bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular events underlying maggot extract promoted rat in vivo and human in vitro skin wound healing
Authors: Li Pei‐Nan , Li Hong , Zhong Li‐Xia , Sun Yuan , Yu Li‐Jun , Wu Mo‐Li , Zhang Lin‐Lin , Kong Qing‐You , Wang Shou‐Yu , Lv De‐Cheng
Published: December 2014

Maggot extracts promote wound healing, but their bioactive part(s) and molecular effects on the regenerating tissues/cells remain largely unclear. These issues are addressed here by treating rat skin wounds, human keratinocyte line/HaCat and fibroblasts with maggot secretion/excretion, and the extracts of maggots without and with secretion/excretion. The wound closure rates, cell proliferation activities, and statuses of wound healing‐related signaling pathways (STAT3, Notch1, Wnt2, NF‐κB, and TGF‐beta/Smad3) and their downstream gene expression (c‐Myc, cyclin D1, and VEGF) are evaluated by multiple approaches. The results reveal that the maggot extracts, especially the one from the maggots without secretion/excretion, show the best wound healing‐promoting effects in terms of quicker wound closure rates and more rapid growth of keratinocytes and fibroblasts. Of the five signaling pathways checked, the ones mediated by TGF‐beta/Smad3, and STAT3 are activated in the untreated wounds and become further enhanced by the maggot extracts, accompanied with c‐Myc, VEGF, and cyclin D1 up‐regulation. Our results thus show (1) that both body extract and secretion/excretion of maggots contain favorable wound healing elements and (2) that the enhancement of TGF‐beta/Smad3 and STAT3 signaling activities may be the main molecular effects of maggot extracts on the wound tissues.
Meta‐analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood
Authors: Harris Donald G. , Quinn Kevin J. , French Beth M. , Schwartz Evan , Kang Elizabeth , Dahi Siamak , Phelps Carol J. , Ayares David L. , Burdorf Lars , Azimzadeh Agnes M. , Pierson Richard N.
Published: December 2014

Background

Genetically modified pigs are a promising potential source of lung xenografts. Ex vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series.

Methods

Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had one genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 h of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype.

Results

Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 h generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO‐1, hCD55, or hEPCR were associated with improved survival. hTBM, HLA‐E, and hCD39 were associated with no significant effect on the primary outcome.

Conclusion

This meta‐analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway‐specific injury and explore why some genes apparently exhibit neutral (hTBM, HLA‐E) or inconclusive (CD39) effects, GalTKO, hCD46, HO‐1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival.
Study on contact distortion during high aspect ratio contact SiO2 etching
Authors: Kim Jong Kyu , Lee Sung Ho , Cho Sung Il , Yeom Geun Young
Published: December 2014

As pattern density is increased in semiconductor integrated circuits (ICs) and pattern sizes are decreased to nanometer scale, high aspect ratio contact etching has become one of the most difficult processes in nanoscale IC fabrication. The increase in aspect ratio of the contact oxide etching raises problems such as low mask selectivity, microloading, pattern degradation, and etch stops. In this study, the authors investigated the effect of various oxide etch conditions such as mask materials, mask thickness, and oxide etch processes, on contact profile degradation. The results showed that greater contact pattern distortion occurred as the aspect ratio of the etched oxide was increased. The use of amorphous carbon instead of amorphous silicon as the etch mask, and the use of a more carbon-rich gas composition, lessened pattern distortion. The polymer deposited at the interface between the mask layer and the oxide layer appeared to significantly affect the degree of contact pattern distortion. By adding an in-situ polymer removal step during the overetch of a multistep contact oxide etch process with a 20:1 aspect ratio, about a 7% improvement in pattern distortion could be obtained without changing other conditions.
PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis
Authors: Coleman M. Teresa , Chen Ray Y. , Lee Myungsun , Lin Philana Ling , Dodd Lori E. , Maiello Pauline , Via Laura E. , Kim Youngran , Marriner Gwendolyn , Dartois Veronique , Scanga Charles , Janssen Christopher , Wang Jing , Klein Edwin , Cho Sang Nae , Barry Clifton E. , Flynn JoAnne L.
Published: December 2014

PET/CT imaging in macaques and humans with TB shows a beneficial therapeutic response to linezolid and a new oxazolidinone antibiotic, AZD5847.
Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the
Mycobacterium
Neighborhood
Authors: Pope Welkin H. , Jacobs-Sera Deborah , Russell Daniel A. , Rubin Daniel H. F. , Kajee Afsana , Msibi Zama N. P. , Larsen Michelle H. , Jacobs William R. , Lawrence Jeffrey G. , Hendrix Roger W. , Hatfull Graham F.
Published: December 2014

Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using
Mycobacterium smegmatis
mc
2
155 as a host. Patience has genomic features distinct from its
M. smegmatis
host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in
M. smegmatis
. Nonetheless, it propagates well in
M. smegmatis
, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of
M. smegmatis
presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.

