseases might help reduce diagnostic delay.
Comparing human and mouse salivary glands: A practice guide for salivary researchers
Authors: Maruyama CL , Monroe MM , Hunt JP , Buchmann L , Baker OJ
Published: January 2018

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.
Validity and Test–Retest Reliability of the Dutch Modified Perceived Deficits Questionnaire to Examine Cognitive Symptoms in Women with Chronic Whiplash, Chronic Idiopathic Neck Pain, and Fibromyalgia
Authors: Lenoir D. , De Pauw R. , Ickmans K. , Schumacher C. , Timmers I. , Kregel J. , Coppieters I.
Published: January 2018

Introduction

Until now, only reliability and validity of the English version of the modified Perceived Deficits Questionnaire (mPDQ) have been investigated.

Objective

The aim of this study was to translate the mPDQ into Dutch and evaluate its validity and reliability as an assessment tool for self‐perceived cognitive problems in patients with chronic whiplash‐associated disorders (CWAD), chronic idiopathic neck pain (CINP), and fibromyalgia (FM).

Methods

A case–control study was performed with a volunteer sample of 13 women with CWAD, 18 with CINP, and 33 with FM, and 33 women who were healthy and free of pain. The mPDQ was first translated into Dutch, and its test–retest reliability, internal consistency, and discriminative power were examined.

Results

The intraclass correlation coefficients were higher than 0.74. Cronbach's α values ranged between 0.71 and 0.95. Total mPDQ scores were significantly higher (P < 0.017) in FM and CWAD patients compared to healthy controls. Furthermore, participants performed the Stroop task and the psychomotor vigilance task (PVT), 2 neuropsychological computer‐based cognitive performance tests. Correlations between the mPDQ total score and the cognitive performance tests were evaluated. Significant moderate to high correlations were found in all study samples between total mPDQ score and objective cognitive tests (Spearman correlation coefficient = 0.35 to 0.80; P < 0.05).

Conclusion

Therefore, the Dutch version of the mPDQ showed high test–retest reliability and high internal consistency, and was able to distinguish CWAD and FM patients from healthy controls.

Perspective

This article presents the validity and test–retest reliability of the Dutch mPDQ. This measure could help clinicians who seek a reliable and user‐friendly way to assess cognitive symptoms in chronic pain patients.
If or when? Uncertainty's role in anxious anticipation
Authors: Bennett Ken P. , Sinclair Jac V. , Larson Christine L.
Published: January 2018

Uncertainty is often associated with subjective distress and a potentiated anxiety response. Occurrence uncertainty, or the inability to predict if a threat will occur, has rarely been compared experimentally with temporal uncertainty, or the inability to predict when a threat will occur. The current study aimed to (a) directly compare the anxiogenic effects of anticipating these two types of uncertain threat, as indexed by the eyeblink startle response, and (b) assess the relationship between startle response to occurrence and temporal uncertainty and individual differences in self‐reported intolerance of uncertainty and anxiety. The findings indicated that anticipation during occurrence uncertainty elicited a larger startle response than anticipating a certain threat, but anticipation during temporal uncertainty was superior at potentiating startle blink overall. Additional analyses of the effects of order and habituation further highlighted temporal uncertainty's superiority in eliciting greater startle responding. This suggests that, while uncertainty is physiologically anxiety provoking, some level of certainty that the threat will occur enhances the robustness of the physiological anxiety response. However, self‐reported anxiety was equivalent for temporal and occurrence uncertainty, suggesting that, while defensive responding may be more affected by temporal uncertainty, people perceive both types of uncertainty as anxiogenic. Individual differences in the intolerance of uncertainty and other anxiety measures were not related to anticipatory startle responsivity during any of the conditions.
The South China Sea arbitration: Environmental obligations under the Law of the Sea Convention
Authors: Tanaka Yoshifumi
Published: January 2018

This case note analyses the marine environmental protection issues that arose in the 2016 South China Sea arbitration. Given that the South China Sea includes highly productive fisheries and extensive coral reef ecosystems, the alleged breach of environmental obligations under the United Nations (UN) Convention on the Law of the Sea was important in this arbitration. The Arbitral Tribunal examined three obligations concerning marine environmental protection under the UN Convention on the Law of the Sea: the obligation of due diligence; the obligation to conduct an environmental impact assessment; and the obligation to cooperate. The Tribunal's arbitral award contributes to the clarification of the interpretation of relevant provisions concerning marine environmental protection under the Convention. Furthermore, a remarkable feature of the arbitration was that the Tribunal appointed experts to have an independent opinion with regard to environmental damages arising from China's activities in the South China Sea. The use of experts in the South China Sea arbitration is worth noting, since scientific evidence is of particular importance in the settlement of international environmental disputes.
High‐frequency ultrasonography—New non‐invasive method in assessment of skin lymphomas
Authors: Polańska A. , Dańczak‐Pazdrowska A. , Olek‐Hrab K. , Osmola‐Mańkowska A. , Bowszyc‐Dmochowska M. , Żaba R. , Adamski Z.
Published: January 2018

Background

Mycosis fingoides (MF) is the most common subtype of primary cutaneous T‐cell lymphomas. Current evaluation of disease extent and severity is based on mSWAT scoring system, which seems to be relatively subjective. The aim of this subject was to present the usefulness of 20 MHz in objective 5‐year long monitoring of response to therapy in MF patients.

