bluuebunny/crossref_metadata_2025 huggingface dataset:
The convergence of senescence and nutrient sensing during lymphocyte ageing
Authors: Akbar A N
Published: October 2016

Immunosurveillance requires the migration of lymphocytes and their activation to induce proliferation and effector function. Effective immunity requires an optimal supply of nutrients to lymphocytes. Cells contain nutrient sensing apparatus such as adenosine 5′-monophosphate-activated protein kinase (AMPK) that surveys intracellular ATP levels. Immunity declines during ageing and one possibility is that the energy balance may be altered in old lymphocytes. This paper summarizes recent data identifying a convergence of senescence and nutrient signalling pathways in lymphocytes that inhibit both T cell and natural killer (NK) cell function during ageing. Significantly, these pathways can be inhibited to enhance the activity of these cells.
Parathyroid adenoma: a comprehensive biochemical and histological correlative study
Authors: Stern S. , Mizrachi A. , Strenov Y. , Knaanie A. , Benbassat C. , Shpitzer T. , Bachar G.
Published: October 2016

Objective

To investigate the controversial relationship between preoperative calcium and parathyroid hormone levels and the dimensions and histological features of parathyroid adenoma in patients with primary hyperparathyroidism.

Study design

Historical cohort.

Setting

Tertiary medical centre.

Subjects and methods

Clinical and tumour‐related data were collected from the medical files of all patients who underwent parathyroidectomy for primary hyperparathyroidism in 1996–2012. Preoperative blood parathyroid hormone and calcium levels and urine calcium levels were correlated with the size, weight and volume of the parathyroid adenoma. Pathohistological features were determined in a representative sample of archived paraffin‐embedded sections and analysed by calcium or parathyroid hormone level (high/low) and adenoma weight (high/low).

Results

A total of 378 patients were included. There was a statistically significant direct correlation of preoperative calcium and parathyroid hormone levels with tumour dimensions and of tumour weight and chief‐cell percentage. At a preoperative calcium level >11.5 mg/dL and parathyroid hormone (PTH) level >165 mg/dL, we predict that the adenoma would measure more than 2.7 g, 2.18 cm and volume of 3.59 cm3.

Conclusions

In patients with primary hyperparathyroidism, preoperative calcium and PTH levels may be predictive of parathyroid adenoma dimensions.
Cardiovascular parameters of chest CT scan in estimating pulmonary arterial pressure in patients with pulmonary hypertension
Authors: Li Mengxi , Wang Shouyang , Lin Weiquan , Li Jinhui , Wang Chunyang , Chen Huai , Lu Wenju , Yang Kai , Wang Jian , Zeng Qingsi
Published: October 2016

Objective

To develop a formula to compute mean pulmonary arterial pressure (MPAP) by chest computerized tomography (CT), and to verify its accuracy and reliability.

Methods

Eighty‐five patients who had taken chest CT and right heart catheterization (RHC) were recruited. The pulmonary arterial systolic pressure (PASP), pulmonary arterial diastolic pressure (PADP), and MPAP of each subject were measured and recorded by RHC. The diameters of the ascending aorta (dAA), descending aorta (dDA) and main pulmonary artery (dMPA), Cobb angle, diameters of right ventricle (dRV), diameters of left ventricle (dLV) were measured by means of chest CT scans. Systolic blood pressure (SBP) was measured by using electronic sphygmomanometer. A linear regression equation was generated in 56 patients to estimate PAP based on chest CT values, 29 patients were used to test the accuracy of the formula.

Results

The computed equation for analyzing MPAP is: MPAP = 9.011 + 34.195 × dMPA/dAA − 0.319 × SBP + 0.402 × Cobb angle. AUC of equation with three variables (dMPA/dAA, SBP, and Cobb angle) was 0.923 with 95% CI (0.863‐0.982). The mean ± SD of predicted values and RHC values had no statistical difference.

Conclusions

Ratio of dMAP/dAA, Cobb angle, and SBP can be reliably used to estimate MPAP and predict severity of PH.
Psychological outcomes of evening and night closed‐loop insulin delivery under free living conditions in people with Type 1 diabetes: a 2‐month randomized crossover trial
Authors: Kropff J. , DeJong J. , del Favero S. , Place J. , Messori M. , Coestier B. , Farret A. , Boscari F. , Galasso S. , Avogaro A. , Bruttomesso D. , Cobelli C. , Renard E. , Magni L. , DeVries J. H. ,   the AP@home consortium
Published: October 2016

Aim

To assess the impact on fear of hypoglycaemia and treatment satisfaction with an artificial pancreas system used for 2 consecutive months, as well as participant acceptance of the artificial pancreas system.

Methods

In a randomized crossover trial patient‐related outcomes associated with an evening‐and‐night artificial pancreas and sensor‐augmented pump therapy were compared. Both intervention periods lasted 8 weeks. The artificial pancreas acceptance questionnaire (range 0–90, higher scores better), Hypoglycaemia Fear Survey II (range 0–72, higher scores worse) and Diabetes Treatment Satisfaction Questionnaire (range 0–36, higher scores better) were completed by 32 participants. Semi‐structured interviews were conducted after study completion in a subset of six participants. Outcomes were compared using a repeated‐measures anova model or paired t‐test when appropriate.

