bluuebunny/crossref_metadata_2025 huggingface dataset:
Fault welding by pseudotachylyte formation
Authors: Mitchell Thomas M. , Toy Virginia , Di Toro Giulio , Renner Jörg , Sibson Richard H.
Published: October 2016

During earthquakes, melt produced by frictional heating can accumulate on slip surfaces and dramatically weaken faults by melt lubrication. Once seismic slip slows and arrests, the melt cools and solidifies to form pseudotachylytes, the presence of which is commonly used by geologists to infer earthquake slip on exhumed ancient faults. Field evidence suggests that solidified melts may weld seismic faults, resulting in subsequent seismic ruptures propagating on neighboring pseudotachylyte-free faults or joints and thus leading to long-term fault slip delocalization for successive ruptures. We performed triaxial deformation experiments on natural pseudotachylyte-bearing rocks, and show that cooled frictional melt effectively welds fault surfaces together and gives faults cohesive strength comparable to that of an intact rock. Consistent with the field-based speculations, further shear is not favored on the same slip surface, but subsequent failure is accommodated on a new subparallel fault forming on an off-fault preexisting heterogeneity. A simple model of the temperature distribution in and around a pseudotachylyte following slip cessation indicates that frictional melts cool to below their solidus in tens of seconds, implying strength recovery over a similar time scale.
Clockwise rotation of the entire Oman ophiolite occurred in a suprasubduction zone setting
Authors: Morris Antony , Meyer Matthew , Anderson Mark W. , MacLeod Christopher J.
Published: October 2016

The Oman ophiolite provides a natural laboratory for understanding oceanic lithospheric processes. Previous paleomagnetic and structural investigations have been used to support a model involving rotation of the ophiolite during formation at a mid-oceanic microplate. However, recent geochemical evidence indicates that the ophiolite instead formed in a nascent forearc environment, opening the potential for alternative rotation mechanisms. Central to the conundrum is the contrast between ESE to SE magnetizations and NNW magnetizations from the northern and southern ophiolitic massifs, respectively, attributed previously to either differential tectonic rotations during spreading or complete emplacement-related remagnetization of the southern massifs. Here we report new paleomagnetic data from lower crustal rocks of the southern massifs that resolve this problem. Sampling of a continuous section in Wadi Abyad reveals ENE magnetizations in the dike rooting zone at the top of the lower crust that change systematically downwards to NNW directions in underlying foliated and layered gabbros. This is consistent only with remagnetization from the base upwards, replacing early remanences in layered and foliated gabbros completely but preserving original ENE magnetizations at higher levels. Comparison with new data from Wadi Khafifah provides a positive fold test that shows that this event occurred before late Campanian structural disruption of the regional orientation of the petrologic Moho. These data show that the entire ophiolite experienced large intraoceanic clockwise rotation prior to partial remagnetization, leading to a new tectonic model in which formation, rotation, and emplacement of the ophiolite are all linked to Late Cretaceous motion of Arabia and roll-back of the Oman subduction zone.
Snorting the clivus away: an extreme case of cocaine-induced midline destructive lesion
Authors: Molteni Marco , Saibene Alberto Maria , Luciano Ketty , Maccari Alberto
Published: October 2016

Cocaine is a drug with relevant socioeconomic and clinical implications, which is usually recreationally used for its stimulant effects. It is widely known that the habit of snorting cocaine is associated with a peculiar type of drug-induced chronic rhinitis, which leads to inflammation of the sinonasal mucosa, slowly progressing to a destruction of nasal, palatal and pharyngeal tissues. These characteristic lesions due to cocaine abuse are commonly called cocaine-induced midline destructive lesions (CIMDL). Diagnosis is not always straightforward, since various conditions, mainly vasculitis, might mimic this acquired condition. The extent of pharyngeal involvement varies, although often a prolonged abuse can trigger a progressive destruction of oral and nasal tissues, with development of infections and recurrent inflammation. Our article focuses on cocaine as a world health problem with important ear, nose and throat implications and discusses the difficulties in diagnosing and treating CIMDL, through a case report.
Evaluating a community-based exercise intervention with adults living with HIV: protocol for an interrupted time series study
Authors: O'Brien Kelly K , Bayoumi Ahmed M , Solomon Patricia , Tang Ada , Murzin Kate , Chan Carusone Soo , Zobeiry Mehdi , Nayar Ayesha , Davis Aileen M
Published: October 2016

Introduction

Our aim was to evaluate a community-based exercise (CBE) intervention with the goal of reducing disability and enhancing health for community-dwelling people living with HIV (PLWH).

