bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic and ecological diversity of apusomonads, a lineage of deep‐branching eukaryotes
Authors: Torruella Guifré , Moreira David , López‐García Purificación
Published: November 2016

Apusomonads are a mysterious group of heterotrophic gliding biflagellates branching deeply in the eukaryotic tree of life as sister group to opisthokonts (including animals, fungi, and a variety of unicellular protists). Despite their evolutionary interest, their diversity and ecology remain largely unknown, with very few described species and environmental sequences in databases. Most environmental 18S rRNA gene‐based studies generally fail to identify apusomonad sequences, which might be due to primer bias, low abundance, and/or to the fact that their biotopes remain poorly explored. We have carried out an extensive search of 18S rRNA genes using an apusomonad‐specific primer in a wide variety of ecosystems. Our study significantly broadens the diversity of apusomonads showing that, despite being mostly rare protists, they often dwell in freshwater and marine benthic environments, generally associated with low‐oxygen concentrations. Apusomonads have been identified in environments across a wide salinity range. Some operational taxonomic units (OTUs), occurring in both marine and freshwater ecosystems, seem truly euryhaline, indicating that members of this deep‐branching lineage easily cross such ecological barriers.
The Rate of Change in Alcohol Misuse Across Adolescence is Heritable
Authors: Edwards Alexis C. , Heron Jon , Vladimirov Vladimir , Wolen Aaron R. , Adkins Daniel E. , Aliev Fazil , Hickman Matthew , Kendler Kenneth S.
Published: November 2016

Background

Alcohol use typically begins during adolescence and escalates into young adulthood. This represents an important period for the establishment of alcohol use and misuse patterns, which can have psychosocial and medical consequences. Although changes in alcohol use during this time have been phenotypically characterized, their genetic nature is poorly understood.

Methods

Participants of the Avon Longitudinal Study of Parents and Children completed the Alcohol Use Disorders Identification Test (AUDIT) 4 times from age 16 to 20. We used Mplus to construct a growth model characterizing changes in AUDIT scores across time (N = 4,545, where data were available for at least 2 time points). The slope of the model was used as the phenotype in a genomewide association study (N = 3,380), followed by secondary genetic analyses.

Results

No individual marker met genomewide significance criteria. Top markers mapped to biologically plausible candidate genes. The slope term was moderately heritable (h2SNP = 0.26, p = 0.009), and replication attempts using a meta‐analysis of independent samples provided support for implicated variants at the aggregate level. Nominally significant (p < 0.00001) markers mapped to putatively active genomic regions in brain tissue more frequently than expected by chance.

Conclusions

These results build on prior studies by demonstrating that common genetic variation impacts alcohol misuse trajectories. Influential loci map to genes that merit additional research, as well as to intergenic regions with regulatory functions in the central nervous system. These findings underscore the complex biological nature of alcohol misuse across development.
Unexpected motor weakness following quadratus lumborum block for gynaecological laparoscopy
Authors: Wikner M.
Published: November 2016

Quadratus lumborum block has recently been described as an effective and long‐lasting analgesic strategy for various abdominal operations, including gynaecological laparoscopy. Despite evidence that the analgesic effect is mediated by indirect paravertebral block and that local anaesthetic spreads to the lumbar paravertebral space, there have been no reports to date of lower limb motor weakness. We present a patient with unilateral hip flexion and knee extension weakness leading to unplanned overnight admission following lateral quadratus lumborum block with 20 ml levobupivacaine 0.25%. The L2 dermatomal sensory loss and hip flexion weakness suggested spread to either the L2 paravertebral space or to the lumbar plexus, causing weakness of the psoas and iliacus muscles and possibly the quadriceps. The duration of motor block was approximately 18 h. This complication should be considered when performing the block, especially in the setting of day‐case surgery.
Preliminary study of personality traits in Chinese lung cancer patients: Modification by neurotensin receptor 1 polymorphisms
Authors: Ma Hui , Cong Zhengtu , Zhang Hongyu , Tao Jiangang , Yang Chao , Song Zhijie
Published: November 2016

This study recruited 148 lung cancer patients and 157 healthy Chinese individuals to evaluate the personality traits of Chinese lung cancer patients using the Tridimensional Personality Questionnaire and to investigate the associations between these traits and the rs6090453C/G and rs6011914C/G polymorphisms of the neurotensin receptor 1 gene. The results demonstrated significant differences in the Tridimensional Personality Questionnaire total and subscale scores between the 2 groups. Significant differences were found in the reward dependence 2 (RD2) score between the rs6090453C/G genotypes and in the total harm avoidance (HA), HA1, HA2, HA4, and RD2 scores between the rs6011914C/G genotypes. Thus, patients with lung cancer have specific personality traits, and variations in the neurotensin receptor 1 gene may be involved in the biological mechanisms of the HA and RD personality traits.
Effect of dietary kapok oil supplementation on growth performance, carcass traits, meat quality and sensory traits of pork in finishing‐pigs
Authors: Maeda Keisuke , Kohira Kimiko , Kubota Hiroki , Yamanaka Kousuke , Saito Kaoru , Irie Masakazu
Published: November 2016

