bluuebunny/crossref_metadata_2025 huggingface dataset:
El desafío y futuro de la simulación como estrategia de enseñanza en enfermería
Authors: Urra Medina Eugenia , Sandoval Barrientos Sandra , Irribarren Navarro Fabio
Published: March 2017

La simulación ha sido usada, desde hace décadas, en la enseñanza curricular de la enfermería, constituyéndose en una estrategia eficaz para la formación clínica. Una revisión de la literatura nos permitirá reflexionar al cuestionar su evolución, y cómo esta metodología puede ser incorporada en el currículo con modelos educativos integrados y evaluados para asegurar una enseñanza adecuada y efectiva. Hay que considerar los dilemas en su uso, y tener presente los límites de la realidad y su representación. Lo anterior tiene implicaciones en la naturaleza esencial de la enfermería: el cuidado de los seres humanos.
Grand Coalitions and Democratic Dysfunction: Two Warnings from Central Europe
Authors: Jacoby Wade
Published: March 2017

Are ‘grand coalitions’ – coalitions that include the two largest parties in a parliamentary system – good or bad for democracy? This article analyses that question in light of the recent rise of populist parties that large mainstream parties may try to exclude from government by forming grand coalitions with other large mainstream parties. I call this the ‘sterilization’ logic and note that mainstream parties’ ability to do this varies widely. Where parties have previously used grand coalitions primarily according to a ‘clientelistic’ logic – for example, Austria – mainstream parties may well be unable to rally the party system against insurgent populist challengers. Where mainstream parties have used grand coalitions exceptionally and for major institutional ‘renovations’ – for example, Germany – the grand coalition remains a viable option for responding to insurgent challenges, though this strategy is also quite risky. This article considers the implications for democracy by tracing recent developments in the context of the euro crisis and the European refugee situation. The major empirical referents are Austria and Germany – two countries with extensive experience and literature about grand coalitions – but the article draws out the implications of the analysis for other European parliamentary contexts.
Ship generated mini-tsunamis
Authors: Grue John
Published: March 2017

Very long waves are generated when a ship moves across an appreciable depth change $\unicode[STIX]{x0394}h$ comparable to the average and relatively shallow water depth $h$ at the location, with $\unicode[STIX]{x0394}h/h\simeq 1$. The phenomenon is new and the waves were recently observed in the Oslofjord in Norway. The 0.5–1 km long waves, extending across the 2–3 km wide fjord, are observed as run-ups and run-downs along the shore, with periods of 30–60 s, where a wave height up to 1.4 m has been measured. The waves travelling with the shallow water speed, found ahead of the ships moving at subcritical depth Froude number, behave like a mini-tsunami. A qualitative explanation of the linear generation mechanism is provided by an asymptotic analysis, valid for $\unicode[STIX]{x0394}h/h\ll 1$ and long waves, expressing the generation in terms of a pressure impulse at the depth change. Complementary fully dispersive calculations for $\unicode[STIX]{x0394}h/h\simeq 1$ document symmetries of the waves at positive or negative $\unicode[STIX]{x0394}h$. The wave height grows with the ship speed $U$ according to $U^{n}$ with $n$ in the range 3–4, for $\unicode[STIX]{x0394}h/h\simeq 1$, while the growth in $U$ is only very weak for $\unicode[STIX]{x0394}h/h\ll 1$ (the asymptotics). Calculations show good agreement with observations.
Exceptionally preserved conodont apparatuses with giant elements from the Middle Ordovician Winneshiek Konservat-Lagerstätte, Iowa, USA
Authors: Liu Huaibao P. , Bergström Stig M. , Witzke Brian J. , Briggs Derek E. G. , McKay Robert M. , Ferretti Annalisa
Published: March 2017

Considerable numbers of exceptionally preserved conodont apparatuses with hyaline elements are present in the middle-upper Darriwilian (Middle Ordovician, Whiterockian) Winneshiek Konservat-Lagerstätte in northeastern Iowa. These fossils, which are associated with a restricted biota including other conodonts, occur in fine-grained clastic sediments deposited in a meteorite impact crater. Among these conodont apparatuses, the common ones are identified asArcheognathus primusCullison, 1938 andIowagnathus grandisnew genus new species. The 6-element apparatus ofA.primuscomprises two pairs of archeognathiform (P) and one pair of coleodiform (S) elements. The 15-element apparatus ofI.grandisn. gen. n. sp. is somewhat reminiscent of the prioniodinid type and contains ramiform elements of alate (one element) and digyrate, bipennate, or tertiopedate types (7 pairs). Both conodont taxa are characterized by giant elements and the preservation of both crowns and basal bodies, the latter not previously reported in Ordovician conodont apparatuses. Comparison of the apparatus size in the Winneshiek specimens with that of the Scottish Carboniferous soft-part-preserved conodont animals suggests that the Iowa animals were significantly larger than the latter. The apparatus ofA.primusdiffers conspicuously from the apparatuses of the prioniodontidPromissumfrom the Upper Ordovician Soom Shale of South Africa although the apparatus architecture ofI.grandisn. gen. n. sp. shows some similarity to it. Based on the Winneshiek collections, a new family Iowagnathidae in Conodonta is proposed.
THOMAS ADÈS'STHE EXTERMINATING ANGEL
Authors: Venn Edward
Published: March 2017