Methods and analysis

We will use a mixed-methods implementation science study design, including a prospective longitudinal interrupted time series study, to evaluate a CBE intervention with PLWH in Toronto, Canada. We will recruit PLWH who consider themselves medically stable and safe to participate in exercise. In the baseline phase (0–8 months), participants will be monitored bimonthly. In the intervention phase (8–14 months), participants will take part in a 24-week CBE intervention that includes aerobic, resistance, balance and flexibility exercise at the YMCA 3 times per week, with weekly supervision by a fitness instructor, and monthly educational sessions. In the follow-up phase (14–22 months), participants will be encouraged to continue to engage in unsupervised exercise 3 times per week.Quantitative assessment: We will assess cardiopulmonary fitness, strength, weight, body composition and flexibility outcomes followed by the administration of self-reported questionnaires to assess disability and contextual factor outcomes (coping, mastery, stigma, social support) bimonthly. We will use time series regression analysis to determine the level and trend of outcomes across each phase in relation to the intervention.Qualitative assessment: We will conduct a series of face-to-face interviews with a subsample of participants and recreation providers at initiation, midpoint and completion of the 24-week CBE intervention. We will explore experiences and anticipated benefits with exercise, perceived impact of CBE for PLWH and the strengths and challenges of implementing a CBE intervention. Interviews will be audio recorded and analysed thematically.

Ethics and dissemination

Protocol approved by the University of Toronto HIV/AIDS Research Ethics Board. Knowledge translation will occur with stakeholders in the form of presentations and publications in open access peer-reviewed journals.

Trial registration number

NCT02794415; Pre-results.
Ranking regional drowning mortality rates: population-based versus aquatic area-based rate
Authors: Wang Chien-Hsing , Hsieh Wan-Hua , Lee Jo-Chi , Wu Hsin-Min , Lu Tsung-Hsueh
Published: October 2016

Population, the most often used denominator in calculating drowning mortality rate, might not be a good measure of risk exposure. In this study, we sought to compare the rankings of township drowning mortality according to population-based rates with those according to aquatic area-based rates in Taitung County, Taiwan. The township with the highest mortality rate using population as the denominator (deaths per 100 000 persons) was Changbin (32.3) followed by Lanyu (22.4), Donghe (19.6) and Chenggong (18.0). On the other hand, the township with the leading mortality rate using aquatic area as the denominator (deaths per 100 000 km2) was Lanyu (353) followed by Lyudao (307), Chenggong (282) and Taitung City (219). Taitung City ranked 10th according to the population-based rate, but ranked 4th according to the aquatic area-based rate. In conclusion, rankings of regional drowning mortality rates using aquatic area as the denominator differ from those using population as the denominator.
Subsequent Injury Study (SInS): Improving outcomes for injured New Zealanders
Authors: Derrett Sarah , Harcombe Helen , Wyeth Emma , Davie Gabrielle , Samaranayaka Ari , Hansen Paul , Hall Gill , Cameron Ian D , Gabbe Belinda , Powell Denise , Sullivan Trudy , Wilson Suzanne , Barson Dave
Published: October 2016

Background

Subsequent injury (SI) is a major contributor to disability and costs for individuals and society.

Aim

To identify modifiable risk factors predictive of SI and SI health and disability outcomes and costs.

Objectives

To (1) describe the nature of SIs reported to New Zealand's no-fault injury insurer (the Accident Compensation Corporation (ACC)); (2) identify characteristics of people underaccessing ACC for SI; (3) determine factors predicting or protecting against SI; and (4) investigate outcomes for individuals, and costs to society, in relation to SI.

Design

Prospective cohort study.

Methods

Previously collected data will be linked including data from interviews undertaken as part of the earlier Prospective Outcomes of Injury Study (POIS), ACC electronic data and national hospitalisation data about SI. POIS participants (N=2856, including 566 Māori) were recruited via ACC's injury register following an injury serious enough to warrant compensation entitlements. We will examine SI over the following 24 months for these participants using descriptive and inferential statistics including multivariable generalised linear models and Cox's proportional hazards regression.