IMPORTANCE
The mycobacteriophage Patience genome has a notably lower GC content (50.3%) than its
Mycobacterium smegmatis
host (67.4%) and has markedly different codon usage biases. The viral genome has an abundance of codons that are rare in the host and are decoded by wobble tRNA pairing, although the phage grows well and expression of most of the genes is detected by mass spectrometry. Patience thus has the genomic profile of a virus that evolved primarily in one type of host genetic landscape (moderate-GC bacteria) but has found its way into a distinctly different high-GC environment. Although Patience genes are ill matched to the host expression apparatus, this is of little functional consequence and has not evidently imposed a barrier to migration across the microbial landscape. Interestingly, comparison of expression levels and codon usage profiles reveals evidence of codon selection as the genome evolves and adapts to its new environment.
Partners for the optimal organisation of the healthcare continuum for high users of health and social services: protocol of a developmental evaluation case study design
Authors: Hudon Catherine , Chouinard Maud-Christine , Couture Martine , Brousselle Astrid , Couture Eva Marjorie , Dubois Marie-France , Fortin Martin , Freund Tobias , Loignon Christine , Mireault Jean , Pluye Pierre , Roberge Pasquale , Rodriguez Charo
Published: December 2014

Introduction

Case management allows us to respond to the complex needs of a vulnerable clientele through a structured approach that promotes enhanced interaction between partners. Syntheses on the subject converge towards a need for a better description of the relationships between programmes and their local context, as well as the characteristics of the clienteles and programmes that contribute to positive impacts. The purpose of this project is thus to describe and evaluate the case management programmes of four health and social services centres in the Saguenay-Lac- Saint-Jean region of Québec, Canada, in order to inform their improvement while creating knowledge on case management that can be useful in other contexts.

Methods and analysis

This research relies on a multiple embedded case study design based on a developmental evaluation approach. We will work with the case management programme for high users of hospital services of each centre. Three different units of analysis will be interwoven to obtain an in-depth understanding of each case, that is: (1) health and social services centre and local services network, (2) case management programme and (3) patients who are high users of services. Two strategies for programme evaluation (logic models and implementation analysis) will guide the mixed data collection based on qualitative and quantitative methods. This data collection will rely on: (1) individual interviews and focus groups; (2) participant observation; (3) document analysis; (4) clinical and administrative data and (5) questionnaires. Description and comparison of cases, and integration of qualitative and quantitative data will be used to guide the data analysis.

Ethics and dissemination

The study protocol was approved by the Ethics Research Boards of the four health and social services centres (HSSCs) involved. Findings will be disseminated by publications in peer-reviewed journals, conferences, and policy and practice partners in local and national government.
Children who leave the emergency department without being seen: a retrospective case note review
Authors: Sparrow Nicola , Pestell Trudie , Clancy Mike
Published: December 2014

Introduction

Children who attend an emergency department and then leave without being seen (LWBS) are a major concern as they are a potentially vulnerable group who may come to harm through failure to provide a timely and accessible service.

Objectives

We wished to establish the size of this population and importantly what subsequently happened to them over the following 7 days from their initial attendance, and the relevance of the College of Emergency Medicine LWBS Quality Indicator (QI 4) to this group.

Methods

A retrospective case note review over 6 months of all paediatric attendances who LWBS.

Setting

Southampton Paediatric Emergency Department.

Results

During a 6-month study period, 10 795 attended, of which 544 (5%) LWBS. 12.6% (69/544) reattended over the next 7 days, of which 14 were admitted, 7 for <12 h.

Conclusions

The majority who LWBS do so during peak times. Very few paediatric patients who LWBS then reattended required admission for >12 h (7/544, 1.3%). The rate of reattendance of those who LWBS and review of their case notes is potentially more valuable than the LWBS rate alone.
Antibiotic susceptibility of bacterial isolates from 502 dogs with respiratory signs
Authors: Rheinwald M. , Hartmann K. , Hähner M. , Wolf G. , Straubinger R. K. , Schulz B.
Published: December 2014

The aim of this study was to investigate the prevalence of bacterial species isolated from bronchoalveolar lavage fluid (BALF) samples taken from dogs with respiratory signs and to determine their antibiotic susceptibility. Clinical cases were included in the study if they showed signs of respiratory disease and data relating to bacterial culture and susceptibility of BALF samples were available. The medical records of 493 privately owned dogs that were presented between January 1989 and December 2011 were evaluated retrospectively. In 35 per cent of samples, no bacteria were cultured. Bacteria isolated from culture‐positive samples includedStreptococcusspecies (31 per cent of positive cultures), Enterobacteriaceae (30 per cent, includingEscherichia coli(15 per cent)),Staphylococcusspecies (19 per cent),Pasteurellaspecies (16 per cent) andPseudomonasspecies (14 per cent).Bordetella bronchisepticaas a primary respiratory pathogen was isolated in 8 per cent of cases. Enrofloxacin showed the best susceptibility pattern; 86 per cent of all isolates and 87 per cent of Gram‐negative bacteria were susceptible to this antibiotic. Amoxicillin/clavulanic acid yielded the best susceptibility pattern in Gram‐positive bacteria (92 per cent). Therefore, these antibiotics can be recommended for empirical or first‐line treatment in dogs with bacterial lower respiratory tract infections.
Ten‐minute chat
Authors: Huey Robert
Published: December 2014

