bluuebunny/crossref_metadata_2025 huggingface dataset:
Elephant damage, not fire or rainfall, explains mortality of overstorey trees in Serengeti
Authors: Morrison Thomas A. , Holdo Ricardo M. , Anderson T. Michael
Published: November 2015

Generalizations about the drivers of tree demography in tropical savannas continue to prove difficult because of the complex and dynamic interactions involved, and because multi‐year data sets spanning meaningful gradients in potential drivers are lacking.

Overstorey trees play disproportionate roles in the long‐term dynamics and functioning of savanna ecosystems. Understanding demographic patterns in these trees is complicated by their resprouting ability after being top‐killed and few studies have attempted to separate top‐kill from true mortality events.

We examined the interactive effects of fire frequency, mean annual precipitation and elephant herbivory on overstorey (>2 m) tree mortality between 2009 and 2014 across 32 permanent vegetation plots in the Serengeti Ecosystem, Tanzania.

Mean tree mortality over the study period was 0.28 ± 0.02 (0.07 year−1). Among trees that were top‐killed (19.1% of all individuals), 31.2% resprouted. Mortality was driven largely by elephant herbivory, though mortality rates varied considerably across space and tree species. Fire frequency and mean annual rainfall were weak predictors of tree mortality. Over the 5 year period, chronic elephant herbivory (i.e. repeated through time) was a stronger predictor of tree mortality than maximum elephant herbivory, suggesting that repeated, low‐intensity damage from elephants was more important to mortality than acute, but infrequent, damage.

Elephants disproportionately damaged certain tree species relative to their availability on the landscape, and the tolerance to damage differed by species as well. Acacia senegal was strongly selected and appeared to have low tolerance to damage when it occurred, resulting in a mortality rate of 0.736 ± 0.052 (0.234 year−1) over the study period. Top‐killing and resprouting rates varied across species, with Acacias generally having low resprout rates.

Synthesis. Our study highlights the considerable role that chronic herbivory plays in structuring savanna tree populations, irrespective of prevailing fire and rainfall conditions, and provides important vegetative context to the dramatic recent declines and (in the case of Serengeti) increases in savanna elephant densities in sub‐Saharan Africa.
Public Service and Commercial Broadcasting: Impacts on Politics and Society
Authors: Newton Ken
Published: November 2015

This article provides an accessible overview of the growing research literature on the impact of public service and commercial broadcasting and highlights its main implications for policy discussions about the future of public service broadcasting in Western societies. It shows that the populations of countries with public service broad‐ and narrowcasting are better informed about government and politics, are more trusting of other people, have more positive civic attitudes, have greater confidence in democratic institutions and are more likely to engage in democratic politics. Moreover, levels of social trust are higher in countries which have a significant public service element in their media systems, even among individuals who do not habitually watch public TV channels. The article ends with a brief discussion of the implications of this research for the future of public broadcasting in the Western world.
Temperature and Time of Steeping Affect the Antioxidant Properties of White, Green, and Black Tea Infusions
Authors: Hajiaghaalipour Fatemeh , Sanusi Junedah , Kanthimathi M. S.
Published: November 2015

Tea (Camellia sinensis) is the most highly consumed beverage in the world next to water. The common way of preparation is steeping in hot water which is varying for different type of tea. We investigated the antioxidant properties of 6 type of tea leaves under different time and temperatures of extraction method used. In general, all samples tested in this study demonstrated high levels of antioxidant capacity and antioxidant activity. The results indicate that the antioxidants activity is significantly affected by time and temperature of steeping and the highest was depending on the variety. White state values, green and black teas showed different levels of antioxidants under different extraction conditions. Overall, the highest activity for white tea was in prolonged hot and in some assays prolonged hot and cold extracts, whereas for green tea the highest activity observed in prolonged cold steeping while, for black tea was in short hot water infusion. The results of this study showed the antioxidant capacity of white and green tea was greater than black tea.
Resveratrol Regulates Activated Hepatic Stellate Cells by Modulating NF‐κB and the PI3K/Akt Signaling Pathway
Authors: Zhang De‐Quan , Sun Peng , Jin Quan , Li Xia , Zhang Yu , Zhang Yu‐Jing , Wu Yan‐Ling , Nan Ji‐Xing , Lian Li‐Hua
Published: November 2015

In the present study, we investigated whether resveratrol could suppress the hepatic fibrogenesis in activated hepatic stellate cells. The immortalized rat hepatic stellate cells, t‐HSC/Cl‐6, were treated with resveratrol 1 h prior to lipopolysaccharide (LPS, 1 μg/mL). Resveratrol decreased t‐HSC/Cl‐6 cell viability at much lower concentrations within 24 h. Resveratrol pretreatment also decreased the LPS‐induced protein expression of α‐SMA and collagen I. In addition, resveratrol significantly reduced the protein expression of Toll‐like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88), and the expression of phosphorylated phosphatidylinositol 3‐kinase (PI3K) and phosphorylated serine/threonine kinase B (Akt). Moreover, resveratrol markedly blocked the translocation of nuclear factor (NF)‐κB in LPS‐activated HSCs. Furthermore, resveratrol inhibited HSCs activation through stimulating LXRβ, but did not influence LXRα. Overall, we conclude that the antifibrotic effect of resveratrol is the result of blocking NF‐κB activation and PI3K/Akt phosphorylation, which inhibits HSC activation to obstruct liver fibrosis. Thus, resveratrol may be a natural agent for preventing hepatic fibrosis.
Lower rates of hypoglycemia during maintenance treatment with insulin degludec/insulin aspart versus biphasic insulin aspart 30: a combined analysis of two Phase 3a studies in type 2 diabetes
Authors: Christiansen Jens Sandahl , Niskanen Leo , Rasmussen Søren , Johansen Thue , Fulcher Greg
Published: November 2015

Background

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid‐acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30).