Thomas Adès's third opera,The Exterminating Angel, is based closely upon Luis Buñuel's 1962 filmEl ángel exterminador, in which the hosts and guests at a high-society dinner party find themselves inexplicably unable to leave the dining room. Initial critical response to the opera too often focused on superficial similarities and discrepancies between the two works at the expense of attending to the specifically musical ways in which Adès presented the drama. This article explores the role that repetition plays in the opera, and in particular how repetitions serve both as a means of critiquing bourgeois sensibilities and as a representation of (loss of) will. I conclude by drawing on the work of Deleuze in order to situate the climax of the opera against the notion of the eternal return, highlighting how the music articulates the dramatic failure of the characters to escape.
Progress in Clinical Neurosciences A Systematic Review of the Use of Triptans in Acute Migraine
Authors: Gawel Marek J. , Worthington Irene , Maggisano Anne
Published: March 2017

Objective:

A systematic review of the literature was undertaken, to consolidate evidence concerning the efficacy and safety of triptans currently available in Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide guidelines for selection of a triptan.

Methods:

Data from published, randomized, placebo-controlled trials were pooled and a combined number needed to treat (NNT) and number needed to harm (NNH) was generated for each triptan. Direct comparative trials of triptans were also examined.

Results:

The lowest NNTfor headache response/pain-free at one/two hours is observed with subcutaneous sumatriptan. Among the oral formulations, the lowest NNT is observed with rizatriptan and the highest NENT with naratriptan. The lowest NNH is observed with subcutaneous sumatriptan.

Conclusions:

Triptans are relatively safe and effective medications for acute migraine attacks. However, differences among them are relatively small. Considerations in selecting a triptan include individual patient response/tolerance, characteristics of the attacks, relief of associated symptoms, consistency of response, headache recurrence, delivery systems and patient preference.
Intraoperative Fiber-Optic Endoscopy for Ventricular Catheter Insertion
Authors: Theodosopoulos Philip V. , Abosch Aviva , McDermott Michael W.
Published: March 2017

Objective:

Ventricular catheter placement is a common neurosurgical procedure often resulting in inaccurate intraventricular positioning. We conducted a comparison of the accuracy of endoscopic and conventional ventricular catheter placement in adults.

Methods:

A retrospective analysis of data was performed on 37 consecutive patients undergoing ventriculo-peritoneal shunt (VPS) insertion with endoscopy and 40 randomly selected, unmatched patients undergoing VPS insertion without endoscopy, for the treatment of hydrocephalus of varied etiology. A grading system for catheter tip position was developed consisting of five intraventricular zones, V1-V5, and three intraparenchymal zones, A, B, C. Zones V1 for the frontal approaches and V1 or V2 for the occipital approaches were the optimal catheter tip locations. Postoperative scans of each patient were used to grade the accuracy of ventricular catheter placement.

Results:

Seventy-six percent of all endoscopic ventricular catheters were in zone V1 and 100% were within zones V1-V3. No endoscopically inserted catheters were observed in zones V4, V5 or intraparenchymally. Thirty-eight percent of the conventionally placed catheters were in zone V1, 53% in zones V1-3 and 15% intraparenchymally. There was a statistically significant difference in the percentage of catheters in optimal location versus in any other location, favoring endoscopic guidance (p<0.001).

Conclusion:

We conclude that endoscopic ventricular catheter placement provides improved positioning accuracy than conventional techniques.
Spinal Angiolipoma
Authors: Fourney Daryl R. , Tong Karen A. , Macaulay Robert J.B. , Griebel Robert W.
Published: March 2017

Background:

Spinal epidural angiolipoma is a rare cause of spinal cord compression. We present a case and review the clinical presentation, radiological appearance, pathological aspects and treatment of this distinct clinico-pathological entity.

Methods:

A case of a 46-year-old woman with a five-month history of progressive myelopathy affecting her lower extremities is presented. CT and MRI revealed a large epidural fat-containing mass compressing the spinal cord dorsally at the T7-T8 level. A laminectomy was performed with gross total resection of the lesion.

Results:

The patient's neurologic symptoms improved postoperatively. A two-year follow-up period has revealed no signs of tumor recurrence and no neurological deficit.