Robert Huey qualified from Dublin vet school in 1983. He is Deputy Chief Veterinary Officer in the Department of Agriculture and Rural Development Northern Ireland (DARDNI) veterinary service.
SVS invites you to talk sheep
Authors: Thompson Dick
Published: December 2014

Dick Thompson describes an initiative which could help recent graduates without too much time on their hands to develop their interest in ovine medicine.
Time off and holidays
Authors:   BVA new graduate guide
Published: December 2014

Employees are entitled to a minimum of 28 days' paid holiday, including bank holidays, although some employers may offer more. These matters must be covered in your written statement of the terms and conditions of your employment and in your contract. In addition, other types of leave may also be available
Getting back up to speed
Authors:   BVA/RVC refresher days
Published: December 2014

Changing demographics in the veterinary profession mean that more people are taking career breaks. This year, the BVA is hosting a series of refresher days to help those returning to practice get back up to speed
Ten‐minute chat
Authors: Wolfensohn Simon
Published: December 2014

Simon Wolfensohn is the principal of a small animal practice in a rural town close to Swindon in Wiltshire. For almost 20 years he has divided his time between the practice and serving as a magistrate in Swindon. His other diversions from veterinary work are fly‐fishing, flying and running.
Ten‐minute chat
Authors: Wood James
Published: December 2014

James Wood is a veterinary epidemiologist working at Cambridge university and is the Alborada Professor of Equine and Farm Animal Science. His research interests are largely focused on zoonotic viral diseases, including mammalian influenza and potentially emergent viruses from bats, but he retains interests in a variety of other diseases, such as bovine tuberculosis, African horse sickness and bluetongue.
So you want to be a cattle vet?
Authors: Sibley Dick
Published: December 2014

The UK's two million dairy cows produce 14 billion litres of milk every year. Their milk is consumed by more than 95 per cent of the population every day in one form or another, and they contribute over 20 per cent of the entire agricultural output of the nation. They are precious indeed, and their health and welfare is paramount, says cattle vet Dick Sibley
Ten‐minute chat
Authors: Mills Daniel
Published: December 2014

Daniel Mills is professor of veterinary behavioural medicine at the University of Lincoln, where he leads the Masters course in clinical animal behaviour and an international research group examining companion animal behaviour and welfare.
Making good use of statistics
Authors: Shaw Darren
Published: December 2014

Statistics are just a tool to help you answer the questions you have set. It may sound obvious, but the clearer the questions you set, the easier it is to answer them says Darren Shaw, who offers some advice on the use of statistics in practice research projects
Working alongside the risk of rabies
Authors: Briner Jessica
Published: December 2014

Third‐year veterinary student Jessica Briner spent the Christmas holidays volunteering at the Bali Animal Welfare Association, giving her an opportunity to put what she had been learning at vet school into practice
From vet degree to vice‐president of R&D
Authors: Lightfoot‐Dunn Ruth
Published: December 2014

Ruth Lightfoot‐Dunn vividly remembers her first day at vet school, as it was ‘a huge milestone’ in her ambition to be a practising equine vet. Had someone told her at the time that her veterinary degree would lead to the role of vice‐president of R&D in the largest healthcare biotechnology company in the world, she would have insisted this would never happen. Here, she explains how it did
STRUCTURE AND MECHANICAL CHARACTERISTIC OF CATTLE HORNS
Authors: YU YONG-JUN , ZOU MENG , XU SHU-CAI , ZHANG RONG-RONG , WANG HUI-XIA , LIU JIAN-TAO
Published: December 2014

In order to investigate the structure and mechanical characteristics of cattle horns, the microstructures of the keratin shell and bone core were examined by scanning electron microscopy, and a series of mechanical tests were performed by the tension-compression test machine and pendulum impact test machine. Results showed that the keratin shell was a laminated structure stacked by keratin protein slices, and the bone core was a light-weight porous material with pores randomly distributed in the longitudinal direction. The ultimate tensile strength of the keratin shell diminished gradually from distal to middle to proximal parts with the values of 162, 125 and 85 MPa, respectively. The ultimate compressive strength of keratin shell and bone core in the longitudinal direction was higher than that in the transverse. The moisture could cut down significantly the mechanical characteristics of keratin shell and bone core. The shock toughness of the keratin shell was 4.9 J/cm2, which was 7 times as large as that of the bone core. It can be concluded that cattle horn is a graded biological material with outstanding mechanical characteristics. The moisture, location and direction of the sampling have a significant effect on the mechanical characteristics of cattle horns. Compared with the bone core, the keratin shell has a better crashworthiness performance.
Rotational dynamics of bases in the gene coding interferon alpha 17 (IFNA17)
Authors: Krasnobaeva L. A. , Yakushevich L. V.
Published: December 2014