Methods

Hypoglycemia data were analyzed from two similarly designed randomized controlled open‐label treat‐to‐target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal.

Results

Over 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between‐treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; −31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; −62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; −84%; P = 0.0061), respectively.

Conclusions

Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.
Incidence rate of lung cancer in urban Shijiazhuang in 2012 with prevention implication
Authors: Wen Denggui , Li Shumei , Zhang Min , Zhang Nan , Wen Xiaoduo , Yang Yi , Fen Cheng , Wang Shijie , Shan Baoen
Published: November 2015

Background

Pollution has been established as an environmental factor in the development of lung cancer; however, the incidence rate in Shijiazhuang, one of China's most heavily polluted cities, is unknown.

Methods

As Chinese citizens are entitled to complete public medical insurance coverage, we estimated the lung cancer incidence rate among registered citizens of urban Shijiazhuang in 2012 using reimbursement records of first hospitalization.

Results

In Shijiazhuang, lung cancer was the most common cancer in men and the second most common cancer in women. The age standardized world incidence rate (ASRW) was 46.42 and 19.14/100 000, respectively, compared with 51.05 and 22.24/100 000, respectively, reported for 63 Chinese tumor registration cities in 2010 (the national level). However, age‐specific rates for the 55–70 range in men and the 25–55 range in women were higher in Shijiazhuang than nationally. Compared with GLOBOCAN 2012 data, the lung cancer ASRW in Shijiazhuang was comparable to that of all industrialized countries (44.7 and 19.6/100 000), but higher than all developing countries (30.0 and 11.1/100 000), Japan (38.8 and 12.9/100 000), and Korea (45.5 and 16.2/100 000).

Conclusion

The lung cancer incidence rate in Shijiazhuang matched the world's highest level in 2012. According to the experience of western countries, the incidence rate in China is expected to continue to rise over the next 40 years. Intervention is urgently required in order to reduce smoking prevalence by a third by 2025 and to take concrete legal action to reduce air pollution.
Chaperone patterns in vernal keratoconjunctivitis are distinctive of cell and Hsp type and are modified by inflammatory stimuli
Authors: Leonardi A. , Tarricone E. , Corrao S. , Alaibac M. , Corso A. J. , Zavan B. , Venier P. , Conway de Macario E. , Macario A. J. L. , Di Stefano A. , Cappello F. , Brun P.
Published: November 2015

Background

Vernal keratoconjunctivitis (VKC) is a severe ocular allergy with pathogenic mechanism poorly understood and no efficacious treatment. The aims of the study were to determine quantities and distribution of Hsp chaperones in the conjunctiva of VKC patients and assess their levels in conjunctival epithelial and fibroblast cultures exposed to inflammatory stimuli.

Methods

Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, Hsp105, and Hsp110 were determined in conjunctiva biopsies from nine patients and nine healthy age‐matched normal subjects, using immunomorphology and qPCR. Conjunctival epithelial cells and fibroblasts were cultured and stimulated with IL‐1β, histamine, IL‐4, TNF‐α, or UV‐B irradiation, and changes in Hsp levels were determined by Western blotting.

Results

Hsp27, Hsp40, Hsp70, and Hsp90 levels increased in the patients' conjunctiva, whereas Hsp10, Hsp60, Hsp100, and Hsp105 did not. Double immunofluorescence demonstrated colocalization of Hsp27, Hsp40, Hsp70, and Hsp90 with CD68 and tryptase. Testing of cultured conjunctival cells revealed an increase in the levels of Hsp27 in fibroblasts stimulated with IL‐4; Hsp40 in epithelial cells stimulated with IL‐4 and TNF‐α and in fibroblasts stimulated with IL‐4, TNF‐α, and IL‐1β; Hsp70 in epithelial cells stimulated with histamine and IL‐4; and Hsp90 in fibroblasts stimulated with IL‐1β, TNF‐α, and IL‐4. UV‐B did not induce changes.