Kapok seed and oil from the tropical zone are widely used as pig feed to harden porcine fat in Japan. This study evaluated the effect of dietary kapok oil supplementation on pork quality and sensory traits. Five Duroc pigs each were assigned to an experimental group supplemented with kapok oil and a control group. Dietary kapok oil supplementation had no effect on growth performance and intramuscular fat content in the Longissimus dorsi muscle (LM). Supplemental kapok oil increased saturated fatty acid contents in subcutaneous and intramuscular fat and decreased monounsaturated fatty acid levels (P < 0.05). Off‐flavor detection by a trained panel was higher in the experimental than the control group (P < 0.05), but tenderness, juiciness, texture and flavor intensity of LM chops were similar in both groups. The overall palatability of pork as judged by a consumer panel decreased with kapok oil supplementation (P < 0.01). These results indicate that while growth performance, intramuscular fat contents and carcass characteristics were unchanged, while dietary kapok oil supplementation makes firm fat to prevent inferior soft fat in pork, it can lower the palatability of pork due to a decrease in monounsaturated fatty acids.
Milking performance evaluation and factors affecting milking claw vacuum levels with flow simulator
Authors: Enokidani Masafumi , Kawai Kazuhiro , Shinozuka Yasunori , Watanabe Aiko
Published: November 2016

Milking performance of milking machines that matches the production capability of dairy cows is important in reducing the risk of mastitis, particularly in high‐producing cows. This study used a simulated milking device to examine the milking performance of the milking system of 73 dairy farms and to analyze the factors affecting claw vacuum. Mean claw vacuum and range of fluctuation of claw vacuum (claw vacuum range) were measured at three different flow rates: 5.7, 7.6 and 8.7 kg/min. At the highest flow rate, only 16 farms (21.9%) met both standards of mean claw vacuum ≥35 kPa and claw vacuum range ≤ 7 kPa, showing that milking systems currently have poor milking performance. The factors affecting mean claw vacuum were claw type, milk‐meter and vacuum shut‐off device; the factor affecting claw vacuum range was claw type. Examination of the milking performance of the milking system using a simulated milking device allows an examination of the performance that can cope with high producing cows, indicating the possibility of reducing the risk of mastitis caused by inappropriate claw vacuum.
Multi-Parameter Regression Survival Modeling: An Alternative to Proportional Hazards
Authors: Burke K. , MacKenzie G.
Published: November 2016

It is standard practice for covariates to enter a parametric model through a single distributional parameter of interest, for example, the scale parameter in many standard survival models. Indeed, the well-known proportional hazards model is of this kind. In this article, we discuss a more general approach whereby covariates enter the model through more than one distributional parameter simultaneously (e.g., scale and shape parameters). We refer to this practice as “multi-parameter regression” (MPR) modeling and explore its use in a survival analysis context. We find that multi-parameter regression leads to more flexible models which can offer greater insight into the underlying data generating process. To illustrate the concept, we consider the two-parameter Weibull model which leads to time-dependent hazard ratios, thus relaxing the typical proportional hazards assumption and motivating a new test of proportionality. A novel variable selection strategy is introduced for such multi-parameter regression models. It accounts for the correlation arising between the estimated regression coefficients in two or more linear predictors—a feature which has not been considered by other authors in similar settings. The methods discussed have been implemented in the mpr package in R.
A Risk-Based Measure of Time-Varying Prognostic Discrimination for Survival Models
Authors: Liang C. Jason , Heagerty Patrick J.
Published: November 2016

Prognostic survival models are commonly evaluated in terms of both their calibration and their discrimination. Comparing observed and predicted survival curves can assess calibration, while discrimination is typically summarized through comparison of the properties of cases or subjects who experience an event, and the properties of controls represented by event-free individuals. For binary data, discrimination is characterized either by using the relative ranks of cases and controls and a receiver operating characteristic (ROC) curve, or by summarizing the magnitude of risk placed on cases and controls through calculation of the discrimination slope (DS). In this article, we propose a risk-based measure of time-varying discrimination that generalizes the discrimination slope to allow use with incident events and hazard models. We refer to the new measure as the hazard discrimination summary (HDS) since it compares the relative risk among incident cases to their associated dynamic risk set controls. We introduce both a model-based estimation procedure that adopts the Cox model, and an alternative approach that locally relaxes the proportional hazards assumption. We illustrate the proposed methods using both a benchmark survival data set, and an oncology study where primary interest is in the time-varying performance of candidate biomarkers.
IMPACT OF OUTCOME AMBIGUITY ON SELF‐INSURANCE AND SELF‐PROTECTION: EXPERIMENTAL EVIDENCE
Authors: Ozdemir Ozlem
Published: November 2016

This experimental study examines and compares individual valuations of the two risk reduction mechanisms: self‐insurance and self‐protection in risky versus ambiguous outcome situations. Results confirm that individuals do not perceive these mechanisms differently under risk. Moreover, ambiguity in the outcome (i.e., size of loss) affects valuations weakly, and changing representations of ambiguity do not alter valuation. In general, individuals are found to be ambiguity averse for low sizes of loss and ambiguity neutral for high sizes of loss, regardless of the probability of loss. Finally, no strong support is found for any particular model of ambiguity.
Geographic variation in genetic and demographic performance: new insights from an old biogeographical paradigm
Authors: Pironon Samuel , Papuga Guillaume , Villellas Jesús , Angert Amy L. , García María B. , Thompson John D.
Published: November 2016