In the present work, rotational oscillations of nitrogenous bases in the DNA with the sequence of the gene coding interferon alpha 17 (IFNA17), are investigated. As a mathematical model simulating oscillations of the bases, we use a system of two coupled nonlinear partial differential equations that takes into account effects of dissipation, action of external fields and dependence of the equation coefficients on the sequence of bases. We apply the methods of the theory of oscillations to solve the equations in the linear approach and to construct the dispersive curves determining the dependence of the frequency of the plane waves (ω) on the wave vector (q). In the nonlinear case, the solutions in the form of kink are considered, and the main characteristics of the kink: the rest energy (E0), the rest mass (m0), the size (d) and sound velocity (C0), are calculated. With the help of the energetic method, the kink velocity (υ), the path (S), and the lifetime (τ) are also obtained.
A self-adjoint decomposition of the radial momentum operator
Authors: Liu Q. H. , Xiao S. F.
Published: December 2014

With acceptance of the Dirac's observation that the canonical quantization entails using Cartesian coordinates, we examine the operator erPr rather than Pr itself and demonstrate that there is a decomposition of erPr into a difference of two self-adjoint but noncommutative operators, in which one is the total momentum and another is the transverse one. This study renders the operator Pr indirectly measurable and physically meaningful, offering an explanation of why the mean value of Pr over a quantum mechanical state makes sense and supporting Dirac's claim that Pr "is real and is the true momentum conjugate to r".
Effect of diagenetic recrystallization on the strength of planktonic foraminifer tests under compression
Authors: Pearson Paul N. , Evans Sam L. , Evans James
Published: December 2014

Abstract. We present the results of experiments to measure the brittle failure of fossil planktonic foraminifer tests under compression. We compare two upper Eocene species of contrasting morphology, Cribrohantkenina inflata (Howe, 1928) and Turborotalia cerroazulensis (Cole, 1928) in both well-preserved material from the Kilwa Group of Tanzania and recrystallized material from ODP Site 865, central Pacific Ocean. Well-preserved tests were several times stronger than recrystallized tests. Turborotalia cerroazulensis was stronger than C. inflata in both the well-preserved and recrystallized material.
A Pregnant Woman Who Underwent Laparoscopic Adrenalectomy due to Cushing’s Syndrome
Authors: Diri Halit , Bayram Fahri , Simsek Yasin , Ozkan Yusuf , Akcan Alper , Karahan Ibrahim , Ileri Ibrahim , Aribas Sulbiye , Koc Mehmet Sait
Published: December 2014

Cushing’s syndrome (CS) may lead to severe maternal and fetal morbidities and even mortalities in pregnancy. However, pregnancy complicates the diagnosis and treatment of CS. This study describes a 26-year-old pregnant woman admitted with hypertension-induced headache. Hormonal analyses performed due to her cushingoid phenotype revealed a diagnosis of adrenocorticotropic hormone- (ACTH-) independent CS. MRI showed a 3.5 cm adenoma in her right adrenal gland. After preoperative metyrapone therapy, she underwent a successful unilateral laparoscopic adrenalectomy at 14-week gestation. Although she had a temporary postoperative adrenal insufficiency, hormonal analyses showed that she has been in remission since delivery. Findings in this patient, as well as those in previous patients, indicate that pregnancy is not an absolute contraindication for laparoscopic adrenalectomy. Rather, such surgery should be considered a safe and efficient treatment method for pregnant women with cortisol-secreting adrenal adenomas.
Likelihood Inference of Nonlinear Models Based on a Class of Flexible Skewed Distributions
Authors: Chen Xuedong , Zeng Qianying , Song Qiankun
Published: December 2014

This paper deals with the issue of the likelihood inference for nonlinear models with a flexible skew-t-normal (FSTN) distribution, which is proposed within a general framework of flexible skew-symmetric (FSS) distributions by combining with skew-t-normal (STN) distribution. In comparison with the common skewed distributions such as skew normal (SN), and skew-t (ST) as well as scale mixtures of skew normal (SMSN), the FSTN distribution can accommodate more flexibility and robustness in the presence of skewed, heavy-tailed, especially multimodal outcomes. However, for this distribution, a usual approach of maximum likelihood estimates based on EM algorithm becomes unavailable and an alternative way is to return to the original Newton-Raphson type method. In order to improve the estimation as well as the way for confidence estimation and hypothesis test for the parameters of interest, a modified Newton-Raphson iterative algorithm is presented in this paper, based on profile likelihood for nonlinear regression models with FSTN distribution, and, then, the confidence interval and hypothesis test are also developed. Furthermore, a real example and simulation are conducted to demonstrate the usefulness and the superiority of our approach.
Treatments for Neurological Gait and Balance Disturbance: The Use of Noninvasive Electrical Brain Stimulation
Authors: Kaski Diego , Bronstein Adolfo M.
Published: December 2014