Results

The total artificial pancreas acceptance questionnaire score at the end of the artificial pancreas period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude towards the artificial pancreas. No significant differences were found among the scores at baseline, end of sensor‐augmented pump therapy period or end of the artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5), 23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P = 0.43]. Themes frequently mentioned in the interviews were ‘positive effects at work’, ‘improved blood glucose’, ‘fewer worries about blood glucose’, but also ‘frequent alarms’, ‘technological issues’ and ‘demand for an all‐in‐one device’.

Conclusions

The psychological outcomes of artificial pancreas and sensor‐augmented pump therapy were similar. Current artificial pancreas technology is promising but user concerns should be taken into account to ensure utility of these systems.
High and low vitamin D level is associated with cardiovascular autonomic neuropathy in people with Type 1 and Type 2 diabetes
Authors: Hansen C. S. , Fleischer J. , Vistisen D. , Ridderstråle M. , Jensen J. S. , Jørgensen M. E.
Published: October 2016

Aim

To investigate the possible association between vitamin D deficiency and cardiovascular autonomic neuropathy in people with diabetes.

Methods

A total of 113 people with Type 1 or Type 2 diabetes [mean (interquartile range) diabetes duration 22.0 (12–31) years, mean (sd) age 56.2 (13.0) years, 58% men] underwent vitamin D (D2 and D3) assessment, and were screened for cardiovascular autonomic neuropathy using three cardiovascular reflex tests [heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva manoeuvre] and assessment of 5‐min resting heart rate and heart rate variability indices.

Results

We found an inverse U‐shaped association between serum vitamin D level and E/I ratio, 30/15 ratio and three heart rate variability indices (P < 0.05). Vitamin D level was non‐linearly associated with cardiovascular autonomic neuropathy diagnosis (P < 0.05 adjusted for age and sex). Linear regression models showed that an increase in vitamin D level from 25 to 50 nmol/l was associated with an increase of 3.9% (95% CI 0.1;7.9) in E/I ratio and 4.8% (95% CI 4.7;9.3) in 30/15 ratio. Conversely, an increase from 125 to 150 nmol/l in vitamin D level was associated with a decrease of 2.6% (95% CI −5.8;0.1) and 4.1% (95% CI −5.8;−0.5) in the respective outcome measures.

Conclusions

High and low vitamin D levels were associated with cardiovascular autonomic neuropathy in people with diabetes. Future studies should explore this association and the efficacy of treating dysvitaminosis D to prevent cardiovascular autonomic neuropathy.
Echocardiographic assessment of right ventricular contractile reserve in healthy subjects
Authors: D'Alto Michele , Pavelescu Adriana , Argiento Paola , Romeo Emanuele , Correra Anna , Di Marco Giovanni Maria , D'Andrea Antonello , Sarubbi Berardo , Russo Maria Giovanna , Naeije Robert
Published: October 2016

Background

Exercise‐induced increase in pulmonary artery systolic pressure (PASP) as a possible measure of right ventricular (RV) contractile reserve has been shown to predict survival in severe pulmonary hypertension. However, RV contractile reserve can also be measured by changes in stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), or tricuspid annular systolic velocity (S'). The limits of normal values and the functional significance of these changes in healthy subjects are not well known.

Methods

In this prospective study, 90 healthy subjects (45 male, mean age 39 ± 13 years) underwent exercise stress echocardiography with measurement of TAPSE, S', TAPSE/PASP, SV, and PASP at rest and peak exercise. Maximum and minimum normal values were reported for all indices.

Results

Normal values of exercise‐induced changes (Δ) were 4 to 10 mm for TAPSE, 6 to 14 cm/s for S', 12 to 57 mm Hg for PASP, 0 to 96 mL for SV, and −1.2 to 0 mm/mm Hg for TAPSE/PASP. At peak exercise, women showed lower ΔTAPSE/PASP, ΔPASP, ΔS', and ΔSV, but higher TAPSE/PASP than men. Aging was associated with decreased ΔTAPSE/PASP, ΔTAPSE, ΔS', ΔPASP, and ΔSV. In addition, ΔS', ΔTAPSE/PASP, ΔPASP, and ΔSV, but not ΔTAPSE, were directly correlated with maximum workload.

Conclusions

Our results provide age‐ and sex‐related limits of normal for RV contractile reserve as assessed by exercise stress echocardiography and demonstrate that RV systolic function indices (PASP, TAPSE, S', and TAPSE/PASP) correlate with maximum exercise capacity.
PITFALLS IN TESTING FOR COINTEGRATION BETWEEN INEQUALITY AND THE REAL INCOME
Authors: Gueye Ghislain N. , Kim Hyeongwoo , Sorek Gilad
Published: October 2016

Frank (2009) constructed a comprehensive panel of state‐level income inequality measures using individual tax filing data from the Internal Revenue Service. Employing an array of cointegration exercises for the data, he reported a positive long‐run relationship between income inequality and the real income per capita in the United States. This article questions the validity of his findings. First, we suggest a misspecification problem in his approach regarding the order of integration in the inequality index, which shows evidence of nonstationarity only for the post‐1980 data. Second, we demonstrate that his findings are not reliable because the panel cointegration test he used requires cross‐section independence, which is inappropriate for the U.S. state‐level data. Employing panel tests that allow cross‐section dependence, we find no evidence of cointegration between inequality and the real income. (JEL D31, O40)
Iatrogenic fracture of the premaxilla during standing exodontia
Authors: Grant M. J. , Barnett T. P.
Published: October 2016