The ‘centre–periphery hypothesis’ (CPH) is a long‐standing postulate in ecology that states that genetic variation and demographic performance of a species decrease from the centre to the edge of its geographic range. This hypothesis is based on an assumed concordance between geographical peripherality and ecological marginality such that environmental conditions become harsher towards the limits of a species range. In this way, theCPHsets the stage for understanding the causes of distribution limits. To date, no study has examined conjointly the consistency of these postulates. In an extensive literature review we discuss the birth and development of theCPHand provide an assessment of theCPHby reviewing 248 empirical studies in the context of three main themes. First, a decrease in species occurrence towards their range limits was observed in 81% of studies, while only 51% demonstrated reduced abundance of individuals. A decline in genetic variation, increased differentiation among populations and higher rates of inbreeding were demonstrated by roughly one in two studies (47, 45 and 48%, respectively). However, demographic rates, size and population performance less often followedCPHexpectations (20–30% of studies). We highlight the impact of important methodological, taxonomic, and biogeographical biases on such validation rates. Second, we found that geographic and ecological marginality gradients are not systematically concordant, which casts doubt on the reliability of a main assumption of theCPH. Finally, we attempt to disentangle the relative contribution of geographical, ecological and historical processes on the spatial distribution of genetic and demographic parameters. While ecological marginality gradients explain variation in species' demographic performance better than geographic gradients, contemporary and historical factors may contribute interactively to spatial patterns of genetic variation. We thereby propose a framework that integrates species' ecological niche characteristics together with current and past range structure to investigate spatial patterns of genetic and demographic variation across species ranges.
A comparison of parent and childcare provider's attitudes and perceptions about preschoolers' physical activity and outdoor time
Authors: Tandon P. S. , Saelens B. E. , Copeland K. A.
Published: November 2016

Background

Young children depend on adult caregivers to provide opportunities for physical activity. Research has focused on barriers and facilitators to children's physical activity while in childcare, but parental influences remain largely unknown. This study examines parent's attitudes about preschoolers' physical activity and outdoor time, compares them with those of childcare providers and determines the association between parental attitudes and preschoolers' measured activity.

Methods

Parents and childcare providers from 30 childcare centres were surveyed regarding attitudes towards preschoolers' physical activity and outdoor time. Children's moderate‐to‐vigorous physical activity was determined by using 24‐h accelerometry. Parent and childcare providers' responses were compared. Mixed‐effect linear regression examined moderate‐to‐vigorous physical activity and sedentary time as outcomes with parental attitudes as predictors, family demographics as covariates and centre as a random effect.

Results

Three hundred eighty‐eight parents and 151 childcare providers participated. On average, children were 4.3 (0.7) years old. Parents and childcare providers both considered daily physical activity important for preschoolers, but providers rated the importance of daily outdoor time higher on a 10‐point scale (8.9 vs. 7.6, P < 0.001). More parents than providers believed that children would get sick by playing outside in the cold (25 vs. 11%, P < 0.05). Parents were more comfortable with their child playing outside at childcare compared with outside at home (8.9 vs. 6.9, P < 0.001). Lower income parents felt less comfortable than higher income parents with their child playing outside either near home or at childcare. Neither home nor total child activity levels were associated with most parental attitudes queried.

Conclusions

While parents and childcare providers value daily physical activity for children, some parents expressed discomfort about their young children engaging in outdoor play, especially around home and in cold weather. These findings highlight the importance of childcare‐based interventions to promote preschoolers' physical activity and outdoor play.
Exenatide induces an increase in vasodilatory and a decrease in vasoconstrictive mediators
Authors: Chaudhuri Ajay , Ghanim Husam , Makdissi Antoine , Green Kelly , Abuaysheh Sanaa , Batra Manav , D. Kuhadiya Nitesh , Dandona Paresh
Published: November 2016

In view of the known vasodilatory effects of glucagon‐like peptide‐1 and exenatide, we investigated the effects of exenatide on vasoactive factors. We analysed blood samples and mononuclear cells (MNCs) from a previous study, collected after a single dose and 12 weeks of exenatide or placebo treatment in a series of 24 patients with type 2 diabetes mellitus. After exenatide treatment, plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNCs increased significantly after a single dose. Angiotensinogen concentration fell significantly 2 hours after a single dose and at 12 weeks, while renin and angiotensin II levels fell significantly only after a single dose and not after 12 weeks of treatment. Exenatide also suppressed the plasma concentration of transforming growth factor‐β and the expression of P311 in MNCs at 12 weeks. Thus, exenatide induces an increase in a series of vasodilators, while suppressing the renin‐angiotensin system. These changes may contribute to the overall vasodilatory effect of exenatide.
Parentally acquired differences in resource acquisition ability between brown trout from alternative life history parentage
Authors: Hughes Martin R. , Van Leeuwen Travis E. , Cunningham Peter D. , Adams Colin E.
Published: November 2016