Neurological gait disorders are a common cause of falls, morbidity, and mortality, particularly amongst the elderly. Neurological gait and balance impairment has, however, proved notoriously difficult to treat. The following review discusses some of the first experiments to modulate gait and balance in healthy adults using anodal transcranial direct current stimulation (tDCS) by stimulating both cerebral hemispheres simultaneously. We review and discuss published data using this novel tDCS approach, in combination with physical therapy, to treat locomotor and balance disorders in patients with small vessel disease (leukoaraiosis) and Parkinson’s disease. Finally, we review the use of bihemispheric anodal tDCS to treat gait impairment in patients with stroke in the subacute phase. The findings of these studies suggest that noninvasive electrical stimulation techniques may be a useful adjunct to physical therapy in patients with neurological gait disorders, but further mutlicentre randomized sham-controlled studies are needed to evaluate whether experimental tDCS use can translate into mainstream clinical practice for the treatment of neurological gait disorders.
Ethnopharmacological Assessment of Medicinal Plants Used against Livestock Infections by the People Living around Indus River
Authors: Mussarat Sakina , Amber Rahila , Tariq Akash , Adnan Muhammad , AbdElsalam Naser M. , Ullah Riaz , Bibi Roqaia
Published: December 2014

The present study was aimed to document detailed ethnopharmacological knowledge of medicinal plants against livestock infections of an unexplored remote region of Pakistan. Semistructured questionnaires were used for data collection. Total 43 plants belonging to 26 families were found to be used in ethnoveterinary practices. Seeds (29%) were found to be the most frequent plant part used followed by leaves (22%). Ethnoveterinary recipes were mostly prepared in the form of decoction and powdering. Informant consensus factor (Fic) results revealed high consensus for gastrointestinal (0.81), mastitis (0.82), and dermatological infections (0.80).Curcuma longaranked first with highest fidelity level (FL) value (66%) followed byTrachyspermum ammithat ranked second (58%). Preference ranking (PR) results showed thatZingiber officinale,Punica granatum,Triticum aestivum,Gossypium hirsutum, andWithania coagulanswere the most preferred species for the treatment of diarrhea. Direct matrix ranking (DMR) results showed thatMorus alba,Melia azedarach,Withania coagulans,Cassia fistula,Azadirachta indica, andTamarix aphyllawere the multipurpose species of the region. We invite the attention of pharmacologists and chemists for further exploration of plants having high Fic, FL, and PR values in the present study. Conservation strategies should be adopted for the protection of multipurpose plant species.
Large Vessel Vasculitis Occurring in Rheumatoid Arthritis Patient under Anti-TNF Therapy
Authors: Cestelli Valentina , Spinella Amelia , Campomori Federica , Esposito Carmela , Ciaffi Sara , Sandri Gilda , Ferri Clodoveo
Published: December 2014

Vasculitis is a heterogeneous group of disorders characterized by the presence of necrotic inflammatory phenomena and destruction of blood vessels. Vasculitis is classified as primary (idiopathic) or secondary to infections, connective tissue diseases and drugs but can also be considered as a paraneoplastic phenomenon. Evidence shows that the increasing use of biological agents results in a growing number of reports of autoimmune diseases induced by these therapies. An inflammatory articular chronic disease such as rheumatoid arthritis may be complicated by extra-articular manifestations, such as cutaneous or systemic vasculitis. Herewith, we describe the case of a great vessels arteritis in a patient affected by rheumatoid arthritis in therapy with an anti-TNF agent (etanercept).
Microwave-Assisted Synthesis of Some 1,3,4-Oxadiazole Derivatives and Evaluation of Their Antibacterial and Antifungal Activity
Authors: Swarnkar Deepak , Ameta Rakshit , Vyas Ritu
Published: December 2014

A series of substituted 1,3,4-oxadiazole derivatives (3a–f) and (6a–f) have been synthesized from diphenylacetic acid hydrazide under microwave irradiation in various reaction conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, and 1H NMR. These targeted compounds have been tested for their antibacterial and antifungal activities compared to ampicillin and griseofulvin as standard drug. Compounds 3a, 3e, 3f, 6c, 6d, 6e, and 6d exhibited the maximum antibacterial activities while 3b, 3c, 3d, 3e, 6a, 6d, and 6e exhibited the maximum antifungal activities.
Accidental Coverage of Both Renal Arteries during Infrarenal Aortic Stent-Graft Implantation: Cause and Treatment
Authors: Bracale Umberto Marcello , Giribono Anna Maria , Vitale Gaetano , Narese Donatella , Santini Gianpaolo , del Guercio Luca
Published: December 2014