This case report describes a 17‐year‐old horse that presented with a history of oral dysphagia secondary to buccal slab fractures and apical infection in two cheek teeth. During standing surgery to remove the diseased cheek teeth, the horse sustained a bilateral comminuted fracture of the premaxilla. An audible crack was followed by bilateral epistaxis. Subsequent radiography revealed minimal displacement at the fracture sites and the horse responded well to conservative management without the need for additional fixation techniques. One year later, the fracture appeared completely healed on repeat radiography. This is an uncommon complication of standing dental procedures necessitating the use of a speculum but is noteworthy and may be important to consider and inform owners in such aged cases.
Managerialism Redux?
Authors: Pollitt Christopher
Published: October 2016

This paper argues that managerialism is still very much with us. NPM (one prominent manifestation of managerialism) is not dead. Alongside NPM, other species of managerialism have evolved. Across Europe patterns of management reform have been complex, with layers of traditional bureaucracy, NPM, other forms of managerialism and post‐NPM forms being sedimented on top of, or woven alongside, each other in a variety of national formations. The advent of austerity has led many governments to implement traditional, pre‐managerialist across‐the‐board cuts and freezes. Sometimes (as in the UK) these have been mixed with renewed NPM initiatives, and/or with post‐NPM ideas, such as partnership and networking. Overall, however, managerialism seems unlikely to offer a major part of any solution to problems of fiscal balance ‐ the sums that can be saved through greater efficiencies are substantial, but not large enough.
Intracellular amorphous carbonates uncover a new biomineralization process in eukaryotes
Authors: Martignier A. , Pacton M. , Filella M. , Jaquet J.‐M. , Barja F. , Pollok K. , Langenhorst F. , Lavigne S. , Guagliardo P. , Kilburn M. R. , Thomas C. , Martini R. , Ariztegui D.
Published: October 2016

Until now, descriptions of intracellular biomineralization of amorphous inclusions involving alkaline‐earth metal (AEM) carbonates other than calcium have been confined exclusively to cyanobacteria (Couradeau et al., 2012). Here, we report the first evidence of the presence of intracellular amorphous granules of AEM carbonates (calcium, strontium, and barium) in unicellular eukaryotes. These inclusions, which we have named micropearls, show concentric and oscillatory zoning on a nanometric scale. They are widespread in certain eukaryote phytoplankters of Lake Geneva (Switzerland) and represent a previously unknown type of non‐skeletal biomineralization, revealing an unexpected pathway in the geochemical cycle of AEMs. We have identified Tetraselmis cf. cordiformis (Chlorophyta, Prasinophyceae) as being responsible for the formation of one micropearl type containing strontium ([Ca,Sr]CO3), which we also found in a cultured strain of Tetraselmis cordiformis. A different flagellated eukaryotic cell forms barium‐rich micropearls [(Ca,Ba)CO3]. The strontium and barium concentrations of both micropearl types are extremely high compared with the undersaturated water of Lake Geneva (the Ba/Ca ratio of the micropearls is up to 800,000 times higher than in the water). This can only be explained by a high biological pre‐concentration of these elements. The particular characteristics of the micropearls, along with the presence of organic sulfur‐containing compounds—associated with and surrounding the micropearls—strongly suggest the existence of a yet‐unreported intracellular biomineralization pathway in eukaryotic micro‐organisms.
Carbon accrual rates, vegetation and nutrient dynamics in a regularly burned coppice woodland in Germany
Authors: Borchard Nils , Adolphs Timo , Beulshausen Friederike , Ladd Brenton , Gießelmann Urs C. , Hegenberg Dominik , Möseler Bodo M. , Amelung Wulf
Published: October 2016

Historically, large areas of forest in Europe were managed as coppice woodland to produce wood‐based fuel for the smelting industry. We hypothesized that this practice produced a legacy effect on current forest ecosystem properties. Specifically, we hypothesized that the historical form of coppicing may have produced a legacy of elevated stocks of soil organic carbon (SOC), nutrients and black carbon (BC) in soil as fire was routinely used in coppiced woodland to clear land. We further hypothesized that these changes in soil properties would result in increased biodiversity. To test these hypotheses, we sampled the surface soil (0–5, 5–10 and 10–20 cm) from a chronosequence of forest sites found in the Siegerland (Germany) that had been coppiced and burned 1, 2, 3.5, 6, 8, 11 and 17 years before present. Mature beech and spruce forests (i.e., >60 years) were also sampled as reference sites: to provide a hint of what might occur in the absence of human intervention. We measured stocks of SOC, BC, NO3‐N, P, K, Mg, as well as cation exchange and water‐holding capacity, and we mapped plant composition to calculate species richness and evenness. The results showed that coppicing in combination with burning soil and litter improved soil nutrient availability, enhanced biodiversity and increased SOC stocks. The SOC stocks and biodiversity were increased by a factor of three relative to those in the mature beech and spruce forests. This study shows that traditional coppicing practice may facilitate net C accrual rates of 20 t ha−1 yr−1 and maintain high biodiversity, indicating that aspects of traditional practice could be applied in current forest management to foster biodiversity and to mitigate climate change.
TAK1 maintains the survival of immunoglobulin λ‐chain‐positive B cells
Authors: Shinohara Hisaaki , Nagashima Takeshi , Cascalho Marilia I. , Kurosaki Tomohiro
Published: October 2016