Conclusions

VKC conjunctiva displays distinctive quantitative patterns of Hsps as compared with healthy controls. Cultured conjunctival cells respond to cytokines and inflammatory stimuli with changes in the Hsps quantitative patterns. The data suggest that interaction between the chaperoning and the immune systems drives disease progression.
Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo‐controlled study
Authors: Melehan K. L. , Hoyos C. M. , Yee B. J. , Wong K. K. , Buchanan P. R. , Grunstein R. R. , Liu P. Y.
Published: November 2015

Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre‐specified at 8, 11 and 13 nmol/L. This was a randomized placebo‐controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep‐related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep‐related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing.
Laying open (deroofing) and curettage of sinus as treatment of pilonidal disease: a systematic review and meta‐analysis
Authors: Garg Pankaj , Menon Geetha R. , Gupta Vikas
Published: November 2015

Background

Laying open (deroofing, not excision) and curettage of the sinus is a minimally invasive procedure to treat pilonidal disease. A consensus on its efficacy and outcomes has not been reached. We reviewed and meta‐analysed the efficacy of this procedure.

Methods

PubMed, Medline, Scopus, Ovid, Cochrane central register of controlled trials (CENTRAL) and Google scholar databases were searched. All studies describing laying open (not excision) of sinus with curettage of the tract to treat pilonidal disease (simple and complicated) were included. The primary outcome parameter was recurrence and the secondary outcome parameters were complication rate, operating time, return to work and healing time.

Results

A total of 1194 studies were screened. Out of these, 13 studies were finally included for the analysis. The analysis (n = 1445) demonstrated a net proportion meta‐analysis (random effect) pooled rate of 4.47% (95% CI = 0.029–0.063) for recurrence, 1.44% (95% CI = 0.005–0.028) for complications, 34.59 min (95% CI = 13.58–55.61) for operating time, 21–72 days for healing time and 8.4 days (95% CI = 5.23–11.72) for return to work. The procedure was possible under local anaesthesia in seven out of 13 studies.

Conclusions

The meta‐analysis demonstrates that laying open (deroofing) and curettage has distinct advantages. These are high success rate, possible in all types of pilonidal disease (simple and complex), low complication rate, short operating time and early return to normal routine and work. This procedure can be conveniently under local anaesthesia as an outpatient procedure.
Enhanced recovery pathways in abdominal gynecologic surgery: a systematic review and meta‐analysis
Authors: de Groot Jeanny J.A. , Ament Stephanie M.C. , Maessen José M.C. , Dejong Cornelis H.C. , Kleijnen Jos M.P. , Slangen Brigitte F.M.
Published: November 2015

Introduction

Enhanced recovery pathways have been widely accepted and implemented for different types of surgery. Their overall effect in abdominal gynecologic surgery is still underdetermined. A systematic review and meta‐analysis were performed to provide an overview of current evidence and to examine their effect on postoperative outcomes in women undergoing open gynecologic surgery.

Material and methods

Searches were conducted using Embase, Medline, CINAHL, and the Cochrane Library up to 27 June 2014. Reference lists were screened to identify additional studies. Studies were included if at least four individual items of an enhanced recovery pathway were described. Outcomes included length of hospital stay, complication rates, readmissions, and mortality. Quantitative analysis was limited to comparative studies. Effect sizes were presented as relative risks or as mean differences (MD) with 95% confidence intervals (CI).

Results

Thirty‐one records, involving 16 observational studies, were included. Diversity in reported elements within studies was observed. Preoperative education, early oral intake, and early mobilization were included in all pathways. Five studies, with a high risk of bias, were eligible for quantitative analysis. Enhanced recovery pathways reduced primary (MD −1.57 days, 95% CI CI −2.94 to −0.20) and total (MD −3.05 days, 95% CI −4.87 to −1.23) length of hospital stay compared with traditional perioperative care, without an increase in complications, mortality or readmission rates.

Conclusion

The available evidence based on a broad range of non‐randomized studies at high risk of bias suggests that enhanced recovery pathways may reduce length of postoperative hospital stay in abdominal gynecologic surgery.
New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs
Authors: Ignácio Zuleide M. , Réus Gislaine Z. , Arent Camila O. , Abelaira Helena M. , Pitcher Meagan R. , Quevedo João
Published: November 2015

Despite the revolution in recent decades regarding monoamine involvement in the management of major depressive disorder (MDD), the biological mechanisms underlying this psychiatric disorder are still poorly understood. Currently available treatments require long time courses to establish antidepressant response and a significant percentage of people are refractory to single drug or combination drug treatment. These issues, and recent findings demonstrating the involvement of synaptic plasticity in the pathophysiological mechanisms of MDD, are encouraging researchers to explore the molecular mechanisms underlying psychiatric disease in more depth. The discovery of the rapid antidepressant effect exerted by glutamatergic and cholinergic agents highlights the mammalian target of rapamycin (mTOR) pathway as a critical pathway that contributes to the efficacy of these pharmacological agents in clinical and pre‐clinical research. The mTOR pathway is a downstream intracellular signal that transmits information after the direct activation of α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA) and neurotrophic factor receptors. Activation of these receptors is hypothesized to be one of the major axes involved in the synthesis of synaptogenic proteins underlying synaptic plasticity and critical to both the rapid and delayed effects exerted by classic antidepressants. This review focuses on the involvement of mTOR in the pathophysiology of depression and on molecular mechanisms involved in the activity of emerging and classic antidepressant agents.
A simultaneous population pharmacokinetic analysis of rifampicin in Malawian adults and children
Authors: Schipani Alessandro , Pertinez Henry , Mlota Rachel , Molyneux Elizabeth , Lopez Nuria , Dzinjalamala Fraction K. , van Oosterhout Joep J. , Ward Steve A. , Khoo Saye , Davies Gerry
Published: November 2015

AIMS

Low rifampicin plasma concentrations can lead to treatment failure and increased risk of developing drug resistant tuberculosis. The objectives of this study were to characterize the population pharmacokinetics (popPK) of rifampicin in Malawian children and adults with tuberculosis, simulate exposures under revised WHO dosing guidelines that aim to reduce the risk of low exposures of rifampicin and examine predicted exposures using weight‐ and age‐based dosing bands under new dosing recommendations.