Discussion

Subsequent Injury Study (SInS) will deliver information about the risks, protective factors and outcomes related to SI for New Zealanders. As a result of sourcing injury data from New Zealand's ‘all injury’ insurer ACC, SInS includes people who have been hospitalised and not hospitalised for injury. Consequently, SInS will provide insights that are novel internationally as other studies are usually confined to examining trauma registries, specific injuries or injured workers who are covered by a workplace insurer rather than a ‘real-world’ injury population.
Low-dose intravenous tissue plasminogen activator for acute ischaemic stroke: an alternative or a new standard?
Authors: Dong Yi , Cao Wenjie , Cheng Xin , Fang Kun , Wu Fei , Yang Lumeng , Xie Yanan , Dong Qiang
Published: October 2016

Background

With the recent publication of a large clinical trial on the use of a lower dose of intravenous (IV) tissue plasminogen activator (tPA) for acute ischaemic stroke (AIS), the concept of using a different dose has been debated. We intend to review the literature on using a lower dose of IV tPA and gain a better understanding of the impact of different IV doses on the treatment of patients with AIS.

Methods

A comprehensive literature search of the related topics in PubMed, EMBASE, Web of Science and MEDLINE was carried out. Key words used include low dose IV tPA, thrombolysis, Alteplace and tPA for AIS. Findings were tabulated according to the size of the cohort studied, outcome, adverse event and level of evidence. The results of all studies using lower doses were analysed for efficacy and adverse events.

Results

From 1992 to 2016, there were 23 trials that included 10 950 patients published on the use of lower doses of IV tPA for AIS. Doses ranged from 0.5, 0.6, 0.75 to 0.85 mg/kg. Most were observational, retrospective and registry studies. One was a prospective open-label randomised controlled trial. 13 trials combined lower doses of IV tPA with a glycoprotein IIb/IIIa inhibitor or thrombectomy. Patients treated with lower doses of IV tPA showed a trend of lower rate of symptomatic intracranial haemorrhage and mortality at 3 months but slightly more disability.

Conclusions

Lower doses of IV tPA showed less haemorrhagic events but were not more effective compared with the standard dose. The optimal low dose of IV tPA remains unclear. Patients with AIS with a high risk of developing sypmtomatic intracranial haemorrhage might benefit from lower dose IV tPA, such as 0.6 mg/kg.
Genetic diversity of bovine viral diarrhea viruses from the Galicia region of Spain
Authors: Factor C. , Yus E. , Eiras C. , Sanjuan M. L. , Cerviño M. , Arnaiz I. , Diéguez F. J.
Published: October 2016

This study examined the frequency and diversity of bovine viral diarrhoea viruses (BVDVs) infecting cattle in Galicia (northwestern Spain). A total of 86 BVDV strains were typed in samples of serum from 79 persistently infected animals and 3 viraemic animals and of abomasal fluid from 4 fetuses. Samples came from 73 farms participating in a voluntary BVDV control programme. Typing was based on a 288‐bp sequence from the 5′ untranslated region amplified using primers 324 and 326. Of the 86 strains, 85 (98.8 per cent) belonged to species BVDV‐1 and 1 (1.2 per cent) belonged to BVDV‐2; 73 strains (84.9 per cent) were typed as BVDV‐1b, 2 as BVDV‐1e and 6 as BVDV‐1d. One strain each was typed as belonging to 1a, 1h, 1k and 1l. The sole BVDV‐2 strain was classified as 2a. These results identify BVDV‐1b as the predominant species, and they indicate the presence of viral types not previously described anywhere in Spain. This is also the first report of BVDV‐2 in Galicia and only the second report of BVDV‐2 in Spain.
Ten‐minute chat
Authors: Leonard Steve
Published: October 2016

TV vet Steve Leonard is a patron of the Painted Dog Conservation UK charity. From time to time he leads conservation safaris to the charity's centre in Hwange National Park in Zimbabwe.
Numerical modelling of pipelines with air pockets and air valves
Authors: Fuertes-Miquel Vicente S. , López-Jiménez P. Amparo , Martínez-Solano F. Javier , López-Patiño Gonzalo
Published: October 2016

This work considers the behaviour of air inside pipes when the air is expelled through air valves. Generally, the air shows isothermal behaviour. Nevertheless, when the transient is very fast, it shows adiabatic behaviour. In a real installation, an intermediate evolution between these two extreme conditions occurs. Thus, it is verified that the results vary significantly depending on the hypothesis adopted. To determine the pressure of the air pocket, the most unfavourable hypothesis (isothermal behaviour) is typically adopted. Nevertheless, from the perspective of the water hammer that takes place when the water column arrives at the air valve and abruptly closes, the most unfavourable hypothesis is the opposite (adiabatic behaviour). In this case, the residual velocity with which the water arrives at the air valve is higher, and, consequently, the water hammer generated is greater.
de Sitter space–time as a natural superconductor
Authors: Momeni Davood , Myrzakulov Ratbay , Zaz Zaid
Published: October 2016