TAK1 (MAP3K7) mediation of the IκB kinase (IKK) complex−nuclear factor‐κB (NF‐κB) pathway is crucial for the activation of immune response and to perpetuate inflammation. Although progress has been made to understand TAK1 function in the B‐cell receptor (BCR) signaling, the physiological roles of TAK1 in B‐cell development, particularly in the bone marrow (BM), remain elusive. Previous studies suggested that the IKK complex is required for the development of immunoglobulin light chain λ‐positive B cells, but not for receptor editing. In contrast, NF‐κB activity is suggested to be involved in the regulation of receptor editing. Thus, NF‐κB signaling in early B‐cell development is yet to be fully characterized. Therefore, we addressed the role of TAK1 in early B‐cell development. TAK1‐deficient mice showed significant reduction of BM Igλ‐positive B‐cell numbers without any alteration in the BCR editing. Furthermore, the expression of survival factor Bcl‐2 was reduced in TAK1‐deficient BM B cells as assessed by microarray and quantitative PCR analyses. Ex vivo over‐expression of exogenous Bcl‐2 enhanced the survival of TAK1‐deficient Igλ‐positive B cells. TAK1–IKK–NF‐κB signaling contributes to the survival of λ‐chain‐positive B cells through NF‐κB‐dependent anti‐apoptotic Bcl‐2 expression.
Groundwater Exploration in India Using Hydrogeological & Resistivity Method in Past 60 Years
Authors: Limaye Shrikant Daji
Published: October 2016

Article Impact Statement: Survival of private sector by developing and using low‐cost resistivity meters. Limitations experienced in hard‐rock terrain
Do Mother and Father Auditors Have Equal Prospects for Career Advancement?
Authors: Kristensen Rikke Holmslykke , Kent Pamela , Warming‐Rasmussen Bent , Windsor Carolyn
Published: October 2016

This research investigates whether parental role and gender are associated with career advancement for professional female and male auditors employed by international audit firms in Denmark. Management at four levels, from partner to lower level non‐management employee, are examined to determine whether a relationship holds between being a parent and gender. We find that more parents achieve advancement to higher levels of employment than non‐parents. However, mothers are significantly disadvantaged relative to fathers in achieving senior levels of employment. There is no significant difference in the likelihood of career advancement between female and male auditors that are not parents implied by a lack of significant results for the gender variable in the regression analyses. Years of experience also significantly explains career advancement in the organization while age is significantly correlated with experience of the auditor.
The kerion: an angry tinea capitis
Authors: John Ann M. , Schwartz Robert A. , Janniger Camila K.
Published: October 2016

Tinea capitis has a high incidence with a global changing pathogen distribution, making this condition a public health concern around the world. As the infection is initially asymptomatic, it is easily spread. Moreover, it is present in many fomites, including hairbrushes, pillows, and bedding. Prompt recognition and treatment is necessary for kerion, an inflammatory subtype characterized by tender boggy plaques with purulent drainage. Kerion is usually associated with infection by zoophilic dermatophytes, although other sources have been described. Treatment for this severe form of dermatophytic infection can be challenging. In addition to the use of topical treatments, oral administration of griseofulvin, terbinafine, itraconazole, or fluconazole is often required. Griseofulvin, the first‐line treatment, may not completely eradicate pathogen colonization of the host and may contribute to reinfection and prevalence of infective but asymptomatic carriers. This review highlights new agents that are being evaluated for the treatment of kerion and typical tinea capitis, enhanced diagnostic criteria, and a grading system for kerion evaluation.
Effects of psychosocial interventions on behavioural problems in youth: A close look at Cochrane and Campbell reviews
Authors: Karlsson Patrik , Bergmark Anders , Lundström Tommy
Published: October 2016

Research indicates that a number of psychosocial interventions are effective for reducing behavioural problems in youth. These interventions are now often included on best practice lists aiming to facilitate informed treatment choices among practitioners. However, analyses in neighbouring research areas have highlighted serious shortcomings in how primary studies are analysed and how studies are synthesised in research reviews. This study took a closer look at the evidence of efficacy for psychosocial interventions that aim to reduce behavioural problems in youth, as shown in systematic research reviews by the Cochrane and the Campbell Collaborations (n = 8). The findings suggest a bias towards overemphasising the efficacy of the interventions in several reviews, an over‐confidence in the validity of the findings in some reviews and, overall, a somewhat uncertain evidence base for the efficacy of the interventions. Systematic reviews are crucial for summarising research but more attention to methodological issues may be needed in this area.
Pedicled medial sural perforator flap for the reconstruction of knee defects
Authors: Chiang I‐Han , Wu Chia‐Chun , Chen Shyi‐Gen , Wang Chih‐Hsin
Published: October 2016