Conclusion:

The diagnosis of spinal angiolipoma should be considered in the differential diagnosis of spinal cord compression. Magnetic resonance imaging is the investigation of choice. The surgical objective is complete excision but, for anterior lesions involving bone, an overly aggressive approach should be tempered by an awareness of the overall indolent natural history of so-called "infiltrating" spinal angiolipomas that are only partially excised.
Improved Outcomes in Stroke Thrombolysis with Pre-specified Imaging Criteria
Authors: Silver Brian , Demaerschalk Bart , Merino José G. , Wong Edward , Tamayo Arturo , Devasenapathy Ashok , O'Callaghan Christina , Kertesz Andrew , Young G. Bryan , Fox Allan J. , Spence J. David , Hachinski Vladimir
Published: March 2017

Background:

A 1995 National Institute of Neurological Disorders (NINDS) study found benefit for intravenous tissue plasminogen activator (tPA) in acute ischemic stroke (AIS). The symptomatic intracranial hemorrhage (SICH) rate in the NINDS study was 6.4%, which may be deterring some physicians from using this medication.

Methods:

Starting December 1, 1998, patients with AIS in London, Ontario were treated according to NINDS criteria with one major exception; those with approximately greater than one-third involvement of the idealized middle cerebral artery (MCA) territory on neuroimaging were excluded from treatment. The method used to estimate involvement of one-third MCA territory involvement bears the acronym ICE and had a median kappa value of 0.80 among five physicians. Outcomes were compared to the NINDS study.

Results:

Between December 1, 1998 and February 1, 2000, 30 patients were treated. Compared to the NINDS study, more London patients were treated after 90 minutes (p<0.00001) and tended to be older. No SICH was observed. Compared to the treated arm of the NINDS trial, fewer London patients were dead or severely disabled at three months (p=0.04). Compared to the placebo arm of the trial, more patients made a partial recovery at 24 hours (p=0.02), more had normal outcomes (p=0.03) and fewer were dead or severely disabled at three months (p=0.004).

Conclusions:

The results of the NINDS study were closely replicated and, in some instances, improved upon in this small series of Canadian patients, despite older age and later treatment. These findings suggest that imaging exclusion criteria may optimize the benefits of tPA.
Estimating gonorrhoea prevalence in young heterosexual men and women attending community-based sexual health services to inform decisions on gonorrhoea testing
Authors: TOWN K. , FUREGATO M. , FIELD N. , HUGHES G.
Published: March 2017

In England, dual tests detecting chlamydia and gonorrhoea are used in specialist and community-based sexual health services (SHSs). Test performance is poor when prevalence is low, therefore UK national guidelines recommend against opportunistic gonorrhoea screening unless there is a clear local public health need. While surveillance data on gonorrhoea prevalence is comprehensive in specialist SHSs, it is sparse in community SHSs. We aimed to estimate gonorrhoea prevalence in heterosexual men and women aged 15–24 attending community SHSs to inform testing care pathways. We used linear and quadratic regression to model the relationship between prevalence in community and specialist SHSs in local authorities (LAs) with available surveillance data. We applied best-fitting models to predict prevalence in community SHSs in remaining LAs. Data from community SHSs were available for 102/326 LAs. There was a weak positive association between gonorrhoea prevalence in community and specialist SHSs in corresponding LAs within (R2 = 0·13, P = 0·058) and outside (R2 = 0·07, P = 0·02) London. Applying best-fitting models, we estimated a median gonorrhoea prevalence of 0·5% (mean 0·6%; range 0·2%–2·7%) in heterosexuals attending community SHSs. Despite some unexplained variation, our analyses suggest gonorrhoea prevalence in young heterosexuals attending community SHSs is below 1% in most English LAs. Our findings re-inforce the current national guidelines that recommend care pathways for gonorrhoea testing in community SHSs include confirmatory testing to reduce the risk of misdiagnosis and inappropriate management.
Introduction: Austerity, Welfare and Social Citizenship
Authors: Edmiston Daniel , Patrick Ruth , Garthwaite Kayleigh
Published: March 2017

Since the global financial crisis in 2008, an ‘austerity consensus’ has emerged across many advanced capitalist economies (Farnsworth and Irving, 2012). Despite differing institutional settings, there has been a notable degree of convergence on fiscal consolidation (Farnsworth and Irving, 2012; Taylor-Gooby, 2012). Alongside this, political administrations have repeatedly claimed that welfare profligacy and dependency are key causes of public sector debt and economic stagnation. On this basis, political leaders have cultivated a policy mandate to re-configure working-age welfare and constrain public social expenditure in this domain. Taken together, these reforms represent a ‘new, more constrained and qualitatively different deal for citizens’ (Dwyer and Wright, 2014: 33). The central objective of this themed section is to explore the impact of these developments and their significance for the shifting character and operation of social citizenship in countries pursuing a similar strategy of ‘welfare austerity’ (MacLeavy, 2011: 360).
Duration of Soil Activity of Foramsulfuron Plus Thiencarbazone-methyl Applied to Weed Species Typical of Sugar Beet Cultivation
Authors: Wendt Moritz J. , Kenter Christine , Ladewig Erwin , Wegener Martin , Märländer Bernward
Published: March 2017