Motivated by the studies done on magnetically induced superconductivity on QCD vacuum we propose that de Sitter space–time is a natural superconductor. This is due to the occurrence of spinor condensation. We provide a framework for joining the curvature of space–time with superconductor processes. We demonstrate that for a critical value of de Sitter radius unstable tachyon modes exist showing the existence of a superconducting phase.
Collapse and expansion of plane symmetric charged anisotropic source
Authors: Abbas G. , Shah S.M. , Zubair M.
Published: October 2016

In this paper, we have investigated the final evolutionary stages of charged non-static plane symmetric anisotropic source. To this end, we have solved the Einstein–Maxwell field equations with the charged plane symmetric source. We have found that vanishing of radial heat flux in the gravitating source provides the parametric form of the metric functions. The new form of the metric functions can generate a class of physically acceptable solutions depending on the choice parameter. These solutions may be classified as expanding or collapsing solutions with the particular values of generating parameter. The gravitational collapse in this case ends with the formation of single apparent horizon while there exists two such horizons in the case of charged spherical anisotropic source.
Archaeology and Contemporary Warfare
Authors: Pollock Susan
Published: October 2016

In the contemporary world, archaeology has become drawn, sometimes in dramatic fashion, into the violence of war. Archaeologists have taken part in monitoring and attempting to protect sites, museums, and monuments. However, they have engaged to a lesser extent with the underlying connections between damage to and destruction of archaeological remains and the reasons why archaeology has become increasingly both a target and a weapon of war. To highlight the complex intertwining of archaeology and war, this review examines the relationships among archaeologists' conceptions of their profession, the spiraling commodification of remains of the past, understandings and practices of cultural heritage, and the willful destruction of archaeological sites and objects, with a focus on Western Asia.
Some Recent Trends in the Linguistic Anthropology of Native North America
Authors: Kroskrity Paul V.
Published: October 2016

Although the languages of Native North America and the linguistic communities that spoke these languages once provided the key data for American anthropology's early agenda under Boas, linguistic anthropologists continue their study in a manner inflected to contemporary political economic realities and theoretical concerns. One area of scholarship that displays some continuity with earlier research is the study of Native American place-names, but even here contemporary researchers have explored the ethnographic surround of naming practices, including the multilingualism and multiculturalism of today's indigenous communities. Other research topics that have had less precedent include verbal art, language ideologies, and linguistic racism. Recent research in Native North American verbal art has advanced the appreciation of indigenous poetics but also developed a “critical” ethnopoetics that attends to a larger political economic context. Recent research on language ideologies has explored such topics as new patterns of language and identity and the role of ideologies in language revitalization.
Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to a potential antifibrotic therapy
Authors: Karsdal Morten A. , Henriksen Kim , Nielsen Mette Juul , Byrjalsen Inger , Leeming Diana J. , Gardner Stephen , Goodman Zachary , Patel Keyur , Krag Aleksander , Christiansen Claus , Schuppan Detlef
Published: October 2016

There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic trial of the glitazone farglitazar in patients with advanced hepatitis C, with matched follow-up liver biopsies, and from a phase III study of balaglitazone in patients with late-stage Type 2 diabetes (BALLET study) were analyzed for serological Pro-C3 levels in conjunction with other disease parameters. In the farglitazar study, a predefined cutoff value for Pro-C3 as a selection criterion led to the identification of subjects who 1) progressed by histological scores and 2) responded to therapy, as documented by attenuated fibrosis in liver biopsies. In the BALLET trial, subjects with the highest tertile of Pro-C3 levels responded to balaglitazone with reductions in levels of alanine aminotransferase and Pro-C3, as well as improved insulin sensitivity and lipid profile. Elevated Pro-C3 levels are indicative of active fibrogenesis and structural progression of fibrosis, and it can potentially identify patients most likely to benefit from antimetabolic and antifibrotic treatments. Serum Pro-C3 may facilitate patient selection and could help to speed up antifibrotic drug development and validation.
IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity
Authors: Chiang Sarah , Weigelt Britta , Wen Huei-Chi , Pareja Fresia , Raghavendra Ashwini , Martelotto Luciano G. , Burke Kathleen A. , Basili Thais , Li Anqi , Geyer Felipe C. , Piscuoglio Salvatore , Ng Charlotte K.Y. , Jungbluth Achim A. , Balss Jörg , Pusch Stefan , Baker Gabrielle M. , Cole Kimberly S. , von Deimling Andreas , Batten Julie M. , Marotti Jonathan D. , Soh Hwei-Choo , McCalip Benjamin L. , Serrano Jonathan , Lim Raymond S. , Siziopikou Kalliopi P. , Lu Song , Liu Xiaolong , Hammour Tarek , Brogi Edi , Snuderl Matija , Iafrate A. John , Reis-Filho Jorge S. , Schnitt Stuart J.
Published: October 2016

Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1. One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation. Functional studies demonstrated that IDH2 and PIK3CA hotspot mutations are likely drivers of SPCRP, resulting in its reversed nuclear polarization phenotype. Our results offer a molecular definition of SPCRP as a distinct breast cancer subtype. Concurrent IDH2 and PIK3CA mutations may help diagnose SPCRP and possibly direct effective treatment. Cancer Res; 76(24); 7118–29. ©2016 AACR.
Preclinical Evidence That 3′-Deoxy-3′-[18F]Fluorothymidine PET Can Visualize Recovery of Hematopoiesis after Gemcitabine Chemotherapy
Authors: Schelhaas Sonja , Held Annelena , Bäumer Nicole , Viel Thomas , Hermann Sven , Müller-Tidow Carsten , Jacobs Andreas H.
Published: October 2016

Molecular imaging with the PET tracer 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) allows assessment of the proliferative state of organs in vivo. Although used primarily in the oncology clinic, it can also shed light on the proliferation of other tissues, as demonstrated here for monitoring hematopoietic organs that recover after myelosuppressive chemotherapy. In the NMRI nude mouse model, we observed up to a 4.5-fold increase in [18F]FLT uptake in bone marrow and spleen on days 2, 3, and 5 after treatment with gemcitabine, a chemotherapeutic agent that is powerfully myelosuppressive in the model. Specifically, we observed (i) a reduced spleen weight; (ii) reduced bone marrow cell counts and proliferation (BrdUrd flow cytometry, spleen IHC; 6 hours/day 1); and (iii) reduced leukocytes in peripheral blood (day 5). In conclusion, our results show how [18F]FLT PET can provide a powerful tool to noninvasively visualize the proliferative status of hematopoietic organs after myelosuppressive therapy. Cancer Res; 76(24); 7089–95. ©2016 AACR.
Glucose Metabolism Reprogrammed by Overexpression of IKKϵ Promotes Pancreatic Tumor Growth
Authors: Zubair Haseeb , Azim Shafquat , Srivastava Sanjeev Kumar , Ahmad Aamir , Bhardwaj Arun , Khan Mohammad Aslam , Patel Girijesh Kumar , Arora Sumit , Carter James Elliot , Singh Seema , Singh Ajay Pratap
Published: October 2016

Aberrant expression of the kinase IKKϵ in pancreatic ductal adenocarcinoma (PDAC) has been associated with poor prognosis. In this study, we define a pathobiologic function for IKKϵ in reprogramming glucose metabolism and driving progression in PDAC. Silencing IKKϵ in PDAC cells, which overexpressed it endogenously, was sufficient to reduce malignant cell growth, clonogenic potential, glucose consumption, lactate secretion, and expression of genes involved in glucose metabolism, without impacting the basal oxygen consumption rate. IKKϵ silencing also attenuated c-Myc in a manner associated with diminished signaling through an AKT/GSK3β/c-MYC phosphorylation cascade that promoted MYC nuclear accumulation. In an orthotopic mouse model, IKKϵ-silenced PDAC exhibited a relative reduction in glucose uptake, tumorigenicity, and metastasis. Overall, our findings offer a preclinical mechanistic rationale to target IKKϵ to improve the therapeutic management of PDAC in patients. Cancer Res; 76(24); 7254–64. ©2016 AACR.
Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults
Authors: Howe Caitlin G. , Liu Xinhua , Hall Megan N. , Ilievski Vesna , Caudill Marie A. , Malysheva Olga , Lomax-Luu Angela M. , Parvez Faruque , Siddique Abu B. , Shahriar Hasan , Uddin Mohammad N. , Islam Tariqul , Graziano Joseph H. , Costa Max , Gamble Mary V.
Published: October 2016

Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation.

Methods: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs.

Results: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80).

Conclusions: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs.