Dominance hierarchies, where they exist, affect individual food acquisition ability and fitness, both of which have the potential to influence life history pathways. Juvenile salmonids exhibit clear dominance hierarchies in early life. As one of the drivers for the adoption of alternative life histories in salmonids is the relative rate of resource acquisition, there is potential for juvenile behaviour to influence the subsequent life history strategy of the individual. Lacustrine brown trout, Salmo trutta, exhibit a multitude of life histories which includes among others the piscivorous (ferox) life history where individuals grow to large size and have delayed maturity and benthivorous and pelagic life histories where individuals grow to much smaller sizes, however mature earlier. Using a number of observable characteristics of dominance, this study compared differences in behaviour between size‐matched pairs of progeny, reared under common garden conditions which are derived from alternative, co‐existing life history strategy parents. We found that first‐generation progeny of ferox trout were more aggressive, acquired more food, had lighter skin pigmentation and held more desirable positions than the progeny of benthivorous brown trout in an experimental stream system. Ferox trout progeny were dominant over benthivorous brown trout progeny in 90% of trials in dyadic contests. Given such clear differences in dominance, this study indicates that parentally acquired dominance‐related differences, passed through either, or both, of genetic and nongenetic (e.g. maternal effects) means, are likely a contributing factor to the continued maintenance of distinct life history strategies of brown trout.
Sharecropping was sometimes efficient: sharecropping with compensation for improvements in European viticulture†
Authors: Garrido Samuel
Published: November 2016

There is no consensus among specialists in agricultural contracts over whether the long‐term inefficiencies that classical economists attributed to sharecropping actually exist. This article maintains that they do exist and are partly caused by the fact that sharecropping is hardly compatible with the tenant being compensated for improvements, viticulture being the main historical exception. In line with recent contributions to the sharecropping literature, the article contends that the widely held belief among scholars of agricultural contracts that sharecropping was very frequent in Europe's vineyards is incorrect. However, it also provides evidence of an issue whose importance has gone largely unnoticed: prior to the twentieth century, many of the European vineyards worked by sharecroppers had been created by the sharecroppers themselves, through contracts which entitled them to compensation. Those contracts abounded while viticulture depended basically on two inputs, land and labour. When viticulture became a heavy consumer of capital, they were rapidly abandoned, but not in Catalonia, with a paradoxical result: the Catalan rabassa morta contract, which for centuries had made it possible to eliminate both the long‐ and short‐term inefficiencies of sharecropping, ended up becoming an obstacle to overcoming the short‐term inefficiencies. The article discusses why that happened.
Safety profiles of iron chelators in young patients with haemoglobinopathies
Authors: Botzenhardt Sebastian , Li Niya , Chan Esther W. , Sing Chor Wing , Wong Ian C. K. , Neubert Antje
Published: November 2016

Background

This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr of age with haemoglobinopathies.

Methods

Searches in electronic literature databases were performed. Studies reporting adverse events associated with iron chelation therapy were included. Study and reporting quality was assessed using AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms. Prospective clinical studies were pooled in a random‐effects meta‐analysis of proportions.

Results

Safety data of 2040 patients from 34 studies were included. Ninety‐two case reports of 246 patients were identified. DFX (937 patients) and DFP (667 patients) possess the largest published safety evidence. Fewer studies on combination regimens are available. Increased transaminases were seen in all regimens (3.9–31.3%) and gastrointestinal disorders with DFP and DFX (3.7–18.4% and 5.8–18.8%, respectively). Therapy discontinuations due to adverse events were low (0–4.1%). Reporting quality was selective and poor in most of the studies.

Conclusion

Iron chelation therapy is generally safe in young patients, and published data correspond to summary of product characteristics. Each iron chelation regimen has its specific safety risks. DFO seems not to be associated with serious adverse effects in recommended doses. In DFP and DFX, rare, but serious, adverse reactions can occur. Data on combined therapy are scarce, but it seems equally safe compared to monotherapy.
Anthropometrics and prognosis in diffuse large B‐cell lymphoma: a multicentre study of 653 patients
Authors: Bendtsen Mette Dahl , Munksgaard Peter Svenssen , Severinsen Marianne Tang , Bekric Eric , Brieghel Christian , Nielsen Kristina Buchardi , Brown Peter de Nully , Dybkær Karen , Johnsen Hans Erik , Bøgsted Martin , El‐Galaly Tarec Christoffer
Published: November 2016

Objective

The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B‐cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients.

Patients and methods

A total of 653 R‐CHOP(‐like)‐treated DLBCL patients were included in this retrospective cohort study. Patients, baseline clinicopathologic characteristics and treatment information were retrieved from the Danish Lymphoma Registry. Anthropometric measures were obtained from chemotherapy prescription charts.

Results

Underweight (BMI <18.5 kg/m2) was associated with significantly worse progression‐free survival (PFS) for male patients only in sex‐stratified analyses (HR 3.92, 95% CI: 1.57–9.75, P = 0.003, for males; HR 1.65, 95% CI: 0.90–3.02, P = 0.107, for females). In multivariate analyses, underweight was associated with worse PFS for both sexes (HR 5.34, 95% CI: 2.07–13.79, P = 0.001, for males; HR 2.14, 95% CI: 1.12–4.08, P = 0.021, for females). Similar results were obtained in analyses of overall survival. In crude analyses, BSA <1.8 m2 was associated with worse PFS for men and women (HR 1.65, 95% CI: 1.03–2.65, P = 0.039, for men; HR 1.62, 95% CI: 1.03–2.56, P = 0.037, for women). In multivariate analyses, however, these associations diminished.

Conclusions

Our study demonstrates that underweight DLBCL patients have worse outcomes following R‐CHOP as compared to normal as well as overweight patients.
Synaesthesia lost and found: two cases of person‐ and music‐colour synaesthesia
Authors: Farina Francesca R. , Mitchell Kevin J. , Roche Richard A. P.
Published: November 2016

Synaesthesia is a developmental condition involving cross‐communication between sensory modalities or substreams whereby an inducer (e.g. a sound) automatically evokes a concurrent percept in another modality (e.g. a colour). Whether this condition arises due to atypical structural connectivity (e.g., between normally unconnected cortical areas) or altered neurochemistry remains a central question. We report the exceptional cases of two synaesthetes – subjects AB and CD – both of whom experience coloured auras around individuals, as well as coloured perceptions in response to music. Both subjects have, in recent years, suffered a complete loss or reduction of their synaesthetic experiences, one (AB) through successive head traumas, including a lightning strike, followed by a number of medications, and the other (CD) while taking anxiolytic medications. Using semi‐structured interviews and data from the Synaesthesia Battery and a colourpicker task, we characterize the phenomenological characteristics of their pre‐loss synaesthesia, as well as the subsequent restoration of each subject's synaesthetic experiences (in the months post‐trauma for AB, and after cessation of medication for CD). Even after years of suppression, the patterns of associations were highly consistent with those experienced pre‐injury. The phenomenological experience of synaesthesia can, thus, like most conscious experiences, be modulated by pharmacologically diverse medications or head injury. However, the underlying neural substrates mediating specific synaesthetic pairings appear remarkably ‘hard‐wired’ and can persist over very long periods even under conditions that alter or completely suppress the conscious synaesthetic experience itself.
JAK inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus
Authors: Klaeschen Anna Sophie , Wolf Dominik , Brossart Peter , Bieber Thomas , Wenzel Joerg
Published: November 2016

This study was stimulated by the clinical observation of a rapid response of a chilblain lupus patient to treatment with JAK1/2‐kinase inhibitor ruxolitinib. We investigated the in vivo expression of phospho‐JAK2 in CLE skin samples as well as the immunomodulatory in vitro effect of ruxolitinib in cultured immortalized keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate that ruxolitinib significantly decreases the production of CLE‐typical cytokines (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in patients with CLE and related autoimmune skin diseases.
Interleukin (IL)‐6 modulates transforming growth factor‐β receptor I and II (TGF‐βRI and II) function in epidermal keratinocytes
Authors: Luckett‐Chastain Lerin R. , Cottrell Mackenzie L. , Kawar Bethany M. , Ihnat Michael A. , Gallucci Randle M.
Published: November 2016

It been shown that IL‐6 modulates TGF‐β1 expression in fibroblasts, however, what role IL‐6 plays concerning TGF‐βR expression and function in skin is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL‐6 might modulates TGF‐β receptors in skin. Skin from WT, IL‐6 over‐expressing mice and IL‐6 treated keratinocyte cultures was analysed for TGF‐βRI and TGF‐βRII expression via histology, PCR and flow cytometry. Receptor function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation assays, and Smad7 expression and Smad2/3 phosphorylation. Receptor localization within the membrane was determined by co‐immunoprecipitation. IL‐6 overexpression and treatment increased TGF‐βRII expression in the epidermis. IL‐6 treatment of keratinocytes induced TGF‐βRI and II expression and augmented TGF‐β1‐induced function as demonstrated through increased migration and decreased proliferation. Additionally, IL‐6 treatment of keratinocytes altered receptor activity as indicated by altered Smad2/3 phosphorylation and increased Smad7 and membrane localization. These results suggest that IL‐6 regulates keratinocyte function by modulating TGF‐βRI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.
The biomarker landscape in mycosis fungoides and Sézary syndrome
Authors: Dulmage Brittany , Geskin Larisa , Guitart Joan , Akilov Oleg E.
Published: November 2016

The practice of pre‐emptive individualized medicine is predicated on the discovery, development and application of biomarkers in specific clinical settings. Mycosis fungoides and Sézary syndrome are the two most common type of cutaneous T‐cell lymphoma, yet diagnosis, prognosis and disease monitoring remain a challenge. In this review, we discuss the current state of biomarker discovery in mycosis fungoides and Sézary syndrome, highlighting the most promising molecules in different compartments. Further, we emphasize the need for continued multicentre efforts to validate available and new biomarkers and to develop prospective combinatorial panels of already discovered molecules.
Synergistic effects of polydatin and vitamin C in inhibiting cardiotoxicity induced by doxorubicin in rats
Authors: Wang Hui‐Lin , Cui Xiao‐Hua , Yu Hai‐Lun , Wu Rong , Xu Xu , Gao Jian‐Ping
Published: November 2016

The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of superoxide dismutase (SOD) and the heart rate, attenuate myocardial pathological damage, decrease malondialdehyde (MDA) content, slightly increase arterial pressure and glutathione peroxidase (GSH‐Px) activity, reduce intervals of QRS, QT, and ST, and lower free fatty acid (FFA) content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH‐Px,T‐SOD, Na+K+‐ATPase, and Ca2+Mg2+‐ATPase, elevate phosphocreatine (PCr) and adenosine triphosphate (ATP) contents, slightly increase adenosine diphosphate (ADP) and total adenine nucleotide (TAN) contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group. Meanwhile, the improvement effects on FFA content, the activities of ATPase and SOD, and contents of ATP and TAN in combination group were more obvious than those in polydatin group, and the improvement effects on arterial pressure, heart rate, interval of QRS, GSH‐Px activity, and MDA, ADP, and PCr contents in combination group were slightly obvious when compared with those in polydatin group. In addition, the mRNA expression levels of AMPK‐α2 and PPAR‐α were slightly improved in combination group. The results illustrate that the combination of polydatin and vitamin C has the ability to enhance the myocardial protective effects by its antioxidative effect and improve energy metabolism.
Radon Predictions withGeographical Information SystemCovariates: From Spatial Sampling to Modeling
Authors: De Iaco Sandra , Maggio Sabrina , Palma Monica
Published: November 2016

Radon (Rn) is a potentially toxic gas in soil which may affect human health. Assessing Rn levels in soil gas usually requires enormous efforts in terms of time and costs, since the sampling protocol is very complex. In most cases, the variable under study is sparsely sampled over the domain and this could affect the reliability of the spatial predictions. For this reason, it is useful to incorporate, into the estimation procedure, some auxiliary variables, correlated with the in soil gas Rn concentrations (primary variable) and more densely available over the domain. On the basis of this latter aspect, it is even better if the covariates are derived from a geographical information system (GIS). In this article, the Rn sampling protocol used during a measurement campaign planned over a risk area is described and the process of deriving GIS covariates considered as secondary information for predicting the primary variable is clarified. Then, multivariate modeling and prediction of the Rn concentrations over the domain of interest are discussed and a comparative study regarding the performance of the prediction procedures is presented. Rn prone areas are also analyzed with respect to urban and school density. All these aspects can clearly support decisions on environmental and human safeguard.
SMARCE1 mutation screening in classification of clear cell meningiomas
Authors: Smith Miriam J , Ahn Soomin , Lee Jung‐Il , Bulman Michael , Plessis Daniel du , Suh Yeon‐Lim
Published: November 2016

Aims

Clear cell meningioma (CCM) is a rare subtype of meningioma and shows not only unusual histology, but also unique clinical features. Recently, SMARCE1 mutations have been shown to cause spinal and cranial CCMs. We present 12 cases which were diagnosed with CCM in a single institution between 1997 and 2014, and investigate their SMARCE1 mutation status.

Methods and results

To investigate the SMARCE1 mutation status of these tumours, we used a combination of Sanger sequencing and multiplex ligation‐dependent probe amplification analysis and also performed SMARCE1 immunohistochemical staining. We found both SMARCE1 mutational hits, including novel SMARCE1 mutations, in six of eight tested patients. Immunohistochemical analysis showed loss of SMARCE1 protein staining in all but two cases. Two individuals who were diagnosed originally with CCM were negative for SMARCE1 mutations, but tested positive for NF2 mutations. As a result, these two tumours were re‐analysed and eventually reclassified, as a microcystic and a mixed pattern of meningothelial meningioma with focal clear cell areas, respectively.

Conclusions

These results expand the spectrum of pathogenic variants in SMARCE1 and show that mutation screening can help to facilitate meningioma classification. This may have implications for prognosis and future clinical management of patients, as CCMs are classed as grade II tumours, while microcystic and meningothelial meningiomas are classed as grade I.
Does chemical preconditioning contribute to the effectiveness of scaling and root planing? An in vitro pilot investigation
Authors: Becker M , Ciupka J , Pierchalla T , Fischer KR , Friedmann A
Published: November 2016

Objectives

A solution based on hypochlorite and amino acids was introduced to improve cleaning efficacy on the root surfaces. The purpose of this in vitro pilot study was to evaluate the time reduction and number of strokes required to clean untreated root surfaces in vitro.

Methods

Sixty extracted human teeth displaying areas with subgingival calculus were assigned equally to one of three treatment groups (n = 20) according to the size of occupied areas, estimated by the number of pixels. The groups were assigned to either 30 s penetration time (I) or 300 s (II) or no pretreatment application (III). The weight for instrumentation was calibrated for a M25A curette (Deppeler/Switzerland) with 500 g. A new set of tools was used for each group, and each instrument was sharpened after single use by an EasySharp Device (Deppeler/Switzerland).

Results

The time (in seconds) for instrumentation was recorded as follows: Group I: 32/23.5/50 (median/first quartile/third quartile); group II: 33/20/52.5; group III: 46.5/35.5/52.3. The results for the numbers of strokes were: Group I: 18/14.3/28; group II: 18.5/13/30.5; group III: 17.5/15/25. No statistically significant differences (P < 0.05) were found between the three groups for the variables ‘time’ and ‘number of strokes’.

Conclusions

Within the limits of this in vitro pilot study, preconditioning of the calculus on root surfaces with an alkaline solution failed to reduce the number of strokes and time of instrumentation significantly.
A Tutorial on Palm Distributions for Spatial Point Processes
Authors: Coeurjolly Jean‐François , Møller Jesper , Waagepetersen Rasmus
Published: November 2016

This tutorial provides an introduction to Palm distributions for spatial point processes. Initially, in the context of finite point processes, we give an explicit definition of Palm distributions in terms of their density functions. Then we review Palm distributions in the general case. Finally, we discuss some examples of Palm distributions for specific models and some applications.
Friendships and Intimate Relationships among People with Intellectual Disabilities: A Thematic Synthesis
Authors: Fulford Casey , Cobigo Virginie
Published: November 2016

Background

The purpose of this thematic synthesis was to review qualitative studies on perspectives of persons with intellectual disabilities regarding friendships and intimate relationships.

Materials and methods

A literature search was conducted, including studies published between 2004 and 2014, involving participants 14 years of age or older, who had intellectual disabilities, and participated in focus groups or interviews.

Results

Eighteen studies were included. Three master themes were identified: (i) How do I know someone is my friend? (ii) How do I know someone is my boyfriend or girlfriend? and (iii) What helps and hinders relationships?

Conclusions

Understanding how people with intellectual disabilities describe relationships, and being aware of factors that support and impede relationships, will aid stakeholders in developing training, policies, programmes and services. Knowledge translation of research that focuses on strategies aimed at supporting relationships is crucial to affect change in applied settings and improve quality of life for persons with intellectual disabilities.
Different effect of testosterone and oestrogen on urinary excretion of metformin via regulating OCTs and MATEs expression in the kidney of mice
Authors: He Rui , Ai Ligen , Zhang Dandan , Wan Lili , Zheng Taishan , Yin Jun , Lu Huijuan , Lu Junxi , Lu Fengdi , Liu Fang , Jia Weiping
Published: November 2016

The aim of this study was to investigate the effect of testosterone and oestrogen on regulating organic cation transporters (Octs) and multidrug and toxin extrusions (Mates) expression in the kidney of mice and urinary excretion of metformin. 8 week‐old male db/db mice were treated with estradiol (5 mg/kg), testosterone (50 mg/kg) or olive oil with same volume. Metformin (150 mg/kg) was injected in daily for successive 7 days. Plasma, urine and tissue concentrations of metformin were determined by liquid chromatography‐tandem mass spectrometry (LCMS) assay. Western blotting and Real‐time PCR analysis were successively used to evaluate the renal protein and mRNA expression of Octs and MATEs. After treatment, the protein expression of Mate1 and Oct2 in testosterone group was significantly increased than those in control group (both P < 0.05). The protein expression of Mate1 and Oct2 in estradiol group was significantly reduced by 29.4% and 43.3%, respectively, compared to those in control group (all P < 0.05). These data showed a good agreement with the change in mRNA level (all P < 0.05). The plasma metformin concentration (ng/ml) in mice treated with estradiol was significantly higher than control and testosterone group (677.56 ± 72.49 versus 293.92 ± 83.27 and 261.46 ± 79.45; P < 0.01). Moreover, testosterone increased the metformin urine excretion of mice while estradiol decreasing (both P < 0.01). Spearman correlation analysis showed that gonadal hormone was closely associated with Mate1 and Oct2 expression and metformin urine excretion in db/db mice (all P < 0.05). Testosterone and oestrogen exerted reverse effect on metformin urinary excretion via regulating Octs and Mates expression in the kidney of mice.
A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis
Authors: Wu Yuan , Hu Pengzhi , Xu Hongbo , Yuan Jinzhong , Yuan Lamei , Xiong Wei , Deng Xiong , Deng Hao
Published: November 2016

Focal segmental glomerulosclerosis (FSGS) is the most common glomerular histological lesion associated with high‐grade proteinuria and end‐stage renal disease. Histologically, FSGS is characterized by focal segmental sclerosis with foot process effacement. The aim of this study was to identify the disease‐causing mutation in a four‐generation Chinese family with FSGS. A novel missense mutation, c.1856G>A (p.Gly619Asp), in the collagen type IV alpha‐4 gene (COL4A4) was identified in six patients and it co‐segregated with the disease in this family. The variant is predicted to be disease‐causing and results in collagen IV abnormalities. Our finding broadens mutation spectrum of the COL4A4 gene and extends the phenotypic spectrum of collagen IV nephropathies. Our study suggests that exome sequencing is a cost‐effective and efficient approach for identification of disease‐causing mutations in phenotypically complex or equivocal disorders. Timely screening for COL4A3/COL4A4 mutations in patients with familial FSGS may help both accurately diagnose and treat these patients.
Effects of the Roasting Process Over the Content of Secondary Metabolites from Peanut Grains (Arachis hypogaea. L) with Different Colorations of Testa
Authors: Ferreira Cristiano Dietrich , Ziegler Valmor , Bubolz Vanessa Kern , Da Silva Jennifer , Cardozo Michele Maciel Crizel , Elias Moacir Cardoso , De Oliveira Mauricio
Published: November 2016

Peanut grains are source of proteins and lipids in food and generally consumed after the roasting process. This study focused on: (1) the evaluation of the content of the soluble and insoluble phenolic compounds and flavonoids, total anthocyanin and tocopherols and (2) the relationship of these compounds with the antioxidant activity (ABTS) in peanut grains with different colorations of testa (red, rose, striped and black), subject to the roasting process in an hot air oven and a microwave oven. Increases in the content of soluble phenolics along with reductions in insoluble phenolics, total anthocyanins and tocopherol were observed, without much interference in the antioxidant capacity (ABTS). The highest antioxidant capacity was found in the samples that initially had the highest soluble phenolic compounds. Although the roasting induced a release of insoluble phenolics, transforming them into soluble compounds, this change was not able to alter the antioxidant capacity of the peanuts.

Practical Applications

The roasting is the main method used in the pre‐consumption of peanuts, providing several chemical and structural modifications due to the high temperatures used in this process. It is important to have the knowledge about changes promoted in the metabolic profile of peanut grains subjected to roasting process in microwave oven (more fast) and hot air oven (more slow), because these compounds have several important functions in the human body. With this study we observed three main answers: (1) roasting degrade the total phenolic compounds (soluble + insoluble) in most treatments; (2) the complexed phenolic compounds were more soluble after roasting the peanut grains; and (3) the roasting process in the microwave oven is faster and promote greater release of the metabolites insoluble to the soluble phase, when compared to roasted in oven.
Changes in Drug Use and Polypharmacy After the Age of 90: A Longitudinal Study of the Danish 1905 Cohort
Authors: Wastesson Jonas W. , Oksuzyan Anna , von Bornemann Hjelmborg Jacob , Christensen Kaare
Published: November 2016

Objectives

To determine the longitudinal development of drug use in very old adults.

Design

Longitudinal cohort study with waves in 1998, 2000, 2002, and 2005.

Setting

Nationwide study in Denmark.

Participants

All living Danes born in 1905 were approached in 1998; 2,262 responded at baseline.

Measurements

Self‐reported use of regularly taken drugs. Mean and median number of drugs and growth curve models were used to identify the change in number of drugs as the cohort aged from 92 to 100.

Results

The within‐person use of drugs increased with age for women (0.19 per year; 95% confidence interval (CI) = 0.15–0.24) and men (0.15 per year; 95% CI = 0.06–0.24). Persons leaving the study prematurely had higher baseline values and a steeper increase in their annual use of drugs. The population‐level mean number of drugs increased from baseline (3.6 drugs) to the first follow‐up (4.1 drugs) but thereafter remained stable at approximately 4 drugs. Women used more drugs than men at all waves.

Conclusion

In this first longitudinal study of drug use in nonagenarians, individuals used an increasing number of drugs as they aged. This increase is difficult to detect in cross‐sectional analyses of the population‐level mean. More efforts to understand what is reasonable prescribing at these older ages are needed.
High‐Risk Medications in Hospitalized Elderly Adults: Are We Making It Easy to Do the Wrong Thing?
Authors: Blachman Nina L. , Leipzig Rosanne M. , Mazumdar Madhu , Poeran Jashvant
Published: November 2016

Objectives

To examine dosages of high‐risk medications administered to elderly adults who fall in the hospital and to determine whether electronic default doses are appropriate for elderly adults.

Design

Retrospective.

Setting

Large urban academic hospital.

Participants

Individuals aged 65 and older experiencing a fall.

Measurements

Prescribed daily dosages and use of high‐risk medications (opiates, benzodiazepines, benzodiazepine‐receptor agonists (BRAs), sleep medications, muscle relaxants, antipsychotics) administered within 24 hours before a fall were ascertained and compared with published recommended dosages for older adults and the hospital's electronic medical record (EMR) default doses for these drugs.

Results

Of 328 falls, 62% occurred in individuals administered at least one high‐risk medication within the 24 hours before the fall, with 16% of the falls involving individuals receiving two, and another 16% in individuals receiving three or more. High‐risk medications were often administered at higher‐than‐recommended geriatric daily doses, in particular benzodiazepines and BRAs, for which the dose was higher than recommended in 29 of 51 cases (57%). Hospital EMR default doses were higher than recommended for 41% (12/29) of medications examined.

Conclusion

High‐risk medications were administered to older fallers. Doses administered and EMR default doses were often higher than recommended. Decreasing EMR default doses for individuals aged 65 and older and warnings about the cumulative numbers of high‐risk medications prescribed per person may be simple interventions that could decrease inpatient falls.