Methods

Patients were recruited at least two weeks after initiation of the intensive phase of treatment and received RIF in FDC of anti‐TB drugs. A total of 5‐6 rich and 1‐2 sparse samples were collected. nonmem (v7.2) was used to build a population‐PK model.

Results

A 165 TB patients, 115 adults and 50 children, aged 7 months to 65 years and weighing 4.8 to 87 kg, were included in the one compartment model with first order absorption best described the data. The mean population estimate for CL/F was 23.9 (l h–1 70 kg–1) with inter‐individual variability of 46.6%. Exposure was unaffected by HIV status. Relative bioavailability in children was estimated at 49% lower compared to adults (100% relative bioavailability). Simulations showed significantly lower rifampicin exposure in children vs. adults. In children average AUC was 13.5 mg l‐1 h, which was nearly half that was observed in adults (26.3 mg l‐1 h). Using age as a surrogate for weight in dosing bands gave similar results compared with the weight bands. Increasing dose to approximately 15 mg kg–1, increased AUC in children to an average of 22 mgl‐1 h. bringing expected exposures in children closer to those predicted for adults.

Conclusion

The popPK model developed can be used to optimize rifampicin exposures through dosing simulations. WHO dosing recommendations may not be achieved using currently licensed fixed dose combination formulations of TB therapy.
Modelling of the Sedative Effects of Propofol in Patients undergoing Spinal Anaesthesia: A Pharmacodynamic Analysis
Authors: Roh Go Un , Kim Youngsoon , Ha Sang Hee , Jeong Kyu Hee , Choi Sumin , Han Dong Woo
Published: November 2015

Sedation can increase patient comfort during spinal anaesthesia. Understanding the relationship between the propofol effect‐site concentration (Ce) and patient sedation level could help clinicians achieve the desired sedation level with minimal side effects. We aimed to model the relationship between the propofol Ce and adequate and deep sedation and also incorporate covariates. Thirty patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. Propofol was administered via an effect‐site target‐controlled infusion device using the Schnider pharmacokinetic model. The pharmacodynamic models for both adequate sedation [Observer's Assessment of Alertness/Sedation (OAA/S) scores of 3–4] and deep sedation (OAA/S scores of 1–2) were developed using nonlinear mixed‐effects modelling. Increments in the propofol Ce were associated with increased depths of sedation. In the basic model, the estimated population Ce50 values for adequate and deep sedation were 0.94 and 1.52 μg/ml, respectively. The inclusion of the patient's age and sensory block level for adequate sedation and of age for deep sedation as covariates significantly improved the basic model by decreasing the objective function's minimum value from 10696.72 to 10677.92 (p = 0.0003). The simulated Ce50 values for adequate sedation in 20‐year‐old patients with a T12 sensory level and in 80‐year‐old patients with a T4 level were 1.63 and 0.53 μg/ml, respectively. Both age and sensory block level should be considered for adequate sedation, and the propofol concentration should be reduced for elderly patients with a high spinal block to avoid unnecessarily deep levels of sedation.
Containing Brazil: Mexico's Response to the Rise of Brazil
Authors: COVARRUBIAS ANA
Published: November 2015

Historically, relations between Brazil and Mexico have not been particularly close. One of the consequences of Brazil's rise was to draw the two countries together, although not necessarily in a harmonious way. The article argues that Mexican governments resented Brazil's attempts at becoming a global player at a time when they pursued the same goal. Mexico's response to Brazil's international projection was to approach it, trying to contain it, and to avoid exclusion from regional initiatives.
Contemporary Argentina and the Rise of Brazil
Authors: RUSSELL ROBERTO , TOKATLIAN JUAN G.
Published: November 2015

This article focuses on: (a) Argentine elites' perception of Brazil's international rise from 2001/2002 up to the present; and (b) the three strategic options implemented by Argentina as a response to Brazil's growing power and influence. These options – regionalism, light balancing and soft hedging – constitute a new typology, since the corresponding behaviors cannot be inscribed within the conventional logic of balancing or bandwagoning. The article concludes with brief comments on what could be seen as a new stage in bilateral relations.
Brazil: What Rise of What Power?
Authors: GARDINI GIAN LUCA
Published: November 2015