Impact: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261–9. ©2016 AACR.
SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition
Authors: Talarico Cristina , Dattilo Vincenzo , D'Antona Lucia , Menniti Miranda , Bianco Cataldo , Ortuso Francesco , Alcaro Stefano , Schenone Silvia , Perrotti Nicola , Amato Rosario
Published: October 2016

The serum- and glucocorticoid-regulated kinase (SGK) family consists of three members, SGK1, SGK2 and SGK3, all displaying serine/threonine kinase activity and sharing structural and functional similarities with the AKT family of kinases. SGK1 was originally described as a key enzyme in the hormonal regulation of several ion channels and pumps. Over time, growing and impressive evidence has been accumulated, linking SGK1 to the cell survival, de-differentiation, cell cycle control, regulation of caspases, response to chemical, mechanical and oxidative injury in cancer models as well as to the control of mitotic stability. Much evidence shows that SGK1 is over-expressed in a variety of epithelial tumors. More recently, many contributions to the published literature demonstrate that SGK1 can mediate chemo-and radio-resistance during the treatment of various human tumors, both in vitro and in vivo. SGK1 appears therefore as a dirty player in the stress response to chemical and radio-agents, responsible of a selective advantage that favors the uncontrolled tumor progression and the selection of the most aggressive clones. The purpose of this review is the analysis of the literature describing SGK1 as central node of the cell resistance, and a summary of the possible strategies in the pharmacological targeting of SGK1.
Clinical Therapeutic Effects of Aspirin in Combination with Fufang Danshen Diwan, a Traditional Chinese Medicine Formula, on Coronary Heart Disease: A Systematic Review and Meta-Analysis
Authors: Huang Jianchun , Tang Xiaojun , Ye Fangxing , He Junhui , Kong Xiaolong
Published: October 2016

Background/Aims: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. Methods: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. Results: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD −1.12; 95% CI −1.49 to −0.76); 2) reduction of TG level (SMD −0.94; 95% CI −1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. Conclusion: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.
Toll-Like Receptor 3 Contributes to Wallerian Degeneration after Peripheral Nerve Injury
Authors: Lee Hyunkyoung , Baek Jiyeon , Min Hyunjung , Cho Ik-Hyun , Yu Seong-Woo , Lee Sung Joong
Published: October 2016

Objective: It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice. Methods: Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR. Results: In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo. Conclusion: These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves.
The Biological Impact of Genomic Diversity in Cervical Cancer Development
Authors: Mendes de Oliveira Cristina , Levi José Eduardo
Published: October 2016

Human papillomaviruses (HPVs) are the etiologic agents of cervical cancer, the unique human neoplasia that has one single necessary cause. The diversity of HPVs is well described, with 200 HPV types existing as distinct taxonomic units and each receiving an Arabic number. On a clinical basis, they are usually grouped by their site of occurrence and disease associations. Those types inhabiting the anogenital mucosa are more intensively studied and further divided into cancer-associated HPVs, which are termed ‘high risk', while those linked to benign proliferative lesions are assigned as ‘low risk'. HPV16 is responsible for approximately 50% of all ICC cases, and paradoxically is one of the most prevalent types among healthy women. Longitudinal studies have shown that when an incidental HPV16 infection becomes persistent it will result in an enhanced risk for the development of high-grade lesions. However, it is unknown why some persistent, HPV16 infections (or infections by other HR-HPV types) progress to CIN3+ while most clear spontaneously. Several epidemiological investigations have focused on cofactors, from the most obvious such as cigarette and other carcinogenic exposures, to coinfections by other STDs such as chlamydia, with no significant findings. Thus, the current focus is on genomic variation from both virus and host. Such studies have been potentialized by the enormous technical advances in nucleic acid sequencing, allowing this relationship to be broadly interrogated. Corroborating subgenomic data from decades ago, an association between HPV16 lineages and carcinogenesis is being revealed. However, this effect does not seem to apply across female populations from different continents/ethnicities, again highlighting a role played by HPV16 adaptation and evasion from the host over time.
Cardiac Hepcidin Expression Associates with Injury Independent of Iron
Authors: van Breda G. Fenna , Bongartz Lennart G. , Zhuang Wenqing , van Swelm Rachel P.L. , Pertijs Jeanne , Braam Branko , Cramer Maarten-Jan , Swinkels Dorine W. , Doevendans Pieter A. , Verhaar Marianne C. , Masereeuw Roos , Joles Jaap A. , Gaillard Carlo A.J.M.
Published: October 2016