The purpose of this paper is to report a salvage maneuver for accidental coverage of both renal arteries during endovascular aneurysm repair (EVAR) of an infrarenal abdominal aortic aneurysm (AAA). A 72-year-old female with a 6 cm infrarenal abdominal aortic aneurysm was treated by endovascular means with a standard bifurcated graft. Upon completing an angiogram, both renal arteries were found to be accidentally occluded. Through a left percutaneous brachial approach, the right renal artery was catheterized and a chimney stent was deployed; however this was not possible for the left renal artery. A retroperitoneal surgical approach was therefore carried out with a retrograde chimney stent implanted to restore blood flow. After three months, both renal arteries were patent and renal function was not different from the baseline. Both endovascular with percutaneous access via the brachial artery and open retroperitoneal approaches with retrograde catheterization are feasible rescue techniques to recanalize the accidentally occluded renal arteries during EVAR.
Whole Genome Expression Profiling and Signal Pathway Screening of MSCs in Ankylosing Spondylitis
Authors: Li Yuxi , Wang Peng , Xie Zhongyu , Huang Lin , Yang Rui , Gao Liangbin , Tang Yong , Zhang Xin , Ye Jichao , Chen Keng , Cai Zhaopeng , Wu Yanfeng , Shen Huiyong
Published: December 2014

The pathogenesis of dysfunctional immunoregulation of mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) is thought to be a complex process that involves multiple genetic alterations. In this study, MSCs derived from both healthy donors and AS patients were cultured in normal media or media mimicking an inflammatory environment. Whole genome expression profiling analysis of 33,351 genes was performed and differentially expressed genes related to AS were analyzed by GO term analysis and KEGG pathway analysis. Our results showed that in normal media 676 genes were differentially expressed in AS, 354 upregulated and 322 downregulated, while in an inflammatory environment 1767 genes were differentially expressed in AS, 1230 upregulated and 537 downregulated. GO analysis showed that these genes were mainly related to cellular processes, physiological processes, biological regulation, regulation of biological processes, and binding. In addition, by KEGG pathway analysis, 14 key genes from the MAPK signaling and 8 key genes from the TLR signaling pathway were identified as differentially regulated. The results of qRT-PCR verified the expression variation of the 9 genes mentioned above. Our study found that in an inflammatory environment ankylosing spondylitis pathogenesis may be related to activation of the MAPK and TLR signaling pathways.
Development of a Provisional Model to Improve Transitional Care for Female Adolescents with a Rare Genital Malformation as an Example for Orphan Diseases
Authors: Simoes Elisabeth , Kronenthaler Andrea , Emrich Christine , Rieger Monika A. , Rall Kristin Katharina , Schäffeler Norbert , Hiltner Hanna , Ueding Esther , Brucker Sara Y.
Published: December 2014

Deficits of care exist during the transitional period, when young people with ongoing needs of support to achieve their physical, social, and psychological potential are entering adulthood. This study aims to develop a patient oriented, structured provisional model to improve transitional care for adolescents withMayer-Rokitansky-Kuester-Hauser-Syndromeas an example for orphan diseases, where problems of access and continuity are even more complex. The study is funded by the German Federal Ministry of Education and Research (BMBF-Funding Code 01GY1125). The target patient group are young females with this disorder, treated at the Centre for Rare Genital Malformations in Women (ZSGF), University Hospital of Tuebingen. The study comprises five phases: an appraisal of literature, assessment of patients (n=25), parents’, partners’, and health and social care providers’ (n=24) needs and experienced deficits in care and support in a qualitative approach, construction of a provisional model via scenario technique, followed by communicative validation (including interested public,n=100), preference finding, and identification of patient-oriented quality aims for follow-up. Quantitative data from questionnaires and chart review (as sociodemographic data, nonresponder analysis, and preference rating) are worked up for descriptive statistics. The results provide a platform for the development of future multidisciplinary transitional intervention programs in orphan diseases.
Regularity and Chaos in the Hydrogen Atom Highly Excited with a Strong Magnetic Field
Authors: Amdouni M. , Eleuch H.
Published: December 2014

The effects of the relativistic corrections on the energy spectra are analyzed. Effective simulations based on manipulations of operators in the Sturmian basis are developed. Discrete and continuous energy spectra of a hydrogen atom with realistic nucleus mass in a strong magnetic field are computed. The transition from regularity to chaos in diamagnetic problem with the effect of the nucleus recoil energy is explored. Anticrossing of energy levels is observed for strong magnetic field.
Double Barreled Wet Colostomy: Initial Experience and Literature Review
Authors: Salgado-Cruz Luis , Espin-Basany Eloy , Vallribera-Valls Francesc , Sanchez-Garcia Jose , Jimenez-Gomez Luis Miguel , Marti-Gallostra Marc , Garza-Maldonado Ana
Published: December 2014