The duration of the soil activity of an acetolactate synthase-(ALS) inhibiting herbicide which is currently under approval for sugar beet cultivation was determined in a field trial series in Germany in 2013 and 2014. The herbicide containing foramsulfuron (FSN; 50 g L−1) and thiencarbazone-methyl (TCM; 30 g L−1) was applied in different dosages (25+15, 37.5+22.5 and 50+30 g FSN+TCM ha−1) to the bare soil. Five weed species (rapeseed, common lambsquarters, wild chamomile, blackgrass, barnyardgrass) were sown at 5, 10, 15 and 20d after application. The duration of the soil activity was assessed by determining percent weed control in the treated plots. The longest duration was observed after applying 50+30 g FSN+TCM ha−1, but the influence of environment was much stronger than the dosage effect. The mean duration of soil activity was 10 to 15 d in 2013 and longer than 20 d in 2014. Differences among weed species in their response to the herbicide treatments were small.
Oral health and oral health-related habits of Finnish prisoners
Authors: Vainionpää Raija , Peltokangas Arto , Leinonen Jukka , Pesonen Paula , Laitala Marja-Liisa , Anttonen Vuokko
Published: March 2017

Objectives/Aims:

This cross-sectional study aimed to examine oral health and oral health-related habits among prisoners at the Pelso Prison in Finland.

Materials and Methods:

Participants in this cross-sectional study comprises 100 inmates. A calibrated dentist recorded the decayed, filled and missed teeth as well as periodontal status (bleeding-on-probing, pocket probing and Community Periodontal Index) among the participants (n=100). Fifty inmates were also interviewed for marital status, education and oral health-related habits. The Ethical Committee of the Northern Ostrobothnia Hospital District and the Criminal Sanctions Agency approved the study protocol.

Results:

The participants were on average 35 years old and had 5 (s.d. 5.1) decayed teeth in need of restorative treatment, whereas DMFT was 17 (s.d. 8.9). Half of the study population had periodontal disease in need of professional treatment. Almost all reported brushing their teeth daily. Two-third ate sweets, one-third drank fizzy drinks and majority smoked every day. Almost two-third had used illicit drugs at some point of their lives. Almost all drunk alcohol once a week or more often. No statistically significant associations were discovered between dental treatment need and explanatory factors.

Discussion

Prisoners appear to be a homogenous group with poor oral health and harmful health behaviours.
Motor planning flexibly optimizes performance under uncertainty about task goals
Authors: Wong Aaron L. , Haith Adrian M.
Published: March 2017

In an environment full of potential goals, how does the brain determine which movement to execute? Existing theories posit that the motor system prepares for all potential goals by generating several motor plans in parallel. One major line of evidence for such theories is that presenting two competing goals often results in a movement intermediate between them. These intermediate movements are thought to reflect an unintentional averaging of the competing plans. However, normative theories suggest instead that intermediate movements might actually be deliberate, generated because they improve task performance over a random guessing strategy. To test this hypothesis, we vary the benefit of making an intermediate movement by changing movement speed. We find that participants generate intermediate movements only at (slower) speeds where they measurably improve performance. Our findings support the normative view that the motor system selects only a single, flexible motor plan, optimized for uncertain goals.
Pupil-linked arousal is driven by decision uncertainty and alters serial choice bias
Authors: Urai Anne E. , Braun Anke , Donner Tobias H.
Published: March 2017

While judging their sensory environments, decision-makers seem to use the uncertainty about their choices to guide adjustments of their subsequent behaviour. One possible source of these behavioural adjustments is arousal: decision uncertainty might drive the brain’s arousal systems, which control global brain state and might thereby shape subsequent decision-making. Here, we measure pupil diameter, a proxy for central arousal state, in human observers performing a perceptual choice task of varying difficulty. Pupil dilation, after choice but before external feedback, reflects three hallmark signatures of decision uncertainty derived from a computational model. This increase in pupil-linked arousal boosts observers’ tendency to alternate their choice on the subsequent trial. We conclude that decision uncertainty drives rapid changes in pupil-linked arousal state, which shape the serial correlation structure of ongoing choice behaviour.
Zyxin regulates endothelial von Willebrand factor secretion by reorganizing actin filaments around exocytic granules
Authors: Han Xiaofan , Li Pin , Yang Zhenghao , Huang Xiaoshuai , Wei Guoqin , Sun Yujie , Kang Xuya , Hu Xueting , Deng Qiuping , Chen Liangyi , He Aibin , Huo Yingqing , Li Dong , Betzig Eric , Luo Jincai
Published: March 2017