Background: Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD). We hypothesized that cardiac hepcidin gene expression is induced by and regulated to severity of cardiac injury, either through direct (MI) or remote (CKD) stimuli, as well as through increased local iron content. Methods: Nine weeks after subtotal nephrectomy (SNX) or sham surgery (CON), rats were subjected to coronary ligation (CL) or sham surgery to realize 4 groups: CON, SNX, CL and SNX + CL. In week 16, the gene expression of hepcidin, iron and damage markers in cardiac and liver tissues was assessed by quantitative polymerase chain reaction and ferritin protein expression was studied by immunohistochemistry. Results: Cardiac hepcidin messenger RNA (mRNA) expression was increased 2-fold in CL (p = 0.03) and 3-fold in SNX (p = 0.01). Cardiac ferritin staining was not different among groups. Cardiac hepcidin mRNA expression correlated with mRNA expression levels of brain natriuretic peptide (β = 0.734, p < 0.001) and connective tissue growth factor (β = 0.431, p = 0.02). In contrast, liver hepcidin expression was unaffected by SNX and CL alone, while it had decreased 50% in SNX + CL (p < 0.05). Hepatic ferritin immunostaining was not different among groups. Conclusions: Our data indicate differences in hepcidin regulation in liver and heart and suggest a role for injury rather than iron as the driving force for cardiac hepcidin expression in renocardiac failure.
Elder Abuse in Nursing Homes: Do Special Care Units Make a Difference? A Secondary Data Analysis of the Swiss Nursing Homes Human Resources Project
Authors: Blumenfeld Arens Olivia , Fierz Katharina , Zúñiga Franziska
Published: October 2016

Background: In special care units (SCUs) for residents with advanced dementia, both personnel and organizations are adapted to the needs of residents. However, whether these adaptations have a preventive effect on elder abuse has not yet been explored. Objective: To describe the prevalence of observed emotional abuse, neglect, and physical abuse in Swiss nursing homes, to compare SCUs with non-SCUs concerning the frequency of observed emotional abuse, neglect, and physical abuse, and to explore how resident-related characteristics, staff outcomes/characteristics, and organizational/environmental factors relate to observed elder abuse. Methods: This is a secondary data analysis of the Swiss Nursing Homes Human Resources Project (SHURP), a cross-sectional multicenter study. Data were collected from 2012 to 2013 and are based on observed rather than perpetrated elder abuse. We performed multilevel mixed-effects logistic regressions taking into account the hierarchical structure of the data with personnel nested within units and facilities. Results: Of 4,599 care workers in 400 units and 156 facilities, 50.8% observed emotional abuse, 23.7% neglect, and 1.4% physical abuse. There was no significant difference between SCUs and non-SCUs regarding observed emotional abuse and neglect. Higher scores for ‘workload' and sexual aggression towards care workers were associated with higher rates of emotional abuse and neglect. Verbal and physical resident aggression, however, were only associated with higher rates of emotional abuse. Negative associations were found between ‘teamwork and resident safety climate' and both forms of abuse. Conclusion: Improving teamwork and the safety climate and reducing work stressors might be promising points of intervention to reduce elder abuse. More specific research about elder abuse in SCUs and the interaction between work climate and elder abuse is required.
Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature
Authors: Niida Yo , Sato Hitoshi , Ozaki Mamoru , Itoh Masatsune , Ikeno Kanju , Takase Etsuko
Published: October 2016

Less than 1% of the cases with Angelman syndrome (AS) are caused by chromosomal rearrangements. This category of AS is not well defined and may manifest atypical phenotypes. Here, we report a girl with AS due to der(13)t(13;15)(q14.1;q12)mat. SNP array detected the precise deletion/duplication points and the parental origin of the 15q deletion. Multicolor FISH confirmed a balanced translocation t(13;15)(q14.1;q12) in her mother. Her facial appearance showed some features of dup(13)(pter→q14). Also, she lacked the most characteristic and unique behavioral symptoms of AS, i.e., frequent laughter, happy demeanor, and easy excitability. A review of the literature indicated that AS cases caused by chromosomal rearrangements can be classified into 2 major categories and 4 groups. The first category is paternal uniparental disomy 15, which is subdivided into isodisomy by de novo rob(15;15) and heterodisomy caused by paternal translocation. The second category is the deletion of the AS locus due to maternal reciprocal translocation, which is subdivided into 2 groups associated with partial monosomy by 3:1 segregation and partial trisomy by adjacent-2 segregation. Classification into these categories facilitates the understanding of the mechanisms of chromosomal rearrangements and helps in accurate diagnosis and genetic counseling of these rare forms of AS.
The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives
Authors: Moris Demetrios , Kontos Michalis , Spartalis Eleftherios , Fentiman Ian S.
Published: October 2016