Soft tissue defects exposing the patellar tendon or bone are common in patients who have experienced trauma or implant infection. The purpose of this article is to present our experience of six patients who underwent reconstruction of soft tissue defects of the knee using a pedicled medial sural perforator flap. Between November 2013 and November 2015, six patients who presented with a soft tissue defect overlying the knee were admitted to our hospital. After adequate debridement or wide excision of the tumour, these patients underwent pedicled medial sural perforator flap placement to resurface the complex soft tissue defects and to provide a gliding surface for the exposed patellar tendon. The patients' age, comorbidity, aetiology, defect size and location, flap size, perforator numbers and lengths, outcome and follow‐up period were reviewed. The six medial sural perforator flaps survived completely, and the wounds healed satisfactorily over a mean follow‐up of 21·5 months (range, 6–51 months). Donor sites were closed primarily or covered with a split‐thickness skin graft. The medial sural perforator flap is a reliable flap for coverage of defects overlying the knee. The thin and pliable flap, long pedicle length and less donor site mobility benefit patients. Thus, the medial sural perforator flap may be a valuable alternative for defect reconstructions overlying the knee, which produces satisfactory results both functionally and cosmetically.
Distinct roles of immunoreceptor tyrosine‐based motifs in immunosuppressive indoleamine 2,3‐dioxygenase 1
Authors: Albini Elisa , Rosini Verdiana , Gargaro Marco , Mondanelli Giada , Belladonna Maria L. , Pallotta Maria Teresa , Volpi Claudia , Fallarino Francesca , Macchiarulo Antonio , Antognelli Cinzia , Bianchi Roberta , Vacca Carmine , Puccetti Paolo , Grohmann Ursula , Orabona Ciriana
Published: October 2016

The enzyme indoleamine 2,3‐dioxygenase 1 (IDO1) catalyses the initial, rate‐limiting step in tryptophan (Trp) degradation, resulting in tryptophan starvation and the production of immunoregulatory kynurenines. IDO1's catalytic function has long been considered as the one mechanism responsible for IDO1‐dependent immune suppression by dendritic cells (DCs), which are master regulators of the balance between immunity and tolerance. However, IDO1 also harbours immunoreceptor tyrosine‐based inhibitory motifs, (ITIM1 and ITIM2), that, once phosphorylated, bind protein tyrosine phosphatases, (SHP‐1 and SHP‐2), and thus trigger an immunoregulatory signalling in DCs. This mechanism leads to sustained IDO1 expression, in a feedforward loop, which is particularly important in restraining autoimmunity and chronic inflammation. Yet, under specific conditions requiring that early and protective inflammation be unrelieved, tyrosine‐phosphorylated ITIMs will instead bind the suppressor of cytokine signalling 3 (SOCS3), which drives IDO1 proteasomal degradation and shortens the enzyme half‐life. To dissect any differential roles of the two IDO1's ITIMs, we generated protein mutants by replacing one or both ITIM‐associated tyrosines with phospho‐mimicking glutamic acid residues. Although all mutants lost their enzymic activity, the ITIM1 – but not ITIM2 mutant – did bind SHPs and conferred immunosuppressive effects on DCs, making cells capable of restraining an antigen‐specific response in vivo. Conversely, the ITIM2 mutant would preferentially bind SOCS3, and IDO1's degradation was accelerated. Thus, it is the selective phosphorylation of either ITIM that controls the duration of IDO1 expression and function, in that it dictates whether enhanced tolerogenic signalling or shutdown of IDO1‐dependent events will occur in a local microenvironment.
MicroRNA let‐7g possesses a therapeutic potential for peripheral artery disease
Authors: Hsu Po‐Yuan , Hsi Edward , Wang Tzu‐Ming , Lin Ruey‐Tay , Liao Yi‐Chu , Juo Suh‐Hang H.
Published: October 2016

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and conveys a significant health burden globally. Critical limb ischaemia encompasses the most severe consequence of PAD. Our previous studies indicate that microRNA let‐7g prevents atherosclerosis and improves endothelial functions. This study aimed to investigate whether and how let‐7g therapy may improve blood flow to ischaemic limbs. The present study shows that let‐7g has multiple pro‐angiogenic effects on mouse ischaemic limb model and could be a potential therapeutic agent for PAD. Mice receiving intramuscular injection of let‐7g had more neovascularization, better local perfusion and increased recruitment of endothelial progenitor cells after hindlimb ischaemia. The therapeutic effects of let‐7g's on angiogenesis are mediated by multiple regulatory machinery. First, let‐7g increased expression of vascular endothelial growth factor‐A (VEGF‐A) and VEGF receptor‐2 (VEGFR‐2) through targeting their upstream regulators HIF‐3α and TP53. In addition, let‐7g affected the splicing factor SC35 which subsequently enhanced the alternative splicing of VEGF‐A from the anti‐angiogenic isoform VEGF‐A165b towards the pro‐angiogenic isoform VEGF‐A164a. The pleiotropic effects of let‐7g on angiogenesis imply that let‐7g may possess a therapeutic potential in ischaemic diseases.
Ghrelin is a possible new predictor associated with executive function in patients with type 2 diabetes mellitus
Authors: Chen Siting , Zuo Xuyang , Li Yuan , Jiang Tian , Zhang Nan , Dai Fang , Chen Qiaoer , Zhang Qiu
Published: October 2016

Aims/Introduction

The aim of the present research was to study the ghrelin level, executive function and their possible association in patients with type 2 diabetes mellitus.

Materials and Methods

A total of 370 people were recruited between March 2015 and March 2016 in this study. Among them, 212 participants were patients with type 2 diabetes mellitus and 158 participants were included as the control group. Their blood sample was analyzed for the level of ghrelin and other clinical indexes. Cognitive function was measured by the Montreal Cognitive Assessment, and executive function was evaluated by the Wisconsin Card Sorting Test.

Results

In the type 2 diabetes mellitus group, age, years of education, duration of diabetes, fasting blood glucose, glycated hemoglobin, hypertension and waist‐to‐hip ratio were correlated with total Montreal Cognitive Assessment scores. No association was found between ghrelin level and total Montreal Cognitive Assessment score in patients with type 2 diabetes mellitus. However, ghrelin was found to be a significant predictor for executive function impairment measured by the Wisconsin Card Sorting Test in patients with type 2 diabetes mellitus.