Endothelial exocytosis of Weibel–Palade body (WPB) is one of the first lines of defence against vascular injury. However, the mechanisms that control WPB exocytosis in the final stages (including the docking, priming and fusion of granules) are poorly understood. Here we show that the focal adhesion protein zyxin is crucial in this process. Zyxin downregulation inhibits the secretion of von Willebrand factor (VWF), the most abundant cargo in WPBs, from human primary endothelial cells (ECs) induced by cAMP agonists. Zyxin-deficient mice exhibit impaired epinephrine-stimulated VWF release, prolonged bleeding time and thrombosis, largely due to defective endothelial secretion of VWF. Using live-cell super-resolution microscopy, we visualize previously unappreciated reorganization of pre-existing actin filaments around WPBs before fusion, dependent on zyxin and an interaction with the actin crosslinker α-actinin. Our findings identify zyxin as a physiological regulator of endothelial exocytosis through reorganizing local actin network in the final stage of exocytosis.
Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction
Authors: Tang Juan , Shen Yujun , Chen Guilin , Wan Qiangyou , Wang Kai , Zhang Jian , Qin Jing , Liu Guizhu , Zuo Shengkai , Tao Bo , Yu Yu , Wang Junwen , Lazarus Michael , Yu Ying
Published: March 2017

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chigh) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6Clow Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signalling and subsequently inhibits Ly6Clow Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE2/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6Clow Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.
Dietary Flavonoids, CYP1A1 Genetic Variants, and the Risk of Colorectal Cancer in a Korean population
Authors: Cho Young Ae , Lee Jeonghee , Oh Jae Hwan , Chang Hee Jin , Sohn Dae Kyung , Shin Aesun , Kim Jeongseon
Published: March 2017

The role of dietary flavonoid intake in colorectal carcinogenesis might differ according to flavonoid subclasses and individual genetic variants related to carcinogen metabolism. Therefore, we examined whether greater dietary intake of flavonoid subclasses was associated with a lower risk of colorectal cancer and whether CYP1A1 genetic variants altered this association. A semi-quantitative food frequency questionnaire was used to assess the dietary intake of six flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, anthocyanidins, and isoflavones) in 923 patients with colorectal cancer and 1,846 controls; furthermore, CYP1A1 genetic variants (rs4646903 and rs1048943) were genotyped. Among the subclasses of flavonoids, higher intake of flavonols and flavan-3-ols showed a stronger association with a reduced risk of colorectal cancer after adjusting for potential confounding factors. Carriers of the CYP1A1 rs4646903 CC homozygous variant showed a reduced risk of rectal cancer compared with that in TT carriers. The inverse association between dietary flavonol intake and colorectal cancer risk was stronger among carriers of the CC homozygous variant than among T allele carriers (P for interaction = 0.02), particularly for rectal cancer (P for interaction = 0.005). In conclusion, the effect of dietary flavonoid intake on colorectal cancer risk differs according to flavonoid subclasses and CYP1A1 genetic variants.
Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)
Authors: Waugh Courtney A. , Hanger Jonathan , Loader Joanne , King Andrew , Hobbs Matthew , Johnson Rebecca , Timms Peter
Published: March 2017

The virulence of chlamydial infection in wild koalas is highly variable between individuals. Some koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppressive effect of KoRV in vitro. Originally thought to be a single endogenous strain, a new, potentially more virulent exogenous variant (KoRV-B) was recently reported. We hypothesized that KoRV-B might significantly alter chlamydial disease outcomes in koalas, presumably via immunosuppression. By studying sub-groups of Chlamydia and KoRV infected koalas in the wild, we found that neither total KoRV load (either viraemia or proviral copies per genome), nor chlamydial infection level or strain type, was significantly associated with chlamydial disease risk. However, PCR positivity with KoRV-B was significantly associated with chlamydial disease in koalas (p = 0.02961). This represents an example of a recently evolved virus variant that may be predisposing its host (the koala) to overt clinical disease when co-infected with an otherwise asymptomatic bacterial pathogen (Chlamydia).
A systematic review and meta-analysis of T2, T3 or T4, to evaluate the best denervation level for palmar hyperhidrosis
Authors: Zhang Wenxiong , Yu Dongliang , Wei Yiping , Xu Jianjun , Zhang Xiaoqiang
Published: March 2017