Background. Pelvic exenteration and multivisceral resection in colorectal have been described as a curative and palliative intervention. Urinary tract reconstruction in a pelvic exenteration is achieved in most cases with an ileal conduit of Bricker, although different urinary reservoirs have been described.Methods. A retrospective and observational study of six patients who underwent a pelvic exenteration and urinary tract reconstruction with a double barreled wet colostomy (DBWC) was done, describing the preoperative diagnosis, the indication for the pelvic exenteration, the complications associated with the procedure, and the followup in a period of 5 years. A literature review of the case series reported of the technique was performed.Results. Six patients had a urinary tract reconstruction with the DBWC technique, 5 male patients and one female patient. Age range was from 20 to 77 years, with a medium age 53.6 years. The most frequent complication presented was a pelvic abscess in 3 patients (42.85%); all complications could be resolved with a conservative treatment.Conclusion. In the group of our patients with pelvic exenteration and urinary tract reconstruction with a DBWC, it is a safe procedure and well tolerated by the patients, and most of the complications can be resolved with conservative treatment.
Expanding Epigenomics to Archived FFPE Tissues: An Evaluation of DNA Repair Methodologies
Authors: Siegel Erin M. , Berglund Anders E. , Riggs Bridget M. , Eschrich Steven A. , Putney Ryan M. , Ajidahun Abidemi O. , Coppola Domenico , Shibata David
Published: December 2014

Background: Epigenome-wide association studies are emerging in the field of cancer epidemiology with the rapid development of large-scale methylation array platforms. Until recently, these methods were only valid for DNA from flash frozen (FF) tissues. Novel techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) tissues have emerged; however, a direct comparison of FFPE DNA repair methods before analysis on genome-wide methylation array to matched FF tissues has not been conducted.

Methods: We conducted a systematic performance comparison of two DNA repair methods (REPLI-g Ligase vs. Infinium HD Restore Kit) on FFPE-DNA compared with matched FF tissues on the Infinium 450K array. A threshold of discordant methylation between FF-FFPE pairs was set at Δβ > 0.3. The correlations of β-values from FF–FFPE pairs were compared across methods and experimental conditions.

Results: The Illumina Restore kit outperformed the REPLI-g ligation method with respect to reproducibility of replicates (R2 > 0.970), highly correlated β-values between FF-FFPE (R2 > 0.888), and fewest discordant loci between FF-FFPE (≤0.61%). The performance of the Restore kit was validated in an independent set of 121 FFPE tissues.

Conclusions: The Restore kit outperformed RELPI-g ligation in restoring FFPE-derived DNA before analysis on the Infinium 450K methylation array. Our findings provide critical guidance that may significantly enhance the breadth of diseases that can be studied by methylomic profiling.

Impact: Epigenomic studies using FFPE tissues should now be considered among cancers that have not been fully characterized from an epigenomic standpoint. These findings promote novel epigenome-wide studies focused on cancer etiology, identification of novel biomarkers, and developing targeted therapies.

See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”

Cancer Epidemiol Biomarkers Prev; 23(12); 2622–31. ©2014 AACR.
Methods for Sample Acquisition and Processing of Serial Blood and Tumor Biopsies for Multicenter Diffuse Large B-cell Lymphoma Clinical Trials
Authors: Nielsen Torsten Holm , Diaz Zuanel , Christodoulopoulos Rosa , Charbonneau Fredrick , Qureshi Samia , Rousseau Caroline , Benlimame Naciba , Camlioglu Errol , Constantin André Marc , Oros Kathleen Klein , Krumsiek Jan , Crump Michael , Morin Ryan D. , Cerchietti Leandro , Johnson Nathalie A. , Petrogiannis-Haliotis Tina , Miller Wilson H. , Assouline Sarit E. , Mann Koren K.
Published: December 2014

Increasingly, targeted therapies are being developed to treat malignancies. To define targets, determine mechanisms of response and resistance, and develop biomarkers for the successful investigation of novel therapeutics, high-quality tumor biospecimens are critical. We have developed standard operating procedures (SOPs) to acquire and process serial blood and tumor biopsies from patients with diffuse large B-cell lymphoma enrolled in multicenter clinical trials. These SOPs allow for collection and processing of materials suitable for multiple downstream applications, including immunohistochemistry, cDNA microarrays, exome sequencing, and metabolomics. By standardizing these methods, we control preanalytic variables that ensure high reproducibility of results and facilitate the integration of datasets from such trials. This will facilitate translational research, better treatment selection, and more rapid and efficient development of new drugs.