Materials and methods

The 5‐years long follow‐up based on 19 skin USG images of patients diagnosed as early stages of MF was studied. The assessed USG parameter was the mean diameter of subepidermal low echogenic band (SLEB).

Results

In every MF patient during exacerbation within lesional skin we could observe SLEB, which thinning or complete disappearance was detected after finishing the therapy. Lack of complete absence of SLEB was related to the lack of complete remission assessed by mSWAT.

Conclusion

We present for the first time the possibility of monitoring patients’ clinical state on the base of non‐invasive USG imaging. We recommend additional use of 20 MHz USG to reduce intra‐observer variability and to assess residual disease. USG imaging can complement evaluation of skin lesions in MF and can support clinical judgement.
Probability Theory Plus Noise: Descriptive Estimation and Inferential Judgment
Authors: Costello Fintan , Watts Paul
Published: January 2018

We describe a computational model of two central aspects of people's probabilistic reasoning: descriptive probability estimation and inferential probability judgment. This model assumes that people's reasoning follows standard frequentist probability theory, but it is subject to random noise. This random noise has a regressive effect in descriptive probability estimation, moving probability estimates away from normative probabilities and toward the center of the probability scale. This random noise has an anti‐regressive effect in inferential judgement, however. These regressive and anti‐regressive effects explain various reliable and systematic biases seen in people's descriptive probability estimation and inferential probability judgment. This model predicts that these contrary effects will tend to cancel out in tasks that involve both descriptive estimation and inferential judgement, leading to unbiased responses in those tasks. We test this model by applying it to one such task, described by Gallistel et al. ). Participants' median responses in this task were unbiased, agreeing with normative probability theory over the full range of responses. Our model captures the pattern of unbiased responses in this task, while simultaneously explaining systematic biases away from normatively correct probabilities seen in other tasks.
Enhancing heterologous expression in Chlamydomonas reinhardtii by transcript sequence optimization
Authors: Weiner Iddo , Atar Shimshi , Schweitzer Shira , Eilenberg Haviva , Feldman Yael , Avitan Meital , Blau Mor , Danon Avihai , Tuller Tamir , Yacoby Iftach
Published: January 2018

Various species of microalgae have recently emerged as promising host‐organisms for use in biotechnology industries due to their unique properties. These include efficient conversion of sunlight into organic compounds, the ability to grow in extreme conditions and the occurrence of numerous post‐translational modification pathways. However, the inability to obtain high levels of nuclear heterologous gene expression in microalgae hinders the development of the entire field. To overcome this limitation, we analyzed different sequence optimization algorithms while studying the effect of transcript sequence features on heterologous expression in the model microalga Chlamydomonas reinhardtii, whose genome consists of rare features such as a high GC content. Based on the analysis of genomic data, we created eight unique sequences coding for a synthetic ferredoxin–hydrogenase enzyme, used here as a reporter gene. Following in silico design, these synthetic genes were transformed into the C. reinhardtii nucleus, after which gene expression levels were measured. The empirical data, measured in vivo show a discrepancy of up to 65‐fold between the different constructs. In this work we demonstrate how the combination of computational methods and our empirical results enable us to learn about the way gene expression is encoded in the C. reinhardtii transcripts. We describe the deleterious effect on overall expression of codons encoding for splicing signals. Subsequently, our analysis shows that utilization of a frequent subset of preferred codons results in elevated transcript levels, and that mRNA folding energy in the vicinity of translation initiation significantly affects gene expression.
Transfusion‐transmitted and community‐acquired babesiosis in New York, 2004 to 2015
Authors: Linden Jeanne V. , Prusinski Melissa A. , Crowder Lauren A. , Tonnetti Laura , Stramer Susan L. , Kessler Debra A. , White Jennifer , Shaz Beth , Olkowska Danuta
Published: January 2018

BACKGROUND

Babesiosis is a potentially life‐threatening zoonotic infection most frequently caused by the intraerythrocytic parasite Babesia microti. The pathogen is usually tickborne, but may also be transfusion or vertically transmitted. Healthy persons, including blood donors, may be asymptomatic and unaware they are infected. Immunocompromised patients are at increased risk for symptomatic disease.

STUDY DESIGN AND METHODS

All reported community‐acquired babesiosis cases in New York from 2004 to 2015 were evaluated, enumerated, and characterized. All potential transfusion‐transmitted babesiosis (TTB) cases reported through one or more of three public health surveillance systems were investigated to determine the likelihood of transfusion transmission. In addition, host‐seeking ticks were actively collected in public parks and other likely sites of human exposure to B. microti.

RESULTS

From 2004 to 2015, a total of 3799 cases of babesiosis were found; 55 (1.4%) of these were linked to transfusion. The incidence of both community‐acquired babesiosis and TTB increased significantly during the 12‐year study period. The geographic range of both ticks and tickborne infections also expanded. Among TTB cases, 95% of recipients had at least one risk factor for symptomatic disease. Implicated donors resided in five states, including in 10 New York counties. More than half of implicated donors resided in counties known to be B. microti endemic.

CONCLUSION

The increasing incidence of TTB correlated with increases in community‐acquired babesiosis and infection of ticks with B. microti. Surveillance of ticks and community‐acquired cases may aid identification of emerging areas at risk for Babesia transfusion transmission.