We systematically reviewed and compared the clinical outcomes of thoracoscopic sympathectomy (TS) at different denervation levels for palmar hyperhidrosis. We searched PubMed, Ovid MEDLINE, EMBASE, Web of Science, ScienceDirect, the Cochrane Library, Scopus and Google Scholar for relevant studies published during 1990–2016. Symptom resolution, patient satisfaction, compensatory sweating (CS), recurrence, dry hands and gustatory sweating were assessed. We selected 13 studies from 2228 for the final analysis. A comparison of T2 vs. T3 TS revealed that T3 TS reduced the risk of CS (95% confidence interval [CI]: 1.36–3.19, p = 0.0007) and moderate-to-severe CS (95% CI: 2.14–7.87, p < 0.0001). No significant differences were found in patient satisfaction, symptom resolution, and incidence of dry hands and gustatory sweating. A comparison of T3 vs. T4 TS revealed that T4 TS reduced the risk of CS (95% CI: 2.87–9.53, p < 0.00001), moderate-to-severe CS (95% CI: 2.54–5.83, p < 0.00001), dry hands (95% CI: 4.07–18.13, p < 0.00001) and gustatory sweating (95% CI: 1.53–7.32, p < 0.003), and improved patient satisfaction. No significant differences were found in symptom resolution and recurrence. T4 TS appears to be more useful than T3 or T2 TS for PH.
Temperature Effect on the Stability of the Polarized State Created by Local Electric Fields in Strontium Barium Niobate Single Crystals
Authors: Shur V. Ya. , Shikhova V. A. , Alikin D. O. , Lebedev V. A. , Ivleva L. I. , Dec J. , Lupascu D. C. , Shvartsman V. V.
Published: March 2017

The stability of ferroelectric domain patterns at the nanoscale has been a topic of much interest for many years. We investigated the relaxation of the polarized state created by application of a local electric field using a conductive tip of a scanning probe microscope for the model uniaxial relaxor system SrxBa1−xNb2O6 (SBN) in its pure and Ce-doped form. The temporal relaxation of the induced PFM contrast was measured at various temperatures. The average value of the induced contrast decreases during heating for all investigated crystals. Below the freezing temperature the induced state remains stable after an initial relaxation. Above the freezing temperature the induced state is unstable and gradually decays with time. The stability of the induced state is strongly affected by the measuring conditions, so continuous scanning results in a faster decay of the poled domain. The obtained effects are attributed to a decrease of the induced polarization and backswitching of the polarized area under the action of the depolarization field.
Discovery of circulating proteins associated to knee radiographic osteoarthritis
Authors: Lourido Lucía , Ayoglu Burcu , Fernández-Tajes Juan , Oreiro Natividad , Henjes Frauke , Hellström Cecilia , Schwenk Jochen M. , Ruiz-Romero Cristina , Nilsson Peter , Blanco Francisco J.
Published: March 2017

Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.
Lysophosphatidic acid counteracts glucagon-induced hepatocyte glucose production via STAT3
Authors: Taddeo Evan P. , Hargett Stefan R. , Lahiri Sujoy , Nelson Marin E. , Liao Jason A. , Li Chien , Slack-Davis Jill K. , Tomsig Jose L. , Lynch Kevin R. , Yan Zhen , Harris Thurl E. , Hoehn Kyle L.
Published: March 2017

Hepatic glucose production (HGP) is required to maintain normoglycemia during fasting. Glucagon is the primary hormone responsible for increasing HGP; however, there are many additional hormone and metabolic factors that influence glucagon sensitivity. In this study we report that the bioactive lipid lysophosphatidic acid (LPA) regulates hepatocyte glucose production by antagonizing glucagon-induced expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Treatment of primary hepatocytes with exogenous LPA blunted glucagon-induced PEPCK expression and glucose production. Similarly, knockout mice lacking the LPA-degrading enzyme phospholipid phosphate phosphatase type 1 (PLPP1) had a 2-fold increase in endogenous LPA levels, reduced PEPCK levels during fasting, and decreased hepatic gluconeogenesis in response to a pyruvate challenge. Mechanistically, LPA antagonized glucagon-mediated inhibition of STAT3, a transcriptional repressor of PEPCK. Importantly, LPA did not blunt glucagon-stimulated glucose production or PEPCK expression in hepatocytes lacking STAT3. These data identify a novel role for PLPP1 activity and hepatocyte LPA levels in glucagon sensitivity via a mechanism involving STAT3.
3D Printed Graphene Based Energy Storage Devices
Authors: Foster Christopher W. , Down Michael P. , Zhang Yan , Ji Xiaobo , Rowley-Neale Samuel J. , Smith Graham C. , Kelly Peter J. , Banks Craig E.
Published: March 2017

3D printing technology provides a unique platform for rapid prototyping of numerous applications due to its ability to produce low cost 3D printed platforms. Herein, a graphene-based polylactic acid filament (graphene/PLA) has been 3D printed to fabricate a range of 3D disc electrode (3DE) configurations using a conventional RepRap fused deposition moulding (FDM) 3D printer, which requires no further modification/ex-situ curing step. To provide proof-of-concept, these 3D printed electrode architectures are characterised both electrochemically and physicochemically and are advantageously applied as freestanding anodes within Li-ion batteries and as solid-state supercapacitors. These freestanding anodes neglect the requirement for a current collector, thus offering a simplistic and cheaper alternative to traditional Li-ion based setups. Additionally, the ability of these devices’ to electrochemically produce hydrogen via the hydrogen evolution reaction (HER) as an alternative to currently utilised platinum based electrodes (with in electrolysers) is also performed. The 3DE demonstrates an unexpectedly high catalytic activity towards the HER (−0.46 V vs. SCE) upon the 1000th cycle, such potential is the closest observed to the desired value of platinum at (−0.25 V vs. SCE). We subsequently suggest that 3D printing of graphene-based conductive filaments allows for the simple fabrication of energy storage devices with bespoke and conceptual designs to be realised.
Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells
Authors: Hicks Daniel F. , Goossens Nicolas , Blas-García Ana , Tsuchida Takuma , Wooden Benjamin , Wallace Michael C. , Nieto Natalia , Lade Abigale , Redhead Benjamin , Cederbaum Arthur I , Dudley Joel T. , Fuchs Bryan C. , Lee Youngmin A. , Hoshida Yujin , Friedman Scott L.
Published: March 2017