See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”

Cancer Epidemiol Biomarkers Prev; 23(12); 2688–93. ©2014 AACR.
Effects of Preanalytic Variables on Circulating MicroRNAs in Whole Blood
Authors: Zhao Hua , Shen Jie , Hu Qiang , Davis Warren , Medico Leonardo , Wang Dan , Yan Li , Guo Yuqing , Liu Biao , Qin Maochun , Nesline Mary , Zhu Qianqian , Yao Song , Ambrosone Christine B. , Liu Song
Published: December 2014

Research in the last decade suggests the clinical potential of circulating microRNAs in whole blood as biomarkers for cancer detection. However, before applying the identified circulating microRNAs clinically, biospecimen-focused research has to be performed to identify possible preanalytic variables that may significantly affect the levels of circulating microRNAs. In this study, using a unique resource of the Data Bank and BioRepository (DBBR) at Roswell Park Cancer Institute, we conducted a two-step analysis to identify internal control circulating microRNAs in whole blood and then to study how selected major preanalytic variables (namely, processing delay, storage condition, storage time, and freeze/thaw cycles) might affect the detection of circulating microRNAs. In the discovery phase of the first step, we identified three microRNAs, including miR346, miR134, and miR934, whose levels exhibited the smallest variation between the case–control groups, as well as within each group interindividually. In the further validation analysis, the consistency was validated for miR346 and miR134 but not for miR934. At the second step, using miR346 and miR134 as internal controls, we observed that as the numbers of freeze/thaw cycles increased, levels of both miR346 and miR134 were significantly decreased (Ptrend < 0.0001); varying other processing and storage conditions did not affect miRNA levels. In the paralleled analysis in plasma samples, levels of miR16 were significantly decreased by increasing processing delay and increasing numbers of freeze/thaw cycles but not affected by storage condition and duration. The results from this study highlight the necessity of biospecimen-focused research on circulating microRNAs before clinical utilization.

See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”

Cancer Epidemiol Biomarkers Prev; 23(12); 2643–8. ©2014 AACR.
Circulating Sex Hormones and Terminal Duct Lobular Unit Involution of the Normal Breast
Authors: Khodr Zeina G. , Sherman Mark E. , Pfeiffer Ruth M. , Gierach Gretchen L. , Brinton Louise A. , Falk Roni T. , Patel Deesha A. , Linville Laura M. , Papathomas Daphne , Clare Susan E. , Visscher Daniel W. , Mies Carolyn , Hewitt Stephen M. , Storniolo Anna Maria V. , Rosebrock Adrian , Caban Jesus J. , Figueroa Jonine D.
Published: December 2014

Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009–2011).

Methods: We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Ptrends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone–binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.

Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07–1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72–0.89; Ptrend < 0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32–1.97; Ptrend < 0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09–1.59; Ptrend = 0.0043) were associated with higher TDLU counts.

Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.

Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. Cancer Epidemiol Biomarkers Prev; 23(12); 2765–73. ©2014 AACR.
Predictive Value of the Combined p16INK4a and Ki-67 Immunocytochemistry in Low-Grade Squamous Intraepithelial Lesions
Authors: Ziemke Peter , Marquardt Katrin , Griesser Henrik
Published: December 2014

Objective: The reliability of cytological diagnoses, especially for low-grade squamous intraepithelial lesions (LSIL), is limited. This leads to uncertainty in patient management. The application of adjunctive biomarkers is meant to improve this situation. Therefore, we examined the prognostic value of p16/Ki-67 immunostaining of LSIL cytology specimens. Study Design: We analyzed the p16INK4a and Ki-67 immunocytochemistry (CINtec® PLUS, dual stain) of 260 patients with LSIL. Cytology and dual-stain results were correlated with histology at the time of treatment or with cytological follow-up. Results: After an average duration of 24.9 months (1-58) and a histology rate of 36.2% [cervical intraepithelial neoplasia, grade 2 or higher (CIN2+) as positive], the statistical evaluation for cytology and dual stain resulted in a sensitivity of 98.3 and 90.0%, respectively, a specificity of 74.5% for dual stain, a positive predictive value (PPV) of 22.8 and 51.4%, and a negative predictive value (NPV) of 96.1% for dual stain. Conclusion: The combined immunocytochemical investigation of p16INK4a and Ki-67 leads to a significantly better PPV and a very good NPV for CIN2+ in LSIL, especially in women 30 years of age and older. An objective individualized prognosis may not be achieved with p16INK4a/Ki-67. Statistical data from our study, however, indicate that patient management can be significantly improved by the application of combined p16/Ki-67 immunocytochemistry as an adjunct to cytology.
Multifocal Corneal Excimer Femtosecond Laser in situ Keratomileusis following Radial Keratotomy: A Case Report with Six Months of Follow-Up
Authors: Vastardis Iraklis , Gatzioufas Zisis , Eggspühler Pajic Brigitte , Müller Jörg , Pajic Bojan
Published: December 2014

We report the case of a 46-year-old female patient who was referred to our clinic (Orasis Eye Clinic, Reinach, Switzerland) seeking improvement of her distance and near visual acuity. Radial keratotomy (RK) was performed at a younger age on both eyes to correct -5 D myopia. The patient underwent a bilateral same-session multifocal corneal excimer femtosecond laser (Supracor) keratomileusis correction. We introduce a new correction approach, possibly suitable for presbyopic patients previously treated with RK, and we present several potential novel advantages such as enhanced near, intermediate vision, and improvement in quality of life. This is the first report of a bilateral excimer laser treatment attempt of presbyopia following RK.