Conclusions

The level of serum ghrelin might be a biomarker of executive function and become a strong predictor of executive function impairment in patients with type 2 diabetes mellitus. Ghrelin might have a potential protective effect against cognitive function impairment in type 2 diabetes patients.
Treatment outcomes with ixekizumab in patients with moderate‐to‐severe psoriasis who have or have not received prior biological therapies: an integrated analysis of two Phase III randomized studies
Authors: Gottlieb A.B. , Lacour J.‐P. , Korman N. , Wilhelm S. , Dutronc Y. , Schacht A. , Erickson J. , Zhang L. , Mallbris L. , Gerdes S.
Published: October 2016

Background

Biologics are effective for the treatment of psoriasis. However, treatment outcomes may differ among biologic‐naive patients and those switched from previous biological therapies.

Objectives

The study's objective was to investigate efficacy and safety of ixekizumab, a high‐affinity anti‐interleukin‐17A antibody, in patients with psoriasis with and without previous exposure to biologics.

Methods

Data were integrated from the 12‐week induction phase of two etanercept‐controlled Phase III trials. Patients received 80 mg ixekizumab every 2 weeks (IXE Q2W; N = 736) or every 4 weeks (IXE Q4W; N = 733) following a 160‐mg starting dose, or placebo (N = 361). Etanercept (50 mg twice weekly; N = 740) was administered as active control. Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 response rates at week 12 were evaluated in patients with or without previous exposure to biologics. Treatment effects were analysed with the Cochran–Mantel–Haenszel test stratified by study; missing values were imputed as non‐response.

Results

Overall, 497 (19.3%) patients had prior exposure to biologics and 2073 (80.7%) were naive to biologic therapy. PASI 75 was achieved by 91.5% of biologic‐experienced patients and 87.7% of biologic‐naive patients for IXE Q2W, 76.2% and 82.2% for IXE Q4W, respectively, and 34.6% and 50.7%, respectively, for etanercept. Higher response rates favouring each ixekizumab dose over etanercept within subgroups were also seen regarding PASI 90 and PASI 100.

Conclusions

Contrary to etanercept, the efficacy of ixekizumab was similarly high in patients with and without previous exposure to biologics when administered 80 mg every 2 weeks.
TheARTof mating: alternative reproductive tactics and mating success in a nest‐guarding fish
Authors: Mascolino S. , Benvenuto C. , Gubili C. , Sacchi C. , Boufana B. , Mariani S.
Published: October 2016

Behavioural observations in the field of male Mediterranean damselfishChromis chromiswere combined with molecular analyses, using bi‐parentally and maternally inherited markers, to investigate reproductive success patterns of alternative reproductive tactics (ARTs) in terms of number of eggs sired and number of females contributing to each nest. Cuckoldry was observed in every nest sampled, with at least two and up to seven sneaker males per nest. The nesting male, however, always significantly fertilized the greater number of eggs (on average 49%) in each clutch, whereas each sneaker fertilized around 7% of the clutch. The average number of females whose eggs were fertilized by nesting males was 6·76 (range 2–13), while each sneaker on average fertilized the eggs of 1·74 (range 1–8) females. Using this sibship reconstruction, some of the factors involved in the regulation of the dynamic equilibrium of reproductive success were investigated between the twoARTsshown byC. chromismales. Results show that the sneakers' reproductive success was positively linked to egg clutch size; the density of individuals in the nesting area negatively affected the size of egg clutches; the rate of defence behaviours performed by nesting males negatively influenced the number of females contributing to each nest.
Toluene inhalation in adolescent rats reduces flexible behaviour in adulthood and alters glutamatergic and GABAergic signalling
Authors: Furlong Teri M. , Duncan Jhodie R. , Corbit Laura H. , Rae Caroline D. , Rowlands Benjamin D. , Maher Anthony D. , Nasrallah Fatima A. , Milligan Carol J. , Petrou Steven , Lawrence Andrew J. , Balleine Bernard W.
Published: October 2016

Toluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long‐term impact remains limited. Here, we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABAergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABAergic profile. Similarly, in vitro electrophysiology in Xenopus oocytes found that acute toluene exposure reduced NMDA receptor signalling. Finally, in an adolescent rodent model of chronic intermittent exposure to toluene (10 000 ppm), we found that, while toluene exposure did not affect initial learning, it induced a deficit in updating that learning when response‐outcome relationships were reversed or degraded in an instrumental conditioning paradigm. There were also group differences when more effort was required to obtain the reward; toluene‐exposed animals were less sensitive to progressive ratio schedules and to delayed discounting. These behavioural deficits were accompanied by changes in subunit expression of both NMDA and GABA receptors in adulthood, up to 10 weeks after the final exposure to toluene in the hippocampus, prefrontal cortex and ventromedial striatum; regions with recognized roles in behavioural flexibility and decision‐making. Collectively, our data suggest that exposure to toluene is sufficient to induce adaptive changes in glutamatergic and GABAergic systems and in adaptive behaviour that may underlie the deficits observed following adolescent inhalant abuse, including susceptibility to further drug‐use.