We have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human HSC line, TWNT-4. To identify proteins mediating apigenin’s effect, we next overlapped a 122-gene signature unique to HSCs with a list of 160 genes encoding proteins that are known to interact with apigenin, which identified C1QTNF2, encoding for Complement C1q tumor necrosis factor-related protein 2, a secreted adipocytokine with metabolic effects in liver. To validate its disease relevance, C1QTNF2 expression is reduced during hepatic stellate cell activation in culture and in a mouse model of alcoholic liver injury in vivo, and its expression correlates with better clinical outcomes in patients with hepatitis C cirrhosis (n = 216), suggesting it may have a protective role in cirrhosis progression.These findings reinforce the value of computational approaches to drug discovery for hepatic fibrosis, and identify C1QTNF2 as a potential mediator of apigenin’s anti-fibrotic activity.
The developmental and environmental regulation of gravitropic setpoint angle in Arabidopsis and bean
Authors: Roychoudhry Suruchi , Kieffer Martin , Del Bianco Marta , Liao Che-Yang , Weijers Dolf , Kepinski Stefan
Published: March 2017

Root and shoot branches are major determinants of plant form and critical for the effective capture of resources below and above ground. These branches are often maintained at specific angles with respect to gravity, known as gravitropic set point angles (GSAs). We have previously shown that the mechanism permitting the maintenance of non-vertical GSAs is highly auxin-dependent and here we investigate the developmental and environmental regulation of root and shoot branch GSA. We show that nitrogen and phosphorous deficiency have opposing, auxin signalling-dependent effects on lateral root GSA in Arabidopsis: while low nitrate induces less vertical lateral root GSA, phosphate deficiency results in a more vertical lateral root growth angle, a finding that contrasts with the previously reported growth angle response of bean adventitious roots. We find that this root-class-specific discrepancy in GSA response to low phosphorus is mirrored by similar differences in growth angle response to auxin treatment between these root types. Finally we show that both shaded, low red/far-red light conditions and high temperature induce more vertical growth in Arabidopsis shoot branches. We discuss the significance of these findings in the context of efforts to improve crop performance via the manipulation of root and shoot branch growth angle.
SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules
Authors: Daina Antoine , Michielin Olivier , Zoete Vincent
Published: March 2017

To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.
Wavelength tunable InGaN/GaN nano-ring LEDs via nano-sphere lithography
Authors: Wang Sheng-Wen , Hong Kuo-Bin , Tsai Yu-Lin , Teng Chu-Hsiang , Tzou An-Jye , Chu You-Chen , Lee Po-Tsung , Ku Pei-Cheng , Lin Chien-Chung , Kuo Hao-Chung
Published: March 2017

In this research, nano-ring light-emitting diodes (NRLEDs) with different wall width (120 nm, 80 nm and 40 nm) were fabricated by specialized nano-sphere lithography technology. Through the thinned wall, the effective bandgaps of nano-ring LEDs can be precisely tuned by reducing the strain inside the active region. Photoluminescence (PL) and time-resolved PL measurements indicated the lattice-mismatch induced strain inside the active region was relaxed when the wall width is reduced. Through the simulation, we can understand the strain distribution of active region inside NRLEDs. The simulation results not only revealed the exact distribution of strain but also predicted the trend of wavelength-shifted behavior of NRLEDs. Finally, the NRLEDs devices with four-color emission on the same wafer were demonstrated.
Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma
Authors: Chow Yock Ping , Tan Lu Ping , Chai San Jiun , Abdul Aziz Norazlin , Choo Siew Woh , Lim Paul Vey Hong , Pathmanathan Rajadurai , Mohd Kornain Noor Kaslina , Lum Chee Lun , Pua Kin Choo , Yap Yoke Yeow , Tan Tee Yong , Teo Soo Hwang , Khoo Alan Soo-Beng , Patel Vyomesh
Published: March 2017

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.
Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye
Authors: Giannaccini Martina , Pedicini Lucia , De Matienzo Guglielma , Chiellini Federica , Dente Luciana , Raffa Vittoria
Published: March 2017