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable interest as potential chemopreventive agents. The aim of this review is to summarize the accumulated knowledge on the effect of NSAIDs on breast cancer incidence and natural history, and the underlying pathophysiology. NSAIDs mainly block inflammation by inhibiting cyclooxygenase enzymes, leading to lower prostaglandin synthesis. The latter has been reported to affect breast cancer risk through hormonal and inflammation-related pathways. Intensity, dose, frequency, duration, and timing of administration may also be significant. There is currently enough evidence to support a role of NSAIDs in breast cancer prevention and relapse, which deserves further large-scale experimental and clinical investigation.
Role of the Renal Microcirculation in Progression of Chronic Kidney Injury in Obesity
Authors: Chade Alejandro R. , Hall John E.
Published: October 2016

Background: Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular and renal diseases. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key Message: Microvascular (MV) disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The MV networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal MV injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal MV injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity.
Monocyte Conversion During Inflammation and Injury
Authors: Kratofil Rachel M. , Kubes Paul , Deniset Justin F.
Published: October 2016

Monocytes are circulating leukocytes important in both innate and adaptive immunity, primarily functioning in immune defense, inflammation, and tissue remodeling. There are 2 subsets of monocytes in mice (3 subsets in humans) that are mobilized from the bone marrow and recruited to sites of inflammation, where they carry out their respective functions in promoting inflammation or facilitating tissue repair. Our understanding of the fate of these monocyte subsets at the site of inflammation is constantly evolving. This brief review highlights the plasticity of monocyte subsets and their conversion during inflammation and injury.
Estimating the Population Impact of Lp(a) Lowering on the Incidence of Myocardial Infarction and Aortic Stenosis—Brief Report
Authors: Afshar Mehdi , Kamstrup Pia R. , Williams Ken , Sniderman Allan D. , Nordestgaard Børge G. , Thanassoulis George
Published: October 2016

Objective—

High lipoprotein(a) (Lp[a]) is the most common genetic dyslipidemia and is a causal factor for myocardial infarction (MI) and aortic stenosis (AS). We sought to estimate the population impact of Lp(a) lowering that could be achieved in primary prevention using the therapies in development.

Approach and Results—

We used published data from 2 prospective cohorts. High Lp(a) was defined as ≥50 mg/dL (≈20th percentile). Relative risk, attributable risk, the attributable risk percentage, population attributable risk, and the population attributable risk percentage were calculated as measures of the population impact. For MI, the event rate was 4.0% versus 2.8% for high versus low Lp(a) (relative risk, 1.46; 95% confidence interval [CI], 1.45–1.46). The attributable risk was 1.26% (95% CI, 1.24–1.27), corresponding to 31.3% (95% CI, 31.0–31.7) of the excess MI risk in those with high Lp(a). The population attributable risk was 0.21%, representing a population attributable risk percentage of 7.13%. For AS, the event rate was 1.51% versus 0.78% for high versus low Lp(a) (relative risk, 1.95; 95% CI, 1.94–1.97). The attributable risk was 0.74% (95% CI, 0.73–0.75), corresponding to 48.8% (95% CI, 48.3–49.3) of the excess AS risk in those with high Lp(a). The population attributable risk was 0.13%, representing a population attributable risk percentage of 13.9%. In sensitivity analyses targeting the top 10% of Lp(a), the population attributable risk percentage was 5.2% for MI and 7.8% for AS.

Conclusions—

Lp(a) lowering among the top 20% of the population distribution for Lp(a) could prevent 1 in 14 cases of MI and 1 in 7 cases of AS, suggesting a major impact on reducing the burden of cardiovascular disease. Targeting the top 10% could prevent 1 in 20 MI cases and 1 in 12 AS cases.
A New Diagnostic for Cyclic Wh-Movement: Discourse Particles in German Questions
Authors: Bayer Josef , Häussler Jana , Bader Markus
Published: October 2016

This article presents novel evidence for cyclic wh-movement. Two experiments show that the question-sensitive particle denn in German is more readily accepted when occurring in an independent interrogative clause than in a dependent clause embedded in a wh-question. Importantly, however, acceptance of denn in a dependent clause increases significantly when a wh-phrase has been moved out of that clause. We argue that denn is locally licensed by an interrogative Force head. In dependent clauses, this licensing can be mediated by long wh-movement leaving a transient representation of interrogative force in Spec,CP. Without such a mediating trace in Spec,CP, the licensing of the particle fails. In conclusion, denn in a dependent clause indicates cyclic wh-movement.