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Brefeldin A‐inhibited guanine nucleotide exchange protein 3 is localized in lysosomes and regulates GABA signaling in hippocampal neurons
Authors: Liu Tao , Li Hongyu , Hong Wanjin , Han Weiping
Published: October 2016

ADP‐ribosylation factor (ARF) family of guanine‐nucleotide‐binding (G) proteins regulates organelle biogenesis, structure and trafficking. The functions of ARF proteins are tightly controlled by guanine nucleotide exchange factors (GEFs) containing a conserved SEC7 domain. Based on sequence similarity to brefeldin A‐inhibited guanine nucleotide exchange protein (BIG)/GBF of the Arf‐GEF family, we recently identified BIG3 as a novel ARF GEF protein with a non‐functional catalytic motif in the SEC7 domain. BIG3 is mainly expressed in pancreatic islets and brain. In the islets, depletion of BIG3 increases insulin and glucagon secretion because of enhanced biogenesis of insulin and glucagon granules in the absence of BIG3. Here, we investigate BIG3 functions in the brain, in particular its regulation of neurotransmitter release in hippocampal neurons from wild‐type and BIG3 knockout mice. In hippocampal neurons, BIG3 is mainly localized in lysosomes, and its depletion selectively impairs inhibitory synaptic transmission. Our finding provides novel insights for a cell‐specific function of BIG3 in regulating neurotransmission.

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Children referred for specialty care: Parental perspectives and preferences on referral, follow‐up and primary care
Authors: Freed Gary L , Turbitt Erin , Kunin Marina , Gafforini Sarah , Sanci Lena , Spike Neil
Published: October 2016

Aim

Over the last decade, there has been a dramatic increase in the number of referrals for paediatric subspecialty care and in overall appointments (new and review) to these doctors. We sought to determine the perspective of parents regarding their role in the initiation of referrals, their preferences for follow‐up and the role of general practitioners (GPs) in care co‐ordination.

Methods

Self‐completed survey in outpatient paediatric clinics (general paediatrics and four subspecialties) at two children's hospitals in Victoria. Recruitment targets were 100 parents in each of the general paediatrics clinics and 50 parents in each subspecialty clinic, equally divided between new and review visits (total n = 600).

Results

A total of 606 parents provided responses, with a decline rate of 9%. Many (52%) new patients were referred by a GP with the remainder from a variety of other sources. With specific regard to providing general care to their child, only 45% were completely confident in a GP. Most (76%) agreed with the statement that a GP would give their child a referral to see a paediatrician whenever they ask. Approximately, a third of parents reported that a GP rarely or never co‐ordinates the care of their child with other doctors.

Conclusions

Parents play an important role in both the initiation of paediatric specialty referrals and the patterns of follow‐up care provided. Parent perspectives, preferences and motivations on both the referral process and the patterns for ongoing care are essential to develop policies that provide the best and most efficient care for children.
Analysis of the complete plastomes of three species of Membranoptera (Ceramiales, Rhodophyta) from Pacific North America
Authors: Hughey Jeffery R. , Hommersand Max H. , Gabrielson Paul W. , Miller Kathy Ann , Fuller Timothy
Published: October 2016

Next generation sequence data were generated and used to assemble the complete plastomes of the holotype of Membranoptera weeksiae, the neotype (designated here) of M. tenuis, and a specimen examined by Kylin in making the new combination M. platyphylla. The three plastomes were similar in gene content and length and showed high gene synteny to Calliarthron, Grateloupia, Sporolithon, and Vertebrata. Sequence variation in the plastome coding regions were 0.89% between M. weeksiae and M. tenuis, 5.14% between M. weeksiae and M. platyphylla, and 5.18% between M. tenuis and M. platyphylla. We were unable to decipher the complete mitogenomes of the three species due to low coverage and structural problems; however, we assembled and analyzed, the cytochrome oxidase I, II, and III loci and found that M. weeksiae and M. tenuis differed in sequence by 1.3%, M. weeksiae and M. platyphylla by 8.4%, and M. tenuis and M. platyphylla by 8.1%. Evaluation of standard marker genes indicated that sequences from the rbcL, RuBisCO spacer, and CO1 genes closely approximated the pair‐wise genetic distances observed between the plastomes of the three species of Membranoptera. A phylogenetic tree based on rbcL sequences showed that M. tenuis and M. weeksiae were sister taxa. Short rbcL sequences were obtained from type specimens of M. dimorpha, M. multiramosa, and M. edentata and confirmed their conspecificity with M. platyphylla. The data support the recognition of three species of Membranoptera occurring south of Alaska: M. platyphylla, M. tenuis, and M. weeksiae.
High cholesterol dietary intake during pregnancy is associated with large for gestational age in a sample of low‐income women of Rio de Janeiro, Brazil
Authors: de Castro Maria Beatriz Trindade , Farias Dayana Rodrigues , Lepsch Jaqueline , Mendes Roberta Hack , Ferreira Aline Alves , Kac Gilberto
Published: October 2016