Despite the higher rate of blindness due to population aging, minimally invasive and selective drug delivery to the eye still remains an open challenge, especially in the posterior segment. The retina, the retinal pigment epithelium (RPE) and the choroid are posterior segment cell layers, which may be affected by several diseases. In particular, damages to the choroid are associated with poor prognosis in the most severe pathologies. A drug delivery approach, able to target the choroid, is still missing. Recently, we demonstrated that intravitreally injected magnetic nanoparticles (MNP) are able to rapidly and persistently localise within the RPE in an autonomous manner. In this work we functionalised the MNP surface with the vascular endothelial growth factor, a bioactive molecule capable of transcytosis from the RPE towards more posterior layers. Such functionalisation successfully addressed the MNPs to the choroid, while MNP functionalised with a control polypeptide (poly-L-lysine) showed the same localisation pattern of the naked MNP particles. These data suggest that the combination of MNP with different bioactive molecules could represent a powerful strategy for cell-specific targeting of the eye posterior segment.
Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation
Authors: Li Jiejing , Qu Jiagui , Shi Yu , Perfetto Mark , Ping Zhuxian , Christian Laura , Niu Hua , Mei Shuting , Zhang Qin , Yang Xiangcai , Wei Shuo
Published: March 2017

Malignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo. Treatment of the U251 glioma cells with NA in vitro results in reduced invasion, which is accompanied by a loss of mesenchymal phenotype and an increase in cell-cell adhesion. At the molecular level, transcription of the adherens junction protein E-cadherin is upregulated, leading to accumulation of E-cadherin protein at the cell-cell boundary. This can be attributed to NA’s ability to facilitate the ubiquitination and degradation of Snail1, a transcription factor that represses E-cadherin expression. Similarly, NA transiently inhibits neural crest migration in Xenopus embryos in a Snail1-dependent manner, indicating that the mechanism of action for NA in cell migration is evolutionarily conserved. We further show that NA injection blocks the infiltration of tumor cells into the adjacent brain tissues and improves animal survival in a rat model of glioma. These results suggest that NA treatment may be developed into a potential therapy for malignant glioma.
Phthalocyanine Doped Metal Oxide Nanoparticles on Multiwalled Carbon Nanotubes Platform for the detection of Dopamine
Authors: Mphuthi Ntsoaki G. , Adekunle Abolanle S. , Fayemi Omolola E. , Olasunkanmi Lukman O. , Ebenso Eno E.
Published: March 2017

The electrocatalytic properties of metal oxides (MO = Fe3O4, ZnO) nanoparticles doped phthalocyanine (Pc) and functionalized MWCNTs, decorated on glassy carbon electrode (GCE) was investigated. Successful synthesis of the metal oxide nanoparticles and the MO/Pc/MWCNT composite were confirmed using UV-Vis, EDX, XRD and TEM techniques. Successful modification of GCE with the MO and their composite was also confirmed using cyclic voltammetry (CV) technique. GCE-MWCNT/ZnO/29H,31H-Pc was the best electrode towards DA detection with very low detection limit (0.75 μM) which compared favourably with literature, good sensitivity (1.45 μA/μM), resistance to electrode fouling, and excellent ability to detect DA without interference from AA signal. Electrocatalytic oxidation of DA on GCE-MWCNT/ZnO/29H,31H-Pc electrode was diffusion controlled but characterized with some adsorption of electro-oxidation reaction intermediates products. The fabricated sensors are easy to prepare, cost effective and can be applied for real sample analysis of dopamine in drug composition. The good electrocatalytic properties of 29H,31H-Pc and 2,3-Nc were related to their (quantum chemically derived) frontier molecular orbital energies and global electronegativities. The better performance of 29H,31H-Pc than 2,3-Nc in aiding electrochemical oxidation of DA might be due to its better electron accepting ability, which is inferred from its lower ELUMOand higher χ.
Physico-mechanical and morphological features of zirconia substituted hydroxyapatite nano crystals
Authors: Mansour S. F. , El-dek S. I. , Ahmed M. K.
Published: March 2017

Zirconia doped Hydroxyapatite (HAP) nanocrystals [Ca10(PO4)6−x(ZrO2)x(OH)2]; (0 ≤ x ≤ 1 step 0.2) were synthesized using simple low cost facile method. The crystalline phases were examined by X-ray diffraction (XRD). The crystallinity percentage decreased with increasing zirconia content for the as-synthesized samples. The existence of zirconia as secondary phase on the grain boundaries; as observed from scanning electron micrographs (FESEM); resulted in negative values of microstrain. The crystallite size was computed and the results showed that it increased with increasing annealing temperature. Thermo-gravimetric analysis (TGA) assured the thermal stability of the nano crystals over the temperature from room up to 1200 °C depending on the zirconia content. The corrosion rate was found to decrease around 25 times with increasing zirconia content from x = 0.0 to 1.0. Microhardness displayed both compositional and temperature dependence. For the sample (x = 0.6), annealed at 1200 °C, the former increased up to 1.2 times its original value (x = 0.0).