From 2003, the Lula administration has started a discourse and a practice of Brazil as a major international player. However, the conversion of a giant economy and political activism into regional and global power status has eluded Brazil so far. Labels such as great power or leader do not fit it. This article suggests that the problem is not with Brazil being unable to tick all the boxes but with the definitions that we use. Hence a call for new mental categories that better capture the surge of Brazil and other emerging powers in the twenty‐first century. Drawing from the business literature, Brazil can be better understood as an international manager.
Chemical RNA Editing for Genetic Restoration: The Relationship between the Structure and Deamination Efficiency of Carboxyvinyldeoxyuridine Oligodeoxynucleotides
Authors: Vu Luyen Thi , Nguyen Thanh Thi Kim , Md Thoufic Azad Anam , Suzuki Hitoshi , Tsukahara Toshifumi
Published: November 2015

Oligodeoxynucleotides containing 5‐carboxyvinyl‐2ʹ‐deoxyuridine (CVU‐containing ODNs) for successful site‐specific transition of cytosine to uridine by photo‐cross‐linking have three parts: the complementary sequence, hairpin loop and the 5ʹ‐terminal photoresponsive nucleobase CVU. Photo‐cross‐linking with CVU‐containing ODNs was performed using UV (366 nm) irradiation, followed by heat treatment for deamination. The cross‐linked nucleotide was cleaved by photosplitting (UV, 312 nm). The products were analyzed using restriction fragment length polymorphism and fluorescence measurements. In previous studies, we have successfully performed site‐directed photochemical base substitution toward a synthetic single‐stranded 100‐mer ODN target (ss100‐nt) and in vitro‐synthesized full‐length blue fluorescent protein mRNA as targets. Although the efficiency of C‐to‐U site‐specific transition strongly depends on the sequence and structure of CVU‐containing ODNs, the relationship between CVU‐containing ODNs and the deamination efficiency of targeted editing remains unclear. Therefore, in this study, we attempted to identify the optimal sequence and primary structure of CVU‐containing ODNs for site‐directed specific transition. To evaluate the structure–deamination efficiency relationship, a series of eight CVU‐containing ODNs were designed and studied. We showed that the optimal deamination efficiency was achieved with ODNs having a complementary sequence length slightly more than 14 nt and a hairpin length of 9 nt.
Refining the head and neck cancer referral guidelines: a two‐centre analysis of 4715 referrals
Authors: Tikka T. , Pracy P. , Paleri V.
Published: November 2015

Objectives

To identify the set of referral criteria that will offer optimal diagnostic efficacy in patients suspected to have head and neck cancer (HNC) in the primary care setting.

Design

Statistical analysis of referral criteria and outcomes.

Setting

Two tertiary care cancer centres in the United Kingdom.

Participants

4715 patients who were referred via the fast‐track system with a suspected HNC between 2007 and 2010.

Main outcome measures

Parameters of diagnostic efficacy, multivariate regression model to calculate estimated probability of HNC and area under the receiver operating characteristic curve (AUROC).

Results

The majority of referring symptoms had a positive predictive value higher than the 3% cut‐off point stated to be significant for HNC detection in the 2015 NICE recommendations. Nevertheless, our multivariate analysis identified nine symptoms to be linked with HNC. Of these, only four are included in the latest NICE guidelines. The best fit predictive model for this data set included the following symptoms: hoarseness >3 weeks, dysphagia >3 weeks, odynophagia, unexplained neck mass, oral swelling >3 weeks, oral ulcer >3 weeks, prolonged otalgia with normal otoscopy, the presence of blood in mouth with concurrent sensation of lump in throat and the presence of otalgia with concurrent lump in throat sensation. Intermittent hoarseness and sensation of lump in throat were negatively associated with HNC. The AUROC demonstrated that our model had a higher predictive value (0.77) compared to those generated using the NICE 2005 (0.69) and 2015 (0.68) referral criteria (P < 0.0001). An online risk calculator based on this study is available at http://www.orlhealth.com/risk-calculator.html.

Conclusions

This study presents a significantly refined version of referral guidelines which demonstrate greater diagnostic efficacy than the current NICE guidelines. We recommend that further iterative refinements of referral criteria be considered when referring patients with suspected HNC.
The relationship between arterial stiffness and the lifestyle habits of female athletes after retiring from competitive sports: a prospective study
Authors: Koshiba Hiroya , maeshima Estuko , Okumura Yuka
Published: November 2015

This study investigated the relationship between changes in arterial stiffness and the lifestyle habits of endurance athletes after retiring from competition. The subjects were 10 female university endurance athletes. We used formPWV/ABI® as an index for arterial stiffness and measured brachial‐ankle pulse‐wave velocity (baPWV) directly before subjects retired (0Y) and at 2 years after retirement (2Y). Furthermore, to investigate the relationship between arterial stiffness and lifestyle habits 2 years later, Lifecorder ® PLUS was used to measure physical activity levels, hours of sleep were surveyed using a questionnaire, and a food intake survey was conducted using Excel Eiyoukun Food Frequency Questionnaire Based on Food Group, FFQg Ver. 3.5. We found that baPWV increased significantly from 0Y to 2Y (P<0·05). Furthermore, negative correlations were observed between 2Y baPWV and step count as the physical activity index (r = −0·653, P<0·05) and moderate physical activity (r = −0·663, P<0·05). With regard to lifestyle habits that affected the amount of increase in baPWV from 0Y to 2Y (ΔbaPWV), negative correlations were noted between the step count (r = −0·690, P<0·05) and total physical activity (r = −0·657, P<0·05). However, no significant correlations were observed between 2Y baPWV and ΔbaPWV with food intake or hours of sleep. The results of this study suggested that physical activity was a lifestyle habit that inhibited an increase in arterial stiffness after retirement from competition and that having a high step count or engaging in physical activity for long periods of time in particular was useful in this regard.
Pseudosyndactyly – an inflammatory and fibrotic wound healing disorder in recessive dystrophic epidermolysis bullosa
Authors: Breitenbach Jenny , Gruber Christina , Klausegger Alfred , Trost Andrea , Bogner Barbara , Reitsamer Herbert , Bauer Johann W.
Published: November 2015

Background

A genetic blistering skin disease, recessive dystrophic epidermolysis bullosa (RDEB), is marked by severe wound healing defects and finger contractures. The purpose of this investigation was to elucidate the mechanisms of impaired wound healing and pseudosyndactyly occurring in RDEB patients by studying the role of known inflammation and fibrosis markers in RDEB pseudosyndactyly tissue.

Patients and methods

We studied the expression of the fibrosis and/or inflammation markers tenascin‐C, α‐smooth muscle actin, transforming growth factor‐β1, interleukin‐1β, and interleukin‐6 in scarring and nonscarring tissue from healthy donors and RDEB patients by semiquantitative real time‐PCR and, where applicable, by immunoblots. Furthermore, the distribution pattern of α‐smooth muscle actin and tenascin‐C were assessed by immunofluorescence microscopy.

Results

Based on mRNA and protein analysis, we found upregulation of tenascin‐C, interleukin‐1β, and interleukin‐6 – but not of transforming growth factor‐β1 – in recessive dystrophic epidermolysis bullosa scar samples taken from pseudosyndactyly hands. Unexpectedly, α‐smooth muscle actin was not upregulated.

Conclusions

Our results confirm inflammation and fibrosis in recessive dystrophic epidermolysis bullosa, especially in scars, suggesting major roles for these processes in pseudosyndactyly. Our data therefore suggests the potential use of antiinflammatory and antifibrotic drugs in the prevention of pseudosyndactyly.
Die diagnostische Relevanz der direkten Immunfluoreszenz beim okulären Schleimhautpemphigoid
Authors: Mehra Tarun , Guenova Emmanuella , Dechent Frieder , Würth Florian , Zierhut Manfred , Röcken Martin , Schaller Martin , Deuter Christoph
Published: November 2015

Hintergrund und Zielsetzung

Ziel war es, den diagnostischen Wert der direkten Immunfluoreszenz (DIF) beim okulären Schleimhautpemphigoid (okuläres MMP – „mucous membrane pemphigoid“) unter Beachtung der Immunfluoreszenzmuster und der Biopsiestellen zu bestimmen.

Patienten und Methoden

Geprüft wurden DIF‐Ergebnisse und Krankenakten von 54 Patienten mit Verdachtsdiagnose eines okulären MMP.

Ergebnisse

Es gab insgesamt eine Prävalenz des okulären MMP in 70,4 % der Fälle. Lineare Ablagerungen von IgA, IgG oder C3 zeigten einen hohen positiven prädiktiven Wert (84 ‐ 100 %). Der Empfindlichkeitswert und der negative prädiktive Wert von IgG, IgM, IgG und C3 bei DIF waren bei kutanen Proben höher als bei Bindehaut‐Biopsien, und lieferten daher eine höhere diagnostische Genauigkeit. Die Empfindlichkeit der DIF scheint beim okulären MMP geringer zu sein als beim bullösen Pemphigoid.

Schlussfolgerungen

Der diagnostische Wert der DIF bei der Abklärung des okulären MMP wurde bestätigt. Biopsien aus nicht‐konjunktivalem, kutanen Gewebe scheinen jedoch genauere Ergebnisse zu liefern.
Efficacy and safety of a 5‐day regimen of azacitidine for patients with high‐risk myelodysplastic syndromes
Authors: Fujimaki Katsumichi , Miyashita Kazuho , Kawasaki Rika , Tomita Naoto
Published: November 2015

Although a 7‐day (d) regimen of azacitidine (AZA) is the standard treatment of high‐risk myelodysplastic syndromes (MDS), AZA is difficult to administer during weekends in an outpatient setting. We retrospectively investigated the outcome of a 5‐d regimen of AZA in patients with high‐risk MDS. High‐risk MDS was defined as MDS with intermediate‐2‐ or high‐risk MDS according to the International Prognostic Scoring System. Every months AZA was given at 75 mg/m2 per day for 5–7 d in hospital for first cycle and 5 d in outpatient for second cycle and later. Between April 2011 and December 2013, AZA treatment was initiated in 25 patients (men, 22; women, 3; median age, 75 yr; age range, 59–86 yr). The median number of AZA cycles was 10 (range, 1–24). Twenty patients received more than three cycles of AZA and 13 (52%) achieved any hematological improvement (HI). The median time to first response was two cycles (1–3). The most common non‐hematological adverse events were neutropenia in 21 patients and thrombocytopenia in 17 patients. Nineteen patients died. The main cause of death was disease progression (five patients) and infectious complications (11 patients). The median overall survival was 13.2 months. The 5‐d AZA regimen showed a good continuation rate of more than three cycles and an equivalent HI with the 7‐d regimen.
Motion‐induced disturbance of auditory–motor synchronization and its modulation by transcranial direct current stimulation
Authors: Ono Kentaro , Mikami Yusuke , Fukuyama Hidenao , Mima Tatsuya
Published: November 2015

The timing of personal movement with respect to external events has previously been investigated using a synchronized finger‐tapping task with a sequence of auditory or visual stimuli. While visuomotor synchronization is more accurate with moving stimuli than with stationary stimuli, it remains unclear whether the same principle holds true in the auditory domain. Although the right inferior–superior parietal lobe (IPL/SPL), a center of auditory motion processing, is expected to be involved in auditory–motor synchronization with moving sounds, its functional relevance has not yet been investigated. The aim of the present study was thus to clarify whether horizontal auditory motion affects the accuracy of finger‐tapping synchronized with sounds, as well as whether the application of transcranial direct current stimulation (tDCS) to the right IPL/SPL affects this. Nineteen healthy right‐handed participants performed a task in which tapping was synchronized with both stationary sounds and sounds that created apparent horizontal motion. This task was performed before and during anodal, cathodal and sham tDCS application to the right IPL/SPL in separate sessions. The time difference between the onset of the sounds and tapping was larger with apparently moving sounds than with stationary sounds. Cathodal tDCS decreased this difference, anodal tDCS increased the variance of the difference and sham stimulation had no effect. These results supported the hypothesis that auditory motion disturbs efficient auditory–motor synchronization and that the right IPL/SPL plays an important role in tapping in synchrony with moving sounds via auditory motion processing.
Functional dissociation between regularity encoding and deviance detection along the auditory hierarchy
Authors: Aghamolaei Maryam , Zarnowiec Katarzyna , Grimm Sabine , Escera Carles
Published: November 2015

Auditory deviance detection based on regularity encoding appears as one of the basic functional properties of the auditory system. It has traditionally been assessed with the mismatch negativity (MMN) long‐latency component of the auditory evoked potential (AEP). Recent studies have found earlier correlates of deviance detection based on regularity encoding. They occur in humans in the first 50 ms after sound onset, at the level of the middle‐latency response of the AEP, and parallel findings of stimulus‐specific adaptation observed in animal studies. However, the functional relationship between these different levels of regularity encoding and deviance detection along the auditory hierarchy has not yet been clarified. Here we addressed this issue by examining deviant‐related responses at different levels of the auditory hierarchy to stimulus changes varying in their degree of deviation regarding the spatial location of a repeated standard stimulus. Auditory stimuli were presented randomly from five loudspeakers at azimuthal angles of 0°, 12°, 24°, 36° and 48° during oddball and reversed‐oddball conditions. Middle‐latency responses and MMN were measured. Our results revealed that middle‐latency responses were sensitive to deviance but not the degree of deviation, whereas the MMN amplitude increased as a function of deviance magnitude. These findings indicated that acoustic regularity can be encoded at the level of the middle‐latency response but that it takes a higher step in the auditory hierarchy for deviance magnitude to be encoded, thus providing a functional dissociation between regularity encoding and deviance detection along the auditory hierarchy.
Role of c‐Jun N‐terminal kinase in late nerve regeneration monitored by in vivo imaging of thy1‐yellow fluorescent protein transgenic mice
Authors: Tu Nguyen H. , Katano Tayo , Matsumura Shinji , Pham Vuong Minh , Muratani Tadatoshi , Minami Toshiaki , Ito Seiji
Published: November 2015

The restoration of function to injured peripheral nerves separated by a gap requires regeneration across it and reinnervation to target organs. To elucidate these processes, we have established an in vivo monitoring system of nerve regeneration in thy1‐yellow fluorescent protein transgenic mice expressing a fluorescent protein in their nervous system. Here we demonstrated that motor and sensory nerves were regenerated in a coordinated fashion across the gap and that the functional recovery of the response to mechanical stimuli correlated well with sensory innervation to the foot. Among the mitogen‐activated protein kinase inhibitors examined, only the c‐Jun N‐terminal kinase (JNK) inhibitors delayed functional recovery. Although it did not affect the reinnervation of the muscle, the JNK inhibitor delayed sensory nerve innervation to the skin for over 8 weeks and increased the expression of activatng transcription factor 3 (ATF3), a neuronal injury marker, in the dorsal root ganglion over the same time period. Antibodies against nerve growth factor, glia‐derived neurotrophic factor, and brain‐derived neurotrophic factor applied to the transection site delayed the functional recovery in this order of potency. These neurotrophic factors enhanced neurite outgrowth from cultured dorsal root ganglion neurons, and the JNK inhibitor reversed their stimulatory effects. These results suggest that JNK played roles in nerve regeneration at both early and late phases. Taken together, the present study demonstrated that neurotrophic factors released from the distal nerve may accelerate motor and sensory nerve regeneration across the gap in a coordinated fashion and reinnervation of the target organs independently. The model characterized here has the advantage of in vivo monitoring of the evaluation of morphological and functional recovery in the same mice for a long period of time.
Male competition fitness landscapes predict both forward and reverse speciation
Authors: Keagy Jason , Lettieri Liliana , Boughman Janette W.
Published: November 2015

Speciation is facilitated when selection generates a rugged fitness landscape such that populations occupy different peaks separated by valleys. Competition for food resources is a strong ecological force that can generate such divergent selection. However, it is unclear whether intrasexual competition over resources that provide mating opportunities can generate rugged fitness landscapes that foster speciation. Here we use highly variable male F2 hybrids of benthic and limnetic threespine sticklebacks,Gasterosteus aculeatusLinnaeus, 1758, to quantify the male competition fitness landscape. We find that disruptive sexual selection generates two fitness peaks corresponding closely to the male phenotypes of the two parental species, favouring divergence. Most surprisingly, an additional region of high fitness favours novel hybrid phenotypes that correspond to those observed in a recent case of reverse speciation after anthropogenic disturbance. Our results reveal that sexual selection through male competition plays an integral role in both forward and reverse speciation.
Covariance modulates the effect of joint temperature and food variance on ectotherm life‐history traits
Authors: Koussoroplis Apostolos‐Manuel , Wacker Alexander
Published: November 2015

Understanding animal performance in heterogeneous or variable environments is a central question in ecology. We combine modelling and experiments to test how temperature and food availability variance jointly affect life‐history traits of ectotherms. The model predicts that as mean temperatures move away from the ectotherm's thermal optimum, the effect size of joint thermal and food variance should become increasingly sensitive to their covariance. Below the thermal optimum, performance should be positively correlated with food–temperature covariance and the opposite is predicted above it. At lower temperatures, covariance should determine whether food and temperature variance increases or decreases performance compared to constant conditions. Somewhat stronger than predicted, the covariance effect below the thermal optimum was confirmed experimentally on an aquatic ectotherm (Daphnia magna) exposed to diurnal food and temperature variance with different amounts of covariance. Our findings have important implications for understanding ectotherm responses to climate‐driven alterations of thermal mean and variance.
Stoichiometry and deletion analyses of subunits in the heterotrimeric F‐ATP synthase c ring from the acetogenic bacterium Acetobacterium woodii
Authors: Brandt Karsten , Müller Daniel B. , Hoffmann Jan , Langer Julian D. , Brutschy Bernd , Morgner Nina , Müller Volker
Published: November 2015

The ion‐translocating c ring of the Na+ F1Fo ATP synthase of the anaerobic bacterium Acetobacterium woodii is the first heteromeric c ring found in nature that contains one V‐ (c1) and two F‐type‐like c subunits (c2/c3), the latter of identical amino acid sequence. To address whether they are of equal or different importance for function, they were deleted in combination or individually. Deletion of c1 was compensated by incorporation of two c2/c3 subunits but the enzyme was unstable and largely impaired in Na+ transport. Deletion of c2 was compensated by incorporation of c3 but also led to a reduction of Na+ transport. Deletion of c3 had no effect. In contrast, deletion of both c2 and c3 led to a complete loss of ATPase activity at the cytoplasmic membrane. Mass spectrometric analysis of c2+1 Ala and c2+2 Ala variants revealed a copy number of 8 : 1 for c2/c3 which is consistent with the biochemical characteristics of the variants. These data indicate a role of c1 in assembly and a function of c2 as the predominant c ring constituent.
Spatial abundance patterns and recruitment of a virus‐affected commercial mollusc fishery
Authors: Jalali M. A. , Ierodiaconou D. , Gorfine H. , Christiansen F. , Young M.
Published: November 2015

Infectious pathogens figure prominently among those factors threatening marine wildlife. Mass mortality events caused by pathogens can fundamentally alter the structure of wild fish stocks and depress recruitment rates and yield. In the most severe instances, this can precipitate stock collapses resulting in dramatic economic losses to once valuable commercial fisheries. An outbreak of a herpes‐like virus among commercially fished abalone populations in the south‐west fishery of Victoria, Australia, during 2006–2007, has been associated with high mortality rates among all cohorts. Long‐term records from fishery‐independent surveys of blacklip abalone Haliotis rubra (Leach) enabled abundance from pre‐ and post‐viral periods to be analysed to estimate stock density and biomass. The spatial distribution of abundance in relation to physical habitat variables derived from high‐resolution bathymetric LiDAR data was investigated. Significant differences were observed in both measures between pre‐ and post‐viral periods. Although there was some limited evidence of gradual stock improvement in recent years, disease‐affected reefs have remained below productivity rates prior to the disease outbreak suggesting a reduction in larval availability or settlement success. This was corroborated by trends in sublegal sized blacklip abalone abundance that has yet to show substantial recovery post‐disease. Abundance data were modelled as a function of habitat variables using a generalised additive model (GAM) and indicated that high abundance was associated with complex reef structures of coastal waters (<15 m). This study highlights the importance of long‐term surveys to understand abalone recovery following mass mortality and the links between stock abundance and seafloor variability.