The association between the quality of maternal dietary fat intake during pregnancy and the infant's birthweight (BW) remains controversial. Our goal was to investigate the association between maternal dietary fat intake during pregnancy and the rate of large for gestational age (LGA) newborns. This study employed a cross‐sectional analysis of 297 pairs of mothers/children attending a public maternity at Rio de Janeiro, Brazil. BW for gestational age according to the Intergrowth 21st was defined as follows: adequate for gestational age (AGA ≤ 90th percentile) and LGA (>90th percentile). The statistical analysis was a Poisson regression with robust estimations of the standard errors. Maternal dietary fat intake variables comprised lipids (% total energy); saturated (mg/1000 kcal), monounsaturated (mg/1000 kcal) and polyunsaturated (mg/1000 kcal) fats; and cholesterol (mg/1000 kcal), all of which were obtained with a Food Frequency Questionnaire. The mean BW was 3338 g (SD = 446.9), and the rate of LGA newborns was 13.1%. The mean maternal total energy intake was 2880 kcal (SD = 1074), cholesterol was 154.3 mg/1000 kcal (SD = 68.1) and monounsaturated fat was 6.9 mg/1000 kcal (SD = 2). Mothers of LGA newborns reported higher cholesterol dietary intake (195.8 vs. 148 mg/1000 kcal; P < 0.001), pre‐pregnancy body mass index (25.1 vs. 23.5 kg/m2; P = 0.026) when compared with mothers of AGA newborns. Women with cholesterol intake within the fourth quartile were 2.48 (95% confidence interval: 1.31–4.66) times more likely to have an LGA infant compared with those in the 1–3 quartiles. Dietary intake of cholesterol during pregnancy influences LGA even after adjusting for other confounders.
The fungal cultivar of leaf‐cutter ants produces specific enzymes in response to different plant substrates
Authors: Khadempour Lily , Burnum‐Johnson Kristin E. , Baker Erin S. , Nicora Carrie D. , Webb‐Robertson Bobbie‐Jo M. , White Richard A. , Monroe Matthew E. , Huang Eric L. , Smith Richard D. , Currie Cameron R.
Published: October 2016

Herbivores use symbiotic microbes to help derive energy and nutrients from plant material. Leaf‐cutter ants are a paradigmatic example, cultivating their mutualistic fungus Leucoagaricus gongylophorus on plant biomass that workers forage from a diverse collection of plant species. Here, we investigate the metabolic flexibility of the ants’ fungal cultivar for utilizing different plant biomass. Using feeding experiments and a novel approach in metaproteomics, we examine the enzymatic response of L. gongylophorus to leaves, flowers, oats or a mixture of all three. Across all treatments, our analysis identified and quantified 1766 different fungal proteins, including 161 putative biomass‐degrading enzymes. We found significant differences in the protein profiles in the fungus gardens of subcolonies fed different plant substrates. When provided with leaves or flowers, which contain the majority of their energy as recalcitrant plant polymers, the fungus gardens produced more proteins predicted to break down cellulose: endoglucanase, exoglucanase and β‐glucosidase. Further, the complete metaproteomes for the leaves and flowers treatments were very similar, while the mixed substrate treatment closely resembled the treatment with oats alone. This indicates that when provided a mixture of plant substrates, fungus gardens preferentially break down the simpler, more digestible substrates. This flexible, substrate‐specific enzymatic response of the fungal cultivar allows leaf‐cutter ants to derive energy from a wide range of substrates, which likely contributes to their ability to be dominant generalist herbivores.
The Paracoccus denitrificansNarK‐like nitrate and nitrite transporters—probing nitrate uptake and nitrate/nitrite exchange mechanisms
Authors: Goddard Alan D. , Bali Shilpa , Mavridou Despoina A.I. , Luque‐Almagro Victor M. , Gates Andrew J. , Dolores Roldán M. , Newstead Simon , Richardson David J. , Ferguson Stuart J.
Published: October 2016

Nitrate and nitrite transport across biological membranes is often facilitated by protein transporters that are members of the major facilitator superfamily. Paracoccus denitrificans contains an unusual arrangement whereby two of these transporters, NarK1 and NarK2, are fused into a single protein, NarK, which delivers nitrate to the respiratory nitrate reductase and transfers the product, nitrite, to the periplasm. Our complementation studies, using a mutant lacking the nitrate/proton symporter NasA from the assimilatory nitrate reductase pathway, support that NarK1 functions as a nitrate/proton symporter while NarK2 is a nitrate/nitrite antiporter. Through the same experimental system, we find that Escherichia coli NarK and NarU can complement deletions in both narK and nasA in P. denitrificans, suggesting that, while these proteins are most likely nitrate/nitrite antiporters, they can also act in the net uptake of nitrate. Finally, we argue that primary sequence analysis and structural modelling do not readily explain why NasA, NarK1 and NarK2, as well as other transporters from this protein family, have such different functions, ranging from net nitrate uptake to nitrate/nitrite exchange.
The changing definition of China in middle school history textbooks
Authors: Lu Zhaojin
Published: October 2016

Inspired by the dichotomous understanding of nationhood contributed by Brubaker (1992), this paper explores how Chinese nationhood is constituted by particular symbols in middle school historiography since the 1950s. In response to the analysis on the high school textbooks done by Baranovitch (2000), this study finds that the narratives in the middle school history textbooks have a similar transition from equating China to Han to defining China as a multi‐ethnic nation. However, the analysis also demonstrates that the transition of the middle school history textbooks is not as complete and absolute as that of their high school counterparts. A textbook may follow different principles in nationhood configuration simultaneously. In the textbook narratives before the change, the jus sanguinis logic was dominant over the jus soli logic; in those in the textbooks after the change, Chinese nationhood was constituted by the jus soli principle and the jus sanguinis principle complementarily. This study questions the perception that a nation only consistently follows one philosophy in the symbolic consolidation of nationhood, and casts doubt on the understanding that jus sanguinis or jus soli logic is deeply rooted in the historical development of a nation